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Morón-Ocaña JM, Muñoz-Morera S, Navarro-Gilabert Á, Martínez-Barranca ML, Coronel-Pérez IM, Pérez-Gil A. High-Potency Capsaicin Patches (8%): A Promising Option for Dermatoses Associated With Neuropathic Pain and Pruritus. Int J Dermatol 2025. [PMID: 40405384 DOI: 10.1111/ijd.17869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 04/13/2025] [Accepted: 05/14/2025] [Indexed: 05/24/2025]
Affiliation(s)
| | | | | | | | | | - Amalia Pérez-Gil
- Department of Dermatology, Virgen de Valme Hospital, Sevilla, Spain
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2
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Wang N, Zhou X, Zhang T, Jian W, Sun Z, Qi P, Feng Y, Liu H, Liu L, Yang S. Capsaicin from chili peppers and its analogues and their valued applications: An updated literature review. Food Res Int 2025; 208:116034. [PMID: 40263816 DOI: 10.1016/j.foodres.2025.116034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 10/24/2024] [Accepted: 02/21/2025] [Indexed: 04/24/2025]
Abstract
Chili peppers are widely sought after by consumers for not only their color, flavor, and nutritional properties but also their main component (capsaicin) various biological activities in diverse fields. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), the compound primarily responsible for the spicy flavor of peppers, remains a hot topic in the scientific community and shows the vast potential in various applications. Although many reviews focus comprehensively on capsaicin, most articles are limited to the medical field of capsaicin. This review provides an overview briefly of the capsaicin and its analogues in the fields of food, medicine and with a particular emphasis on their applications in agriculture and livestock farming. Overall, we aims is to expand the broad spectrum of applications for capsaicin and its analogues and explore their potential biological mechanisms. Finally, the challenges of capsaicin and future development prospects were discussed and proposed.
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Affiliation(s)
- Na Wang
- State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China.; Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China
| | - Xiang Zhou
- State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China..
| | - Taihong Zhang
- State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China
| | - Wujun Jian
- State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China
| | - Zhaoju Sun
- State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China
| | - Puying Qi
- State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China
| | - Yumei Feng
- State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China
| | - Hongwu Liu
- State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China
| | - Liwei Liu
- State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China
| | - Song Yang
- State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China..
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Wu J, Hu H, Li X. Spinal neuron-glial crosstalk and ion channel dysregulation in diabetic neuropathic pain. Front Immunol 2025; 16:1480534. [PMID: 40264787 PMCID: PMC12011621 DOI: 10.3389/fimmu.2025.1480534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 03/19/2025] [Indexed: 04/24/2025] Open
Abstract
Diabetic neuropathic pain (DNP) is one of the most prevalent complications of diabetes, characterized by a high global prevalence and a substantial affected population with limited effective therapeutic options. Although DNP is closely associated with hyperglycemia, an increasing body of research suggests that elevated blood glucose levels are not the sole inducers of DNP. The pathogenesis of DNP is intricate, involving the release of inflammatory mediators, alterations in synaptic plasticity, demyelination of nerve fibers, and ectopic impulse generation, yet the precise mechanisms remain to be elucidated. The spinal dorsal horn coordinates dynamic interactions between peripheral and central pain pathways, wherein dorsal horn neurons, microglia, and astrocytes synergize with Schwann cell-derived signals to process nociceptive information flow. Abnormally activated neurons can alter signal transduction by modifying the local microenvironment, compromising myelin integrity, and diminishing trophic support, leading to neuronal sensitization and an amplifying effect on peripheral pain signals, which in turn triggers neuropathic pain. Ion channels play a pivotal role in signal conduction, with the modulation of sodium, potassium, and calcium channels being particularly crucial for the regulation of pain signals. In light of the rising incidence of diabetes and the current scarcity of effective DNP treatments, a thorough investigation into the interactions between neurons and glial cells, especially the mechanisms of ion channel function in DNP, is imperative for identifying potential drug targets, developing novel therapeutic strategies, and thereby enhancing the prospects for DNP management.
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Affiliation(s)
- Jie Wu
- Department of Anesthesiology, The 2 Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
- Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang, Jiangxi, China
| | - Haijun Hu
- Department of Anesthesiology, The 2 Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
- Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang, Jiangxi, China
| | - Xi Li
- Department of Anesthesiology, The 2 Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
- Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang, Jiangxi, China
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Liu J, Zhang D. Cytochrome P450-mediated carbon-carbon bond formation in drug metabolism. Drug Metab Rev 2025; 57:51-66. [PMID: 39906921 DOI: 10.1080/03602532.2025.2451847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 01/06/2025] [Indexed: 02/06/2025]
Abstract
Cytochrome P450 (CYPs) enzymes are essential for the metabolism of numerous drug compounds and are capable of catalyzing many types of biotransformation reactions. One of the more unusual reactions catalyzed by CYPs is carbon-carbon (C-C) bond formation, which is critical in organic synthesis but found less commonly in nature. This review focuses on examples of C-C bond formation that occur during drug metabolism and highlights the mechanism for the formation of novel drug metabolites that result from these reactions. The different roles that mammalian CYPs can play in C-C bond formations are also discussed in detail. Ultimately, an understanding of the range of xenobiotics that undergo C-C bond formation and the mechanisms by which they do so can further facilitate metabolite identification and drug design efforts.
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Affiliation(s)
- Joyce Liu
- Department of Drug Metabolism and Pharmacokinetics, Genentech, Inc, South San Francisco, CA, USA
| | - Donglu Zhang
- Department of Drug Metabolism and Pharmacokinetics, Genentech, Inc, South San Francisco, CA, USA
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Fu M, Zhu J. The roles of TRPV1 receptors in nervous system with a special emphasis on sleep and memory. Neuroscience 2025; 565:589-593. [PMID: 39626824 DOI: 10.1016/j.neuroscience.2024.11.080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 11/16/2024] [Accepted: 11/30/2024] [Indexed: 12/28/2024]
Abstract
Transient receptor vanillin 1 (TRPV1) is widely expressed in the neural axis and surrounding tissues, and is easily activated by harmful stimuli such as pain and inflammatory responses. Previous studies have shown that activated TRPV1 channels regulate all levels of nervous system activity by improving calcium influx and modulating nervous system excitability. Recent studies have suggested that TRPV1 activation in the peripheral nervous system may induce sleep disorders, while activation in the central nervous system may ameliorate sleep disorders and assist memory consolidation processes. Here, we summarize the risk factors for inducing sleep disorders, the alteration of these risk factors by TRPV1 receptor activation, and the driving effect of TRPV1 receptor activity on memory consolidation.
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Affiliation(s)
- Ming Fu
- Shengjing Hospital of China Medical University, China
| | - JunChao Zhu
- Shengjing Hospital of China Medical University, China.
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Fang Q, Yu L, Tian F, Chen W, Zhai Q, Zhang H. Randomized controlled trials of the effects of capsaicin or menthol on irritable bowel syndrome: a systematic review and meta-analysis. Food Funct 2024; 15:11865-11874. [PMID: 39576289 DOI: 10.1039/d4fo04268a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/10/2024]
Abstract
Irritable bowel syndrome (IBS) is a common intestinal disease characterized by abdominal pain, abdominal distension and irregular defecation frequency, and it has had a high incidence and low cure rate in recent years. Visceral hypersensitivity (VH) is one of the main physiological indicators of IBS, and TRPV1 and TRPM8 (transient receptor potential vanilloid 1 and melastatin 8) play crucial roles in VH and are widely distributed in the intestine, significantly impacting abdominal pain in IBS patients. Under the guidance of PRISMA, four databases were systematically searched at the outset, including PubMed, Web of Science, Embase, and Cochrane Library. Randomized controlled trials (RCTs) reporting specific abdominal pain scores (rather than the incidence rate) in IBS patients receiving capsaicin or menthol (agonist of TRPV1 and TRPM8) interventions were included. A meta-analysis was conducted on the retrieved studies, which consisted of three articles on capsaicin and five articles on menthol, to compare the efficacy of capsaicin and menthol in alleviating abdominal pain in IBS patients under conditions of low heterogeneity. The results demonstrated that menthol had a significant effect in relieving abdominal pain in IBS patients. Conversely, although the effect of capsaicin was not statistically significant, two studies involving long-term capsaicin intervention suggested its potential to reduce VH and subsequently relieve abdominal pain, which may be attributed to the up-regulation of the TRPV1 receptor in the gastrointestinal tract of individuals with IBS.
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Affiliation(s)
- Qingying Fang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China.
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China
| | - Leilei Yu
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China.
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China
| | - Fengwei Tian
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China.
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China
| | - Wei Chen
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China.
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China.
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China
| | - Hao Zhang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China.
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China
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Kool D, Hoeijmakers JG, Waxman SG, Faber CG. Small fiber neuropathy. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2024; 179:181-231. [PMID: 39580213 DOI: 10.1016/bs.irn.2024.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2024]
Abstract
Small fiber neuropathy (SFN) is a condition involving the small nerve fibers of the peripheral nervous system, specifically the thinly myelinated Aδ and unmyelinated C fibers. It is an increasingly acknowledged condition within the spectrum of neuropathic pain disorders, leading to a rise in diagnosed patients. SFN is characterized by neuropathic pain, that is often described as burning, and typically presents in the hands and feet ascending proximally. Since small nerve fibers are involved in the autonomic nervous system, SFN can also lead to autonomic dysfunction. In the clinical setting, SFN diagnosis is frequently based on the Besta Criteria, which include skin biopsy and quantitative sensory testing. For clinical trials, the ACTTION criteria are also recommended. However, the diagnostic process is often complex, prompting research towards more accessible diagnostic methods. The pathophysiology of SFN remains unclear, thereby challenging therapeutic strategies. A large variety of underlying conditions has been associated with SFN, including metabolic, immune-mediated, infectious, toxic and hereditary conditions. The discovery of genetic sodium channelopathies in SFN provides insight into its underlying mechanisms. Newly discovered mutations within these genes reveal that SFN often shows overlapping clinical presentations with other sodium channelopathies. This chapter provides an in-depth look at SFN, including its clinical features, diagnostic methods, underlying conditions and possible therapeutic strategies.
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Affiliation(s)
- Dennis Kool
- Department of Neurology, Mental Health and Neuroscience Research Institute, Maastricht University Medical Center+, Maastricht, Netherlands.
| | - Janneke Gj Hoeijmakers
- Department of Neurology, Mental Health and Neuroscience Research Institute, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Stephen G Waxman
- Department of Neurology, Yale University School of Medicine, New Haven, CT, United States; Center for Neuroscience & Regeneration Research, Yale University, West Haven, CT, United States; Neuro-Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, United States
| | - Catharina G Faber
- Department of Neurology, Mental Health and Neuroscience Research Institute, Maastricht University Medical Center+, Maastricht, Netherlands
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Gao N, Li M, Wang W, Liu Z, Guo Y. The dual role of TRPV1 in peripheral neuropathic pain: pain switches caused by its sensitization or desensitization. Front Mol Neurosci 2024; 17:1400118. [PMID: 39315294 PMCID: PMC11417043 DOI: 10.3389/fnmol.2024.1400118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 08/12/2024] [Indexed: 09/25/2024] Open
Abstract
The transient receptor potential vanilloid 1 (TRPV1) channel plays a dual role in peripheral neuropathic pain (NeuP) by acting as a "pain switch" through its sensitization and desensitization. Hyperalgesia, commonly resulting from tissue injury or inflammation, involves the sensitization of TRPV1 channels, which modulates sensory transmission from primary afferent nociceptors to spinal dorsal horn neurons. In chemotherapy-induced peripheral neuropathy (CIPN), TRPV1 is implicated in neuropathic pain mechanisms due to its interaction with ion channels, neurotransmitter signaling, and oxidative stress. Sensitization of TRPV1 in dorsal root ganglion neurons contributes to CIPN development, and inhibition of TRPV1 channels can reduce chemotherapy-induced mechanical hypersensitivity. In diabetic peripheral neuropathy (DPN), TRPV1 is involved in pain modulation through pathways including reactive oxygen species and cytokine production. TRPV1's interaction with TRPA1 channels further influences chronic pain onset and progression. Therapeutically, capsaicin, a TRPV1 agonist, can induce analgesia through receptor desensitization, while TRPV1 antagonists and siRNA targeting TRPV1 show promise in preclinical studies. Cannabinoid modulation of TRPV1 provides another potential pathway for alleviating neuropathic pain. This review summarizes recent preclinical research on TRPV1 in association with peripheral NeuP.
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Affiliation(s)
- Ning Gao
- Department of Acupuncture and Moxibustion, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Meng Li
- Department of Gastroenterology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Weiming Wang
- Department of Acupuncture and Moxibustion, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zhen Liu
- Department of Gastroenterology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yufeng Guo
- Department of Acupuncture and Moxibustion, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Cheng XL, Ruan YL, Dai JY, Fan HZ, Ling JY, Chen J, Lu WG, Gao XJ, Cao P. 8-shogaol derived from dietary ginger alleviated acute and inflammatory pain by targeting TRPV1. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 128:155500. [PMID: 38484627 DOI: 10.1016/j.phymed.2024.155500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 01/24/2024] [Accepted: 02/26/2024] [Indexed: 05/01/2024]
Abstract
Ginger, a well-known spice plant, has been used widely in medicinal preparations for pain relief. However, little is known about its analgesic components and the underlying mechanism. Here, we ascertained, the efficacy of ginger ingredient 8-Shogaol (8S), on inflammatory pain and tolerance induced by morphine, and probed the role of TRPV1 in its analgesic action using genetic and electrophysiology approaches. Results showed that 8S effectively reduced nociceptive behaviors of mice elicited by chemical stimuli, noxious heat as well as inflammation, and antagonized morphine analgesic tolerance independent on opioid receptor function. Genetic deletion of TRPV1 significantly abolished 8S' analgesia action. Further calcium imaging and patch-clamp recording showed that 8S could specifically activate TRPV1 in TRPV1-expressing HEK293T cells and dorsal root ganglion (DRG) neurons. The increase of [Ca2+]i in DRG was primarily mediated through TRPV1. Mutational and computation studies revealed the key binding sites for the interactions between 8S and TRPV1 included Leu515, Leu670, Ile573, Phe587, Tyr511, and Phe591. Further studies showed that TRPV1 activation evoked by 8S resulted in channel desensitization both in vitro and in vivo, as may be attributed to TRPV1 degradation or TRPV1 withdrawal from the cell surface. Collectively, this work provides the first evidence for the attractive analgesia of 8S in inflammatory pain and morphine analgesic tolerance mediated by targeting pain-sensing TRPV1 channel. 8S from dietary ginger has potential as a candidate drug for the treatment of inflammatory pain.
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Affiliation(s)
- Xiao-Lan Cheng
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Hongshan Road, Nanjing 210028, China; School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yong-Lan Ruan
- Department of Neurology, Changzhou Hospital Affiliated to Nanjing University of Chinese Medicine, Changzhou, 213003, China
| | - Jing-Ya Dai
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Hongshan Road, Nanjing 210028, China; Wanbei Health Vocational College, Suzhou, Anhui, 234000, China
| | - Hai-Zhen Fan
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Hongshan Road, Nanjing 210028, China
| | - Jin-Ying Ling
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Hongshan Road, Nanjing 210028, China
| | - Jiao Chen
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Hongshan Road, Nanjing 210028, China
| | - Wu-Guang Lu
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Hongshan Road, Nanjing 210028, China
| | - Xue-Jiao Gao
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Hongshan Road, Nanjing 210028, China.
| | - Peng Cao
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Hongshan Road, Nanjing 210028, China; The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, 100 Minjiang Road, Quzhou, Zhejiang 324000, China.
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Hu Q, Liu H, Wang R, Yao L, Chen S, Wang Y, Lv C. Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway. J Inflamm Res 2024; 17:153-170. [PMID: 38223422 PMCID: PMC10787572 DOI: 10.2147/jir.s441141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 01/03/2024] [Indexed: 01/16/2024] Open
Abstract
Purpose Acute lung injury (ALI) is a severe pulmonary disease characterized by damage to the alveoli and pulmonary blood vessels, leading to severe impairment of lung function. Studies on the effect of capsaicin (8-methyl-N-geranyl-6-nonamide, CAP) on lipopolysaccharide (LPS)-induced ALI in bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B) are still limited. This study aimed to investigate the effect and specific mechanism by which CAP improves LPS-induced ALI. Methods The present study investigated the effect of CAP and the potential underlying mechanisms in LPS-induced ALI in vitro and vivo via RNA sequencing, Western blotting (WB), quantitative real-time reverse transcription PCR (qRT‒PCR), enzyme-linked immunosorbent assay (ELISA), and transmission electron microscopy (TEM). The TRPV1 inhibitor AMG9810 and the AKT agonist SC79 were used to confirm the protective effect of the TRPV1/AKT axis against ALI. The autophagy agonist rapamycin (Rapa) and the autophagy inhibitors 3-methyladenine (3-MA) and bafilomycin A1 (Baf-A1) were used to clarify the characteristics of LPS-induced autophagy. Results Our findings demonstrated that CAP effectively suppressed inflammation and autophagy in LPS-induced ALI, both in vivo and in vitro. This mechanism involves regulation by the TRPV1/AKT signaling pathway. By activating TRPV1, CAP reduces the expression of P-AKT, thereby exerting its anti-inflammatory and inhibitory effects on pro-death autophagy. Furthermore, prior administration of CAP provided substantial protection to mice against ALI induced by LPS, reduced the lung wet/dry ratio, decreased proinflammatory cytokine expression, and downregulated LC3 expression. Conclusion Taken together, our results indicate that CAP protects against LPS-induced ALI by inhibiting inflammatory responses and autophagic death through the TRPV1/AKT signaling pathway, presenting a novel strategy for ALI therapy.
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Affiliation(s)
- Qin Hu
- Emergency and Trauma College, Hainan Medical University, Haikou, People’s Republic of China
- Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Haikou, People’s Republic of China
| | - Haoran Liu
- Emergency and Trauma College, Hainan Medical University, Haikou, People’s Republic of China
- Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Haikou, People’s Republic of China
| | - Ruiyu Wang
- Emergency Medicine Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Li Yao
- Emergency Medicine Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Shikun Chen
- Department of Anesthesiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Yang Wang
- Emergency Medicine Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Chuanzhu Lv
- Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Haikou, People’s Republic of China
- Emergency Medicine Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
- Research Unit of Island Emergency Medicine, Chinese Academy of Medical Sciences (No. 2019RU013), Hainan Medical University, Haikou, People’s Republic of China
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Satapathy T, Singh G, Pandey RK, Shukla SS, Bhardwaj SK, Gidwani B. Novel Targets and Drug Delivery System in the Treatment of Postoperative Pain: Recent Studies and Clinical Advancement. Curr Drug Targets 2024; 25:25-45. [PMID: 38037995 DOI: 10.2174/0113894501271207231127063431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Revised: 10/18/2023] [Accepted: 11/07/2023] [Indexed: 12/02/2023]
Abstract
Pain is generated by a small number of peripheral targets. These can be made more sensitive by inflammatory mediators. The number of opioids prescribed to the patients can be reduced dramatically with better pain management. Any therapy that safely and reliably provides extended analgesia and is flexible enough to facilitate a diverse array of release profiles would be useful for improving patient comfort, quality of care, and compliance after surgical procedures. Comparisons are made between new and traditional methods, and the current state of development has been discussed; taking into account the availability of molecular and cellular level data, preclinical and clinical data, and early post-market data. There are a number of benefits associated with the use of nanotechnology in the delivery of analgesics to specific areas of the body. Nanoparticles are able to transport drugs to inaccessible bodily areas because of their small molecular size. This review focuses on targets that act specifically or primarily on sensory neurons, as well as inflammatory mediators that have been shown to have an analgesic effect as a side effect of their anti- inflammatory properties. New, regulated post-operative pain management devices that use existing polymeric systems were presented in this article, along with the areas for potential development. Analgesic treatments, both pharmacological and non-pharmacological, have also been discussed.
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Affiliation(s)
- Trilochan Satapathy
- Department of Pharmacology, Columbia Institute of Pharmacy, Raipur, Chhattisgarh-493111, India
| | - Gulab Singh
- Department of Pharmacology, Columbia Institute of Pharmacy, Raipur, Chhattisgarh-493111, India
| | - Ravindra Kumar Pandey
- Department of Pharmacology, Columbia Institute of Pharmacy, Raipur, Chhattisgarh-493111, India
| | - Shiv Shankar Shukla
- Department of Pharmacology, Columbia Institute of Pharmacy, Raipur, Chhattisgarh-493111, India
| | - Shiv Kumar Bhardwaj
- Department of Pharmacology, Columbia Institute of Pharmacy, Raipur, Chhattisgarh-493111, India
| | - Beena Gidwani
- Department of Pharmacology, Columbia Institute of Pharmacy, Raipur, Chhattisgarh-493111, India
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Dutta D, Tripathi D, Asthana P, Rana K, Jain N, Sharma R, Naithani U, Jauhari D, Rachana. Therapeutic Effects of Capsaicin on Central Nervous Disorders with Special Emphasis on Parkinson’s and Alzheimer’s Diseases. CAPSAICINOIDS 2024:489-510. [DOI: 10.1007/978-981-99-7779-6_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Landrum O, Marcondes L, Egharevba T, Gritsenko K. Painful diabetic peripheral neuropathy of the feet: integrating prescription-strength capsaicin into office procedures. Pain Manag 2023; 13:613-626. [PMID: 37750226 DOI: 10.2217/pmt-2023-0028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/27/2023] Open
Abstract
Prescription-strength (8%) capsaicin topical system is a US FDA-approved treatment for painful diabetic peripheral neuropathy of the feet. A 30 min application of the capsaicin 8% topical system can provide sustained (up to 3 months) local pain relief by desensitizing and reducing TRPV1-expressing cutaneous fibers. Capsaicin is not absorbed systemically; despite associated application-site discomfort, capsaicin 8% topical system is well tolerated, with no known drug interactions or contraindications, and could offer clinical advantages over oral options. Capsaicin 8% topical system are not for patient self-administration and require incorporation into office procedures, with the added benefit of treatment compliance. This article reviews existing literature and provides comprehensive, practical information regarding the integration of capsaicin 8% topical systems into office procedures.
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Affiliation(s)
- Orlando Landrum
- Regenerative Medicine & Interventional Pain Specialist, Cutting Edge Integrative Pain Centers, 3060 Windsor Cir, Elkhart, IN 46514, USA
| | - Lizandra Marcondes
- Averitas Pharma, Inc., Morristown, 360 Mt Kemble Ave, Morristown, NJ 07960, USA
| | - Toni Egharevba
- Averitas Pharma, Inc., Morristown, 360 Mt Kemble Ave, Morristown, NJ 07960, USA
| | - Karina Gritsenko
- Montefiore Medical Center, New 111 E 210th St, Bronx, NY 10467, USA
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Oz M, Lorke DE, Howarth FC. Transient receptor potential vanilloid 1 (TRPV1)-independent actions of capsaicin on cellular excitability and ion transport. Med Res Rev 2023. [PMID: 36916676 DOI: 10.1002/med.21945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 01/17/2023] [Accepted: 02/26/2023] [Indexed: 03/15/2023]
Abstract
Capsaicin is a naturally occurring alkaloid derived from chili pepper that is responsible for its hot pungent taste. Capsaicin is known to exert multiple pharmacological actions, including analgesia, anticancer, anti-inflammatory, antiobesity, and antioxidant effects. The transient receptor potential vanilloid subfamily member 1 (TRPV1) is the main receptor mediating the majority of the capsaicin effects. However, numerous studies suggest that the TRPV1 receptor is not the only target for capsaicin. An increasing number of studies indicates that capsaicin, at low to mid µM ranges, not only indirectly through TRPV1-mediated Ca2+ increases, but also directly modulates the functions of voltage-gated Na+ , K+ , and Ca2+ channels, as well as ligand-gated ion channels and other ion transporters and enzymes involved in cellular excitability. These TRPV1-independent effects are mediated by alterations of the biophysical properties of the lipid membrane and subsequent modulation of the functional properties of ion channels and by direct binding of capsaicin to the channels. The present study, for the first time, systematically categorizes this diverse range of non-TRPV1 targets and discusses cellular and molecular mechanisms mediating TRPV1-independent effects of capsaicin in excitable, as well as nonexcitable cells.
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Affiliation(s)
- Murat Oz
- Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, Safat, Kuwait
| | - Dietrich E Lorke
- Department of Anatomy and Cellular Biology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates.,Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Frank C Howarth
- Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
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15
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Hans GH, Almeshal D, Vanlommel L, Roelant E, Verhaegen I, Smits E, Van Boxem K, Fontaine R, Investigators Team TPELICAN. Considerations on the Obstacles That Lead to Slow Recruitment in a Pain Management Clinical Trial: Experiences from the Belgian PELICAN (PrEgabalin Lidocaine Capsaicin Neuropathic Pain) Pragmatic Study. Pain Res Manag 2023; 2023:7708982. [PMID: 37089721 PMCID: PMC10121349 DOI: 10.1155/2023/7708982] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 03/05/2023] [Accepted: 03/29/2023] [Indexed: 04/25/2023]
Abstract
Background A qualitative evaluation study of the prematurely terminated PrEgabalin Lidocaine Capsaicin Neuropathic Pain (PELICAN) study was performed. The PELICAN study aimed to examine pain management for localized neuropathic pain (LNP), as epidemiological figures have shown a high percentage of LNP patients in Belgium. The study compared systemic and topical medications according to pain relief, adverse effects, and several measures of quality of life. Objective Achieving better study patient recruitment through qualitative research. To investigate and determine the causes of the observed recruitment problems in the PELICAN study, pain centers involved in the study as well as nonrecruiting pain centers were included. Furthermore, it aimed to highlight the positive and negative lessons learned from the conducted study and the number of obstacles the team had to overcome. Methods A qualitative study, using a mixed methods approach, was performed. Multiple pain centers in Belgium completed an online survey, after which a structured interview was conducted to elaborate the responses in more detail. The broad topics of these meetings were feedback about the study, reviewing survey answers, and actions undertaken to enhance recruitment. Results Different factors contributed to the low recruitment rate in the PELICAN study, such as limited and late referral from the general practitioners to the Belgian pain centers, insufficient internal referrals from nonpain specialists, lack of specific expertise on LNP in some centers, scarcity of staff, limited reimbursement to administer complex analgesic schemes, overestimation of the patient population, and the reluctance of patients to participate in pain research. Additionally, shortcomings in the implemented study design and the need for more logistical investments were identified. Conclusion The findings of the qualitative study demonstrate the need for further, more varied LNP research in Belgium, not limited to pharmacological studies. It also sheds important light on the recruitment obstacles that may be faced during these studies. Future studies could support this research by offering better proposals for feasibility and recruitment, for instance, by designing and conducting a compelling pilot study or applying social media during the recruitment phase. Clinical Trials. This trial is registered with NCT03348735. EUDRACT number 2018-003617-17.
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Affiliation(s)
- Guy H. Hans
- Multidisciplinary Pain Center, Antwerp University Hospital (UZA), Edegem, Belgium
- ASTARC, University of Antwerp (UA), Antwerp, Belgium
| | - Dima Almeshal
- Clinical Trial Center (CTC), Antwerp University Hospital (UZA), Edegem, Belgium
| | - Lotte Vanlommel
- Clinical Trial Center (CTC), Antwerp University Hospital (UZA), Edegem, Belgium
| | - Ella Roelant
- Clinical Trial Center (CTC), Antwerp University Hospital (UZA), Edegem, Belgium
- StatUa, Center for Statistics, University of Antwerp (UA), Antwerp, Belgium
| | - Iris Verhaegen
- Clinical Trial Center (CTC), Antwerp University Hospital (UZA), Edegem, Belgium
| | - Elke Smits
- Clinical Trial Center (CTC), Antwerp University Hospital (UZA), Edegem, Belgium
| | - Koen Van Boxem
- Department of Anesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Therapy, Hospital Oost-Limburg, Genk, Belgium
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Boden A, Lusque A, Lodin S, Bourgouin M, Mauries V, Moreau C, Fabre A, Mounier M, Poublanc M, Caunes-Hilary N, Filleron T. Study protocol of the TEC-ORL clinical trial: a randomized comparative phase II trial investigating the analgesic activity of capsaicin vs Laroxyl in head and neck Cancer survivors presenting with neuropathic pain sequelae. BMC Cancer 2022; 22:1260. [PMID: 36471253 PMCID: PMC9720988 DOI: 10.1186/s12885-022-10348-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 11/19/2022] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Neuropathic pain is common in cancer survivorship and is one of the most distressing symptoms for patients previously treated for head and neck cancer. Persistent neuropathic pain, when it is ongoing and uncontrolled, has a detrimental effect and erodes patients' quality of life. Patients treated for head and neck cancer are chronic opioid users to manage their post-treatment pain, which may entail an increased risk of addiction and overdose. We propose to evaluate the analgesic activity of high-concentration capsaicin patches for the treatment of head and neck cancer survivors presenting with neuropathic pain sequelae. METHODS TEC-ORL is a parallel, multicenter randomized comparative phase II study evaluating whether Capsaïcin patches (Qutenza®) reduce neuropathic pain when compared to Amitriptyline (Laroxyl®) in head and neck cancer survivors presenting with neuropathic pain sequelae. The primary efficacy outcome is the rate of patients with a pain reduction of at least two points at 9 months compared to baseline. Assuming that 5% of patients become lost to follow-up, 130 patients will need to be randomized to detect a 25% improvement (i.e., standard: 25%, experimental: 50%) using a one-sided chi-square test with an alpha of 0.05%. According to the recommendations for comparative phase II trials, the target differences and type I error rates are relaxed. Randomized patients will either be treated with a capsaicin 8% (Qutenza®) patch applied at three time intervals in the experimental arm or with Amitriptyline (Laroxyl®) (oral solution 40 mg/ml) taken for 9 months at the recommended daily dose of 25 mg to 75 mg in the control arm. DISCUSSION TEC-ORL is a randomized comparative phase II trial designed to comprehensively evaluate the analgesic activity of capsaicin compared to Laroxyl in Head and Neck Cancer survivors presenting with neuropathic pain sequelae. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT04704453 Date of registration: 2021/01/13.
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Affiliation(s)
- Antoine Boden
- Support Care Department, Institut Claudius Regaud IUCT-Oncopole, 1 avenue Irène Joliot Curie, 31059 Toulouse Cedex, France
| | - Amélie Lusque
- Biostatistics & Health Data Science Unit, Institut Claudius Regaud, IUCT-Oncopole, 1 avenue Irène Joliot Curie, 31059 Toulouse, France
| | - Sabrina Lodin
- Clinical Trials Office, Institut Claudius Regaud, IUCT-Oncopole, 1 avenue Irène Joliot Curie, 31059 Toulouse, France
| | - Marie Bourgouin
- Support Care Department, Institut Claudius Regaud IUCT-Oncopole, 1 avenue Irène Joliot Curie, 31059 Toulouse Cedex, France
| | - Valérie Mauries
- Support Care Department, Institut Claudius Regaud IUCT-Oncopole, 1 avenue Irène Joliot Curie, 31059 Toulouse Cedex, France
| | - Christelle Moreau
- Biostatistics & Health Data Science Unit, Institut Claudius Regaud, IUCT-Oncopole, 1 avenue Irène Joliot Curie, 31059 Toulouse, France
| | - Amandine Fabre
- Clinical Trials Office, Institut Claudius Regaud, IUCT-Oncopole, 1 avenue Irène Joliot Curie, 31059 Toulouse, France
| | - Muriel Mounier
- Clinical Trials Office, Institut Claudius Regaud, IUCT-Oncopole, 1 avenue Irène Joliot Curie, 31059 Toulouse, France
| | - Muriel Poublanc
- Clinical Trials Office, Institut Claudius Regaud, IUCT-Oncopole, 1 avenue Irène Joliot Curie, 31059 Toulouse, France
| | - Nathalie Caunes-Hilary
- Support Care Department, Institut Claudius Regaud IUCT-Oncopole, 1 avenue Irène Joliot Curie, 31059 Toulouse Cedex, France
| | - Thomas Filleron
- Biostatistics & Health Data Science Unit, Institut Claudius Regaud, IUCT-Oncopole, 1 avenue Irène Joliot Curie, 31059 Toulouse, France
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17
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Lim S, Seo SE, Jo S, Kim KH, Kim L, Kwon OS. Highly Efficient Real-Time TRPV1 Screening Methodology for Effective Drug Candidates. ACS OMEGA 2022; 7:36441-36447. [PMID: 36278091 PMCID: PMC9583638 DOI: 10.1021/acsomega.2c04202] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 09/21/2022] [Indexed: 05/26/2023]
Abstract
Transient receptor potential vanilloid 1 (TRPV1) agonists that bind to the vanilloid pocket are being actively studied in the pharmaceutical industry to develop novel treatments for chronic pain and cancer. To discover synthetic vanilloids without the side effect of capsaicin, a time-consuming process of drug candidate selection is essential to a myriad of chemical compounds. Herein, we propose a novel approach to field-effect transistors for the fast and facile screening of lead vanilloid compounds for the development of TRPV1-targeting medications. The graphene field-effect transistor was fabricated with human TRPV1 receptor protein as the bioprobe, and various analyses (SEM, Raman, and FT-IR) were utilized to verify successful manufacture. Simulations of TRPV1 with capsaicin, olvanil, and arvanil were conducted using AutoDock Vina/PyMOL to confirm the binding affinity. The interaction of the ligands with TRPV1 was detected via the fabricated platform, and the collected responses corresponded to the simulation analysis.
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Affiliation(s)
- Seong
Gi Lim
- Infectious
Disease Research Center, Korea Research
Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea
| | - Sung Eun Seo
- Infectious
Disease Research Center, Korea Research
Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea
- Department
of Civil and Environmental Engineering, Yonsei University, Seoul 03722, Republic of Korea
| | - Seongjae Jo
- Infectious
Disease Research Center, Korea Research
Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea
| | - Kyung Ho Kim
- Infectious
Disease Research Center, Korea Research
Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea
| | - Lina Kim
- Infectious
Disease Research Center, Korea Research
Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea
| | - Oh Seok Kwon
- Infectious
Disease Research Center, Korea Research
Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea
- Department
of Biotechnology, University of Science
& Technology (UST), Daejeon 34141, Republic of Korea
- College
of Biotechnology and Bioengineering, Sungkyunkwan
University, Suwon 16419, Republic of Korea
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18
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László S, Hajna Z, Egyed A, Pintér E, Wagner Ö. Development of a Silicone-Based Polymer Matrix as a Suitable Transdermal Therapeutic System for Diallyl Disulfide. Pharmaceuticals (Basel) 2022; 15:ph15101182. [PMID: 36297294 PMCID: PMC9612217 DOI: 10.3390/ph15101182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/14/2022] [Accepted: 09/16/2022] [Indexed: 11/16/2022] Open
Abstract
There is an unmet need for novel therapeutic tools relieving chronic pain. Hydrogen sulfide (H2S) is highly involved in pain processes; however, the development of ideal matrices for sulfide donor compounds remains a great pharmaceutical challenge. We aimed to establish a suitable transdermal therapeutic system (TTS) using the H2S donor diallyl disulfide (DADS) as a model compound. After the preparation of DADS, its solubility was investigated in different liquid excipients (propylene glycol, polyethylene glycol, silicone oil) and its membrane diffusivity was assessed in silicone matrices of different compositions. Drug-releasing properties of DADS-containing patches with different silicone oil contents were determined with Franz and flow-through cells. We found a correlation between the liquid excipient content of the patch and the diffusion rate of DADS. DADS showed the best solubility in dimethyl silicone oil, and the diffusion constant was proportional to the amount of oil above the 3 m/m% threshold value. The 8-day-old patch showed a significantly lower, but better-regulated, drug release over time than the 4-day-old one. In conclusion, the silicone-based polymer matrix developed in this study is suitable for stable storage and optimal release of DADS, providing a good basis for a TTS applied in chronic pain.
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Affiliation(s)
- Szabolcs László
- Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti u. 12., H-7624 Pécs, Hungary
- Department of Inorganic and Analytical Chemistry, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary
| | - Zsófia Hajna
- Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti u. 12., H-7624 Pécs, Hungary
- Molecular Pharmacology Research Group, Szentágothai Research Centre, University of Pécs, Ifjúság ú. 20., H-7624 Pécs, Hungary
- Correspondence: ; Tel.: +36-72-538-212
| | - Attila Egyed
- Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Magyar Tudósok Körútja 2., H-1117 Budapest, Hungary
| | - Erika Pintér
- Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti u. 12., H-7624 Pécs, Hungary
- Molecular Pharmacology Research Group, Szentágothai Research Centre, University of Pécs, Ifjúság ú. 20., H-7624 Pécs, Hungary
| | - Ödön Wagner
- Department of Inorganic and Analytical Chemistry, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary
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Catalfamo LM, Marrone G, Basilicata M, Vivarini I, Paolino V, Della-Morte D, De Ponte FS, Di Daniele F, Quattrone D, De Rinaldis D, Bollero P, Di Daniele N, Noce A. The Utility of Capsicum annuum L. in Internal Medicine and In Dentistry: A Comprehensive Review. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:11187. [PMID: 36141454 PMCID: PMC9517535 DOI: 10.3390/ijerph191811187] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 09/01/2022] [Accepted: 09/03/2022] [Indexed: 06/16/2023]
Abstract
Capsaicin is a chili peppers extract, genus Capsicum, commonly used as a food spice. Since ancient times, Capsaicin has been used as a "homeopathic remedy" for treating a wild range of pathological conditions but without any scientific knowledge about its action. Several studies have demonstrated its potentiality in cardiovascular, nephrological, nutritional, and other medical fields. Capsaicin exerts its actions thanks to the bond with transient receptor potential vanilloid subtype 1 (TRPV1). TRPV1 is a nociceptive receptor, and its activation starts with a neurosensitive impulse, responsible for a burning pain sensation. However, constant local application of Capsaicin desensitized neuronal cells and leads to relief from neuropathic pain. In this review, we analyze the potential adjuvant role of Capsaicin in the treatment of different pathological conditions either in internal medicine or dentistry. Moreover, we present our experience in five patients affected by oro-facial pain consequent to post-traumatic trigeminal neuropathy, not responsive to any remedy, and successfully treated with topical application of Capsaicin. The topical application of Capsaicin is safe, effective, and quite tolerated by patients. For these reasons, in addition to the already-proven beneficial actions in the internal field, it represents a promising method for the treatment of neuropathic oral diseases.
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Affiliation(s)
- Luciano Maria Catalfamo
- Department of Biomedical and Dental Sciences, Morphological and Functional Images, University Hospital of Messina, 98100 Messina, Italy
| | - Giulia Marrone
- UOC of Internal Medicine-Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Michele Basilicata
- UOSD Special Care Dentistry, Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00100 Rome, Italy
| | - Ilaria Vivarini
- UOC of Internal Medicine-Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Vincenza Paolino
- UOSD Special Care Dentistry, Department of Systems Medicine, University of Rome Tor Vergata, 00100 Rome, Italy
| | - David Della-Morte
- Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
- Department of Human Sciences and Quality of Life Promotion, San Raffaele University, 00166 Rome, Italy
- Department of Neurology, Evelyn F. McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
| | - Francesco Saverio De Ponte
- Department of Biomedical and Dental Sciences, Morphological and Functional Images, University Hospital of Messina, 98100 Messina, Italy
| | - Francesca Di Daniele
- School of Applied Medical, Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
- UOSD of Dermatology, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Domenico Quattrone
- Department of Biomedical and Dental Sciences, Morphological and Functional Images, University Hospital of Messina, 98100 Messina, Italy
| | - Danilo De Rinaldis
- Department of Biomedical and Dental Sciences, Morphological and Functional Images, University Hospital of Messina, 98100 Messina, Italy
| | - Patrizio Bollero
- UOSD Special Care Dentistry, Department of Systems Medicine, University of Rome Tor Vergata, 00100 Rome, Italy
| | - Nicola Di Daniele
- UOC of Internal Medicine-Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Annalisa Noce
- UOC of Internal Medicine-Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
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Kuderer S, Vagedes K, Szöke H, Kohl M, Joos S, Gündling PW, Vagedes J. Do ginger footbaths improve symptoms of insomnia more than footbaths with warm water only? - A randomized controlled study. Complement Ther Med 2022; 67:102834. [PMID: 35439548 DOI: 10.1016/j.ctim.2022.102834] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 04/13/2022] [Accepted: 04/15/2022] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVES To compare the effects between warm water (WW) and ginger footbaths (WW+ginger) on sleep quality and warmth regulation in adults with self-reported insomnia symptoms. METHODS A prospective randomized-controlled study in which 28 participants (mean age 50.9 years, 64.3% women, insomnia symptom duration 11.4 years) were randomized to receive WW (n = 13) or WW+ginger (n = 15) daily for 2 weeks. Treatment involved nightly footbaths (12 liters of 38-42 °C warm tap water, maximum duration 20 min) with and without topical ginger (80 g of powdered ginger rhizomes). MAIN OUTCOME MEASURES The primary outcome measure was self-reported sleep quality (global score from Pittsburgh Sleep Quality Index, PSQI) at 2 weeks. Secondary outcomes included measures of insomnia severity (Insomnia Severity Index, ISI) and warmth regulation (Herdecke Warmth Perception Questionnaire, HWPQ and 24-hour distal-proximal skin temperature gradient, DPG). RESULTS WW+ginger had no greater effect on PSQI (mean between-difference 0.0 [95% CI -3.0 to 2.9], Cohen's d=0.0) or ISI (-0.2 [-3.9 to 3.4], 0.0) than WW. Nor were there any significant differences in HWPQ perceived warmth (0.1 ≥d≥0.5) or DPG (0.1 ≥d≥0.4) between WW and WW+ginger. Both groups improved over time in PSQI (WW+ginger: d=0.7, WW: d=1.3) and ISI (WW+ginger: d=0.8, WW: d=1.0). Perceived warmth of the feet increased only in WW+ginger over time (d=0.6, WW: d=0.0). CONCLUSIONS This dose of ginger (6.67 g/liter) did not have greater effects on sleep quality, insomnia severity or warmth regulation than WW. Considering effect sizes, costs and risks, the use of WW would be recommended over WW+ginger in this patient population.
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Affiliation(s)
- Silja Kuderer
- Research Department, ARCIM Institute (Academic Research in Complementary and Integrative Medicine), Im Haberschlai 7, 70794 Filderstadt, Germany
| | - Katrin Vagedes
- Research Department, ARCIM Institute (Academic Research in Complementary and Integrative Medicine), Im Haberschlai 7, 70794 Filderstadt, Germany
| | - Henrik Szöke
- Department of Integrative Medicine, University of Pécs, Vörösmarty utca 3, 7623 Pécs, Hungary
| | - Matthias Kohl
- Institute of Precision Medicine, University Furtwangen, Jakob-Kienzle-Straße 17, 78054 VS-Schwenningen, Germany
| | - Stefanie Joos
- Institute for General Practice and Interprofessional Care, University Hospital Tübingen, Osianderstraße 5, 72076 Tübingen, Germany
| | - Peter W Gündling
- Hochschule Fresenius, University of Applied Sciences, Limburger Str. 2, 65510 Idstein, Germany
| | - Jan Vagedes
- Research Department, ARCIM Institute (Academic Research in Complementary and Integrative Medicine), Im Haberschlai 7, 70794 Filderstadt, Germany; Department of Neonatology, University Hospital Tübingen, Calwerstraße 7, 72076 Tübingen, Germany; Department of Pediatrics, Filderklinik, Im Haberschlai 7, 70794 Filderstadt, Germany.
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21
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D'Souza RS, Barman R, Joseph A, Abd-Elsayed A. Evidence-Based Treatment of Painful Diabetic Neuropathy: a Systematic Review. Curr Pain Headache Rep 2022; 26:583-594. [PMID: 35716275 DOI: 10.1007/s11916-022-01061-7] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/26/2022] [Indexed: 12/25/2022]
Abstract
PURPOSE OF REVIEW Painful diabetic neuropathy (PDN) manifests with pain typically in the distal lower extremities and can be challenging to treat. The authors appraised the literature for evidence on conservative, pharmacological, and neuromodulation treatment options for PDN. RECENT FINDINGS Intensive glycemic control with insulin in patients with type 1 diabetes may be associated with lower odds of distal symmetric polyneuropathy compared to patients who receive conventional insulin therapy. First-line pharmacologic therapy for PDN includes gabapentinoids (pregabalin and gabapentin) and duloxetine. Additional pharmacologic modalities that are approved by the Food and Drug Administration (FDA) but are considered second-line agents include tapentadol and 8% capsaicin patch, although studies have revealed modest treatment effects from these modalities. There is level I evidence on the use of dorsal column spinal cord stimulation (SCS) for treatment of PDN, delivering either a 10-kHz waveform or tonic waveform. In summary, this review provides an overview of treatment options for PDN. Furthermore, it provides updates on the level of evidence for SCS therapy in cases of PDN refractory to conventional medical therapy.
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Affiliation(s)
- Ryan S D'Souza
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
| | - Ross Barman
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
| | - Amira Joseph
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
| | - Alaa Abd-Elsayed
- Department of Anesthesiology and Perioperative Medicine, University of Wisconsin, Madison, WI, USA.
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22
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Cheng AY, Wong LS. Uremic Pruritus: From Diagnosis to Treatment. Diagnostics (Basel) 2022; 12:diagnostics12051108. [PMID: 35626264 PMCID: PMC9140050 DOI: 10.3390/diagnostics12051108] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/22/2022] [Accepted: 04/26/2022] [Indexed: 12/15/2022] Open
Abstract
Uremic pruritus, or chronic kidney disease-associated pruritus, is common, bothersome, and sometimes debilitating in patients with chronic kidney disease or end-stage renal disease. Due to its variable clinical manifestations, the diagnosis of uremic pruritus requires exquisite evaluation. Excluding itch resulting from other dermatological causes as well as other systemic conditions is essential for a proper diagnosis. The pathophysiology of uremic pruritus remains uncertain. Hypotheses including toxin deposition, immune system dysregulation, peripheral neuropathy, and opioid imbalance are supposed. This review summarizes the way to accurately diagnose uremic pruritus and describes the latest treatment options.
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Affiliation(s)
| | - Lai-San Wong
- Correspondence: ; Tel.: +886-7-731-7123 (ext. 2299)
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23
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D'Souza RS, Langford B, Dombovy-Johnson M, Abd-Elsayed A. Neuromodulation Interventions for the Treatment of Painful Diabetic Neuropathy: a Systematic Review. Curr Pain Headache Rep 2022; 26:365-377. [PMID: 35226258 DOI: 10.1007/s11916-022-01035-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/30/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Painful diabetic neuropathy (PDN) is a prevalent and debilitating condition, characterized by severe burning, tingling, and lancinating pain usually located in the distal lower extremities. In addition to manifesting with severe pain, PDN may also be associated with poor quality of life and sleep, mood disorders, burns, falls, and social withdrawal. The authors appraised the current body of literature for evidence on neuromodulation interventions for PDN. RECENT FINDINGS In patients with refractory PDN unresponsive to conventional medical management (glucose optimization and oral analgesic medications), there is level I evidence supporting the use of 10-kHz and tonic dorsal column spinal cord stimulation (SCS). Included studies reported significant associations between 10-kHz and tonic dorsal column SCS and superior analgesic outcomes, physical functioning, and patient satisfaction. Current level of evidence remains limited for other modalities of neuromodulation for PDN including burst SCS (level II-3), dorsal root ganglion SCS (level III), and peripheral nerve stimulation (level II-3). Some studies reported improvements in neurological physical examination, sensory testing, and/or reflex testing in patients undergoing 10-kHz SCS for treatment of PDN. In summary, the purpose of this review is to equip provider with important updates on the use of neuromodulation interventions for the treatment of PDN that is refractory to conventional medical therapy, with current level I evidence supporting use of 10-kHz and tonic SCS for PDN.
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Affiliation(s)
- Ryan S D'Souza
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
| | - Brendan Langford
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
| | | | - Alaa Abd-Elsayed
- Department of Anesthesiology and Perioperative Medicine, University of Wisconsin, Madison, WI, USA.
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24
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Wang X, Bao C, Li Z, Yue L, Hu L. Side Effects of Opioids Are Ameliorated by Regulating TRPV1 Receptors. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19042387. [PMID: 35206575 PMCID: PMC8872563 DOI: 10.3390/ijerph19042387] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/06/2022] [Accepted: 02/09/2022] [Indexed: 11/23/2022]
Abstract
Humans have used opioids to suppress moderate to severe pain for thousands of years. However, the long-term use of opioids has several adverse effects, such as opioid tolerance, opioid-induced hyperalgesia, and addiction. In addition, the low efficiency of opioids in controlling neuropathic pain limits their clinical applications. Combining nonopioid analgesics with opioids to target multiple sites along the nociceptive pathway may alleviate the side effects of opioids. This study reviews the feasibility of reducing opioid side effects by regulating the transient receptor potential vanilloid 1 (TRPV1) receptors and summarizes the possible underlying mechanisms. Blocking and activating TRPV1 receptors can improve the therapeutic profile of opioids in different manners. TRPV1 and μ-opioid receptors are bidirectionally regulated by β-arrestin2. Thus, drug combinations or developing dual-acting drugs simultaneously targeting μ-opioid and TRPV1 receptors may mitigate opioid tolerance and opioid-induced hyperalgesia. In addition, TRPV1 receptors, especially expressed in the dorsal striatum and nucleus accumbens, participate in mediating opioid reward, and its regulation can reduce the risk of opioid-induced addiction. Finally, co-administration of TRPV1 antagonists and opioids in the primary action sites of the periphery can significantly relieve neuropathic pain. In general, the regulation of TRPV1 may potentially ameliorate the side effects of opioids and enhance their analgesic efficacy in neuropathic pain.
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Affiliation(s)
- Xiaqing Wang
- CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, China; (X.W.); (C.B.); (Z.L.)
- Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Chongyu Bao
- CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, China; (X.W.); (C.B.); (Z.L.)
- Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Zhenjiang Li
- CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, China; (X.W.); (C.B.); (Z.L.)
- Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Lupeng Yue
- CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, China; (X.W.); (C.B.); (Z.L.)
- Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China
- Correspondence: (L.Y.); (L.H.)
| | - Li Hu
- CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, China; (X.W.); (C.B.); (Z.L.)
- Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China
- Correspondence: (L.Y.); (L.H.)
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25
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Leavell Y, Simpson DM. The role of the capsaicin 8% patch in the treatment of painful diabetic peripheral neuropathy. Pain Manag 2022; 12:595-609. [PMID: 35152709 DOI: 10.2217/pmt-2021-0025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Treatment of painful diabetic peripheral neuropathy (PDPN) is challenging and often limited by drug tolerability and adverse effects. This review article focuses on the high-dose (8%) capsaicin patch that allows for improved efficacy and reduced application frequency in comparison to low-dose capsaicin formulations. Systemic absorption is minimal resulting in fewer systemic side effects than first-line oral medications. There is evidence that capsaicin patch treatment is well-tolerated, safe and provides effective pain relief maintained for several weeks; well-powered studies are needed to confirm these findings. The capsaicin 8% patch may benefit patients at high risk for adverse effects from oral medication, polypharmacy or inadequate pain relief from first-line therapies.
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Affiliation(s)
- Yaowaree Leavell
- Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA
| | - David M Simpson
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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26
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Abstract
Managing chronic pain remains a major unmet clinical challenge. Patients can be treated with a range of interventions, but pharmacotherapy is the most common. These include opioids, antidepressants, calcium channel modulators, sodium channel blockers, and nonsteroidal anti-inflammatory drugs. Many of these drugs target a particular mechanism; however, chronic pain in many diseases is multifactorial and induces plasticity throughout the sensory neuroaxis. Furthermore, comorbidities such as depression, anxiety, and sleep disturbances worsen quality of life. Given the complexity of mechanisms and symptoms in patients, it is unsurprising that many fail to achieve adequate pain relief from a single agent. The efforts to develop novel drug classes with better efficacy have not always proved successful; a multimodal or combination approach to analgesia is an important strategy in pain control. Many patients frequently take more than one medication, but high-quality evidence to support various combinations is often sparse. Ideally, combining drugs would produce synergistic action to maximize analgesia and reduce side effects, although sub-additive and additive analgesia is still advantageous if additive side-effects can be avoided. In this review, we discuss pain mechanisms, drug actions, and the rationale for mechanism-led treatment selection.Abbreviations: COX - cyclooxygenase, CGRP - calcitonin gene-related peptide, CPM - conditioned pain modulation, NGF - nerve growth factor, NNT - number needed to treat, NMDA - N-methyl-d-aspartate, NSAID - nonsteroidal anti-inflammatory drugs, TCA - tricyclic antidepressant, SNRI - serotonin-noradrenaline reuptake inhibitor, QST - quantitative sensory testing.
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Affiliation(s)
- Ryan Patel
- Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, UK
| | - Anthony H Dickenson
- Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, UK
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27
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Chen H, Li N, Zhan X, Zheng T, Huang X, Chen Q, Song Z, Yang F, Nie H, Zhang Y, Zheng B, Gong Q. Capsaicin Protects Against Lipopolysaccharide-Induced Acute Lung Injury Through the HMGB1/NF-κB and PI3K/AKT/mTOR Pathways. J Inflamm Res 2021; 14:5291-5304. [PMID: 34703269 PMCID: PMC8524366 DOI: 10.2147/jir.s309457] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 09/27/2021] [Indexed: 11/23/2022] Open
Abstract
Purpose Capsaicin (8-methyl-N-geranyl-6-nonamide; CAP) is an alkaloid isolated from chili peppers, which has complex pharmacological properties, including beneficial effects against various diseases. The aim of this study was to investigate the role of CAP in lipopolysaccharide (LPS)-induced acute lung injury (ALI), and the possible underlying mechanisms. Materials and Methods ALI was induced by intranasal administration of LPS (0.5 mg/kg), and CAP (1 mg/kg) injected intraperitoneally 3 days before exposure to LPS. Then, the histopathological changes were evaluated by hematoxylin and eosin staining. Enzyme-linked immunosorbent assay and qPCR were used to detect pro-inflammatory cytokines in serum and lung tissue. The expressions of HMGB1/NF-κB, PI3K/AKT/mTOR signaling pathways and apoptosis-associated molecules were determined by Western blot and/or qPCR. In addition, the lung cell apoptosis was analyzed by TUNEL staining, and the expression and location of cleaved caspase-3 were detected by immunofluorescence analysis. Results CAP pretreatment significantly protected mice from LPS-induced ALI, with reduced lung wet/dry weight ratio, lung histological damage, myeloperoxidase (MPO) activity, malondialdehyde (MDA) content and pro-inflammatory cytokine levels, and significant increased superoxide dismutase (SOD) activity. In addition, CAP pretreatment significantly inhibited the high-mobility group protein B1 (HMGB1) expression, nuclear factor-kappa B (NF-κB) activation, and the PI3K/AKT/mTOR signaling pathway. Furthermore, mice pre-treated with CAP exhibited reduced apoptosis of lung tissues, with associated down-regulation of caspase-3, cleaved caspase-3, and BAX expression, and up-regulation of BCL-2. Conclusion Our data demonstrate that CAP can protect against LPS-induced ALI by inhibiting oxidative stress, inflammatory responses and apoptosis through down-regulation of the HMGB1/NF-κB and PI3K/AKT/mTOR pathways.
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Affiliation(s)
- Hui Chen
- Department of Immunology, School of Medicine, Yangtze University, Jingzhou, People's Republic of China
| | - Na Li
- Department of Immunology, School of Medicine, Yangtze University, Jingzhou, People's Republic of China.,Department of Oncology, First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, People's Republic of China
| | - Xiang Zhan
- Department of Immunology, School of Medicine, Yangtze University, Jingzhou, People's Republic of China
| | - Ting Zheng
- Department of Immunology, School of Medicine, Yangtze University, Jingzhou, People's Republic of China
| | - Xinzhou Huang
- Department of Immunology, School of Medicine, Yangtze University, Jingzhou, People's Republic of China
| | - Qianglin Chen
- Department of Immunology, School of Medicine, Yangtze University, Jingzhou, People's Republic of China
| | - Zihao Song
- Department of Immunology, School of Medicine, Yangtze University, Jingzhou, People's Republic of China
| | - Fei Yang
- Department of Immunology, School of Medicine, Yangtze University, Jingzhou, People's Republic of China.,Clinical Molecular Immunology Center, School of Medicine, Yangtze University, Jingzhou, People's Republic of China
| | - Hao Nie
- Department of Immunology, School of Medicine, Yangtze University, Jingzhou, People's Republic of China.,Clinical Molecular Immunology Center, School of Medicine, Yangtze University, Jingzhou, People's Republic of China
| | - Yanxiang Zhang
- Clinical Molecular Immunology Center, School of Medicine, Yangtze University, Jingzhou, People's Republic of China
| | - Bing Zheng
- Department of Immunology, School of Medicine, Yangtze University, Jingzhou, People's Republic of China.,Clinical Molecular Immunology Center, School of Medicine, Yangtze University, Jingzhou, People's Republic of China
| | - Quan Gong
- Department of Immunology, School of Medicine, Yangtze University, Jingzhou, People's Republic of China.,Clinical Molecular Immunology Center, School of Medicine, Yangtze University, Jingzhou, People's Republic of China
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28
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Kondo H, Kondo M, Hayashi K, Kusafuka S, Hamamura K, Tanaka K, Kodama D, Hirai T, Sato T, Ariji Y, Miyazawa K, Ariji E, Goto S, Togari A. Orthodontic tooth movement-activated sensory neurons contribute to enhancing osteoclast activity and tooth movement through sympathetic nervous signalling. Eur J Orthod 2021; 44:404-411. [PMID: 34642757 DOI: 10.1093/ejo/cjab072] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Orthodontic tooth movement (OTM) increases sympathetic and sensory neurological markers in periodontal tissue. However, the relationship between the sympathetic and sensory nervous systems during OTM remains unclear. Therefore, the present study investigated the relationship between the sympathetic and sensory nervous systems activated by OTM using pharmacological methods. MATERIALS AND METHODS We compared the effects of sympathectomy and sensory nerve injury during OTM in C57BL6/J mice. Capsaicin (CAP) was used to induce sensory nerve injury. Sympathectomy was performed using 6-hydroxydopamine. To investigate the effects of a β-agonist on sensory nerve injury, isoproterenol (ISO) was administered to CAP-treated mice. Furthermore, to examine the role of the central nervous system in OTM, the ventromedial hypothalamic nucleus (VMH) was ablated using gold thioglucose. RESULTS Sensory nerve injury and sympathectomy both suppressed OTM and decreased the percent of the alveolar socket covered with osteoclasts (Oc.S/AS) in periodontal tissue. Sensory nerve injury inhibited increases in OTM-induced calcitonin gene-related peptide (CGRP) immunoreactivity (IR), a marker of sensory neurons, and tyrosine hydroxylase (TH) IR, a marker of sympathetic neurons, in periodontal tissue. Although sympathectomy did not decrease the number of CGRP-IR neurons in periodontal tissue, OTM-induced increases in the number of TH-IR neurons were suppressed. The ISO treatment restored sensory nerve injury-inhibited tooth movement and Oc.S/AS. Furthermore, the ablation of VMH, the centre of the sympathetic nervous system, suppressed OTM-induced increases in tooth movement and Oc.S/AS. CONCLUSIONS The present results suggest that OTM-activated sensory neurons contribute to enhancements in osteoclast activity and tooth movement through sympathetic nervous signalling.
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Affiliation(s)
- Hisataka Kondo
- Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Mayo Kondo
- Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.,Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Kaori Hayashi
- Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.,Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Sae Kusafuka
- Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.,Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Kazunori Hamamura
- Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Kenjiro Tanaka
- Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Daisuke Kodama
- Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Takao Hirai
- Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Takuma Sato
- Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Yoshiko Ariji
- Department of Oral and Maxillofacial Radiology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Ken Miyazawa
- Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Eiichiro Ariji
- Department of Oral and Maxillofacial Radiology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Shigemi Goto
- Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Akifumi Togari
- Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
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29
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Casale R. Capsaicin 179-mg cutaneous patch in the treatment of post-surgical neuropathic pain: a scoping review of current evidence and place in therapy. Expert Rev Neurother 2021; 21:1147-1158. [PMID: 34461799 DOI: 10.1080/14737175.2021.1974842] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 08/27/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The use of topical agents has been suggested for post-surgical neuropathic pain. A high-concentration capsaicin 179-mg cutaneous patch (Qutenza™) is licensed in adults for chronic neuropathic pain in the EU, and neuropathic pain with post-herpetic neuralgia and neuropathic pain with diabetic peripheral neuropathy in the USA. This article aims to describe the use of a topical capsaicin 179-mg cutaneous patch in the treatment of PSNP. AREA COVERED This narrative review presents the relevant clinical aspects of the use of a topical capsaicin 179-mg cutaneous patch for the treatment of post-surgical neuropathic pain (PSNP). Randomized control trials, observational studies, case series, and reports investigating the clinical use of the capsaicin patch were searched through MEDLINE, EMBASE, AMED, Cochrane Library, CINAHL, Web of Science, and ROAD databases. Trials from citation lists of reviewed articles and hand-searching were added. The search concluded in September 2020. 10/20 articles were considered. EXPERT OPINION Some clinical studies demonstrated the efficacy of the capsaicin 179-mg patch in PSNP as monotherapy and concomitant treatment with oral treatments. This topical treatment of PSNP is better tolerated and accepted compared with systemic treatments. To maximize the effectiveness of the treatment, correct administration recommendations should be followed.
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Affiliation(s)
- Roberto Casale
- Opusmedica Persons, Care & Research - PC&R, Piacenza, Italy
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30
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Sheehan GD, Martin MK, Young VA, Powell R, Bhattacharjee A. Thermal hyperalgesia and dynamic weight bearing share similar recovery dynamics in a sciatic nerve entrapment injury model. NEUROBIOLOGY OF PAIN 2021; 10:100079. [PMID: 34917858 PMCID: PMC8665403 DOI: 10.1016/j.ynpai.2021.100079] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/01/2021] [Accepted: 12/01/2021] [Indexed: 11/28/2022]
Abstract
The sciatic nerve cuff model of neuropathic pain exhibits pain recovery. Thermal hyperalgesia and dynamic weight bearing display similar pain recovery profiles, whereas mechanical allodynia persists. Dynamic weight bearing is a non-reflexive, pain assessment of ongoing pain during nerve entrapment. Chronic constriction injuries (CCI) of the sciatic nerve are widely used nerve entrapment animal models of neuropathic pain. Two common pain behaviors observed following CCI are thermal hyperalgesia and mechanical allodynia, measured by the Hargreaves and von Frey tests, respectively. While thermal hyperalgesia tends to recover by 30 days, mechanical allodynia can persist for many more months thereafter. Consequently, mechanical allodynia has been used extensively as a measure of ‘chronic pain’ focusing on the circuitry changes that occur within the spinal cord. Here, using the sciatic nerve cuff variant of CCI in mice, we propose that in contrast to these evoked measures of nociceptive hypersensitivity, dynamic weight bearing provides a more clinically relevant behavioral measure for ongoing pain during nerve injury. We found that the effect of sciatic nerve cuff on the ratio of weight bearing by the injured relative to uninjured hindlimbs more closely resembled that of thermal hyperalgesia, following a trend toward recovery by 30 days. We also found an increase in the percent of body weight bearing by the contralateral paw that is not seen in the previously tested behaviors. These results demonstrate that dynamic weight bearing is a reliable measure of non-evoked neuropathic pain and suggest that thermal hyperalgesia, rather than mechanical allodynia, provides a proxy measure for nerve entrapment-induced ongoing pain.
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Affiliation(s)
- Garrett D. Sheehan
- Program in Neuroscience, University at Buffalo, The State University of New York, Buffalo, NY 14203, USA
| | - Molly K. Martin
- Program in Neuroscience, University at Buffalo, The State University of New York, Buffalo, NY 14203, USA
| | - Violet A. Young
- Program in Neuroscience, University at Buffalo, The State University of New York, Buffalo, NY 14203, USA
| | - Rasheen Powell
- Department of Pharmacology and Toxicology, University at Buffalo, The State University of New York, Buffalo, NY 14203, USA
| | - Arin Bhattacharjee
- Program in Neuroscience, University at Buffalo, The State University of New York, Buffalo, NY 14203, USA
- Department of Pharmacology and Toxicology, University at Buffalo, The State University of New York, Buffalo, NY 14203, USA
- Corresponding author at: Department of Pharmacology and Toxicology, University at Buffalo, The State University of New York USA.
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31
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Shibata M, Kayama Y, Takizawa T, Ibata K, Shimizu T, Yuzaki M, Suzuki N, Nakahara J. Resilience to capsaicin-induced mitochondrial damage in trigeminal ganglion neurons. Mol Pain 2021; 16:1744806920960856. [PMID: 32985330 PMCID: PMC7536481 DOI: 10.1177/1744806920960856] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Capsaicin is an agonist of transient receptor potential cation channel subfamily V member 1 (TRPV1). Strong TRPV1 stimulation with capsaicin causes mitochondrial damage in primary sensory neurons. However, the effect of repetitive and moderate exposure to capsaicin on the integrity of neuronal mitochondria remains largely unknown. Our electron microscopic analysis revealed that repetitive stimulation of the facial skin of mice with 10 mM capsaicin induced short-term damage to the mitochondria in small-sized trigeminal ganglion neurons. Further, capsaicin-treated mice exhibited decreased sensitivity to noxious heat stimulation, indicating TRPV1 dysfunction, in parallel with the mitochondrial damage in the trigeminal ganglion neurons. To analyze the capsaicin-induced mitochondrial damage and its relevant cellular events in detail, we performed cell-based assays using TRPV1-expressing PC12 cells. Dose-dependent capsaicin-mediated mitochondrial toxicity was observed. High doses of capsaicin caused rapid destruction of mitochondrial internal structure, while low doses induced mitochondrial swelling. Further, capsaicin induced a dose-dependent loss of mitochondria and autophagy-mediated degradation of mitochondria (mitophagy). Concomitantly, transcriptional upregulation of mitochondrial proteins, cytochrome c oxidase subunit IV, Mic60/Mitofilin, and voltage-dependent anion channel 1 was observed, which implied induction of mitochondrial biogenesis to compensate for the loss of mitochondria. Collectively, although trigeminal ganglion neurons transiently exhibit mitochondrial damage and TRPV1 dysfunction following moderate capsaicin exposure, they appear to be resilient to such a challenge. Our in vitro data show a dose-response relationship in capsaicin-mediated mitochondrial toxicity. We postulate that induction of mitophagy and mitochondrial biogenesis in response to capsaicin stimulation play important roles in repairing the damaged mitochondrial system.
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Affiliation(s)
- Mamoru Shibata
- Department of Neurology, Keio University School of Medicine, Japan
| | - Yohei Kayama
- Department of Neurology, Keio University School of Medicine, Japan
| | - Tsubasa Takizawa
- Department of Neurology, Keio University School of Medicine, Japan
| | - Keiji Ibata
- Department of Physiology, Keio University School of Medicine, Japan.,Department of Physiology, St. Marianna Medical University, Japan
| | | | - Michisuke Yuzaki
- Department of Physiology, Keio University School of Medicine, Japan
| | - Norihiro Suzuki
- Department of Neurology, Keio University School of Medicine, Japan
| | - Jin Nakahara
- Department of Neurology, Keio University School of Medicine, Japan
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Etienne R, Laurent M, Henry A, Bioy A, Salleron J, Schohn CH, Cretineau N. Interest of a standardized hypnotic message for the reduction of pain and anxiety in cancer patients treated by capsaicin patch for neuropathic pain: a randomized controlled trial. BMC Complement Med Ther 2021; 21:154. [PMID: 34044838 PMCID: PMC8161949 DOI: 10.1186/s12906-021-03329-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 05/17/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Neuropathic pain is characterized by spontaneous painful symptoms. Medical therapies include the use of a capsaicin 8% patch (Qutenza®, Grünenthal Gmbh, Germany), and patients may experience a sharp burning sensation at application and removal of the patch. This study aimed to evaluate the impact of playing a standardized hypnosis recording during application, on the pain and anxiety induced by capsaicin treatment. METHODS In a randomized, controlled trial, we assessed the benefits of the intervention firstly on pain and secondly on anxiety, as measured using numerical rating scales. All patients had application of the capsaicin patch, including the possibility for the patient to apply a cold patch. Participants were randomly assigned to one of 3 groups, namely the "Standard group" (no intervention), "Hypnosis group", in which a standardized hypnotic message was played during application, or the "Music group" in which relaxing music was played during application of the patch. RESULTS Sixty-nine patients were included. Overall, there was no significant difference in pain scores between groups (p = 0.355). Compared to standard application, anxiety was significantly lower in the hypnosis group after application (p = 0.007), with no significant difference between the standard and music arms (p = 0.271), or between the hypnosis and music arms (p = 0.423). CONCLUSIONS Listening to a standardized hypnotic message during application of a capsaicin patch was found to significantly lower anxiety. These findings indicate that the use of a hypnotic message can reduce discomfort and warrant its evaluation in other indications of pain or anxiety during treatment procedures. TRIAL REGISTRATION NCT02822625 .
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Affiliation(s)
- Rémi Etienne
- Department of Supportive Care in Oncology, Institut de Cancérologie de Lorraine, Université de Lorraine, F-54519, Vandœuvre-lès-Nancy, France
| | - Myriam Laurent
- Department of Supportive Care in Oncology, Institut de Cancérologie de Lorraine, Université de Lorraine, F-54519, Vandœuvre-lès-Nancy, France
| | - Aline Henry
- Department of Supportive Care in Oncology, Institut de Cancérologie de Lorraine, Université de Lorraine, F-54519, Vandœuvre-lès-Nancy, France
| | - Antoine Bioy
- University of Paris 8, Laboratory of Psychopathology and Neuropsychology, St Denis, Paris, France
| | - Julia Salleron
- Departement of biostatistics, Institut de Cancérologie de Lorraine, Université de Lorraine, F-54519, Vandœuvre-lès-Nancy, France.
| | - Cécile Huin Schohn
- Research Department, Institut de Cancérologie de Lorraine, Université de Lorraine, F-54519, Vandœuvre-lès-Nancy, France
| | - Nathalie Cretineau
- Department of Supportive Care in Oncology, Institut de Cancérologie de Lorraine, Université de Lorraine, F-54519, Vandœuvre-lès-Nancy, France
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33
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Anido J, Rojo E, Funcia I, Becerra A, Bravo E, Acedo G. Use of capsaicin for the treatment of localized neuropathic pain post-thoracotomy. Minerva Anestesiol 2021; 87:1272-1273. [PMID: 34036773 DOI: 10.23736/s0375-9393.21.15804-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- José Anido
- Department of Anesthesiology and Reanimation, University Hospital of Badajoz, Badajoz, Spain -
| | - Elena Rojo
- Unit Pain, La Princesa University Hospital, Madrid, Spain
| | - Iliana Funcia
- Department of Anesthesiology and Reanimation, University Hospital of Badajoz, Badajoz, Spain
| | - Alejandra Becerra
- Department of Anesthesiology and Reanimation, University Hospital of Badajoz, Badajoz, Spain
| | - Estella Bravo
- Unit Pain, Vivian Pellas Hospital, Managua, Nicaragua
| | - Guadalupe Acedo
- Department of Anesthesiology and Reanimation, University Hospital of Badajoz, Badajoz, Spain
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Sultana A, Singla RK, He X, Sun Y, Alam MS, Shen B. Topical Capsaicin for the Treatment of Neuropathic Pain. Curr Drug Metab 2021; 22:198-207. [PMID: 33198614 DOI: 10.2174/1389200221999201116143701] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 08/05/2020] [Accepted: 08/09/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Neuropathic pain (NP) is an egregious problem worldwide. Due to the side-effects of oral drugs, drugs delivered directly to the affected area of pain are preferred. OBJECTIVE Capsaicin, a chemical compound isolated from chili peppers, is used as an analgesic in topical ointments and dermal patches to alleviate pain. Objective of the study is to review the application and functionality of topical capsaicin in treatment of neuropathic pain. DATA SOURCES To systematically review capsaicin's functions on NP, we retrieved articles from the PubMed database published in the last ten years. STUDY ELIGIBILITY CRITERIA The inclusion criteria were capsaicin and the use of capsaicin for the treatment of NP; on the other hand, articles were excluded according to the mentioned criteria such as abstracts, articles written in any language other than English, incomplete articles, and conference papers. PARTICIPANTS AND INTERVENTIONS Out of 265 articles, 108 articles were selected after filtering through the inclusion and exclusion criteria. The data and knowledge currently existing for capsaicin treatment in NP are summarized. RESULTS This review indicates that capsaicin effectively improves NP treatment without affecting the motor and large nerve fibres involved in sensory function. Transient receptor potential channel vanilloid type 1 (TRPV1) is the capsaicin receptor expressed in central and peripheral terminals of a sensitive primary nerve cell. Conclusions and implications of key findings: Topical capsaicin has a sensible safety profile and is effective in reducing NP. Therefore, studies over the last decade suggest that capsaicin might be a potential drug for NP treatment.
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Affiliation(s)
- Adiba Sultana
- Center for Systems Biology, Soochow University, Suzhou, 215006, China
| | - Rajeev K Singla
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xuefei He
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Yan Sun
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Md Shahin Alam
- Center for Systems Biology, Soochow University, Suzhou, 215006, China
| | - Bairong Shen
- Center for Systems Biology, Soochow University, Suzhou, 215006, China
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Raja SN, Ringkamp M, Guan Y, Campbell JN. John J. Bonica Award Lecture: Peripheral neuronal hyperexcitability: the "low-hanging" target for safe therapeutic strategies in neuropathic pain. Pain 2021; 161 Suppl 1:S14-S26. [PMID: 33090736 DOI: 10.1097/j.pain.0000000000001838] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
| | - Matthias Ringkamp
- Neurological Surgery, Department of Neurosurgery, Johns Hopkins University, School of Medicine, Baltimore, MD, United States
| | - Yun Guan
- Departments of Anesthesiology and Critical Care Medicine and.,Neurological Surgery, Department of Neurosurgery, Johns Hopkins University, School of Medicine, Baltimore, MD, United States
| | - James N Campbell
- Neurological Surgery, Department of Neurosurgery, Johns Hopkins University, School of Medicine, Baltimore, MD, United States
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Ma K, Jiang W, Wang YX, Wang L, Lv Y, Liu JF, Liu RG, Liu H, Xiao LZ, Du DP, Lu LJ, Yang XQ, Xia LJ, Huang D, Fu ZJ, Peng BG, Liu YQ. Expert consensus of the Chinese Association for the Study of Pain on pain treatment with the transdermal patch. World J Clin Cases 2021; 9:2110-2122. [PMID: 33850930 PMCID: PMC8017498 DOI: 10.12998/wjcc.v9.i9.2110] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 02/14/2021] [Accepted: 03/09/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic pain lasting more than 3 mo, or even several years can lead to disability. Treating chronic pain safely and effectively is a critical challenge faced by clinicians. Because administration of analgesics through oral, intravenous or intramuscular routes is not satisfactory, research toward percutaneous delivery has gained interest. The transdermal patch is one such percutaneous delivery system that can deliver drugs through the skin and capillaries at a certain rate to achieve a systemic or local therapeutic effect in the affected area. It has many advantages including ease of administration and hepatic first pass metabolism avoidance as well as controlling drug delivery, which reduces the dose frequency and side effects. If not required, then the patch can be removed from the skin immediately. The scopolamine patch was the first transdermal patch to be approved for the treatment of motion sickness by the Food and Drug Administration in 1979. From then on, the transdermal patch has been widely used to treat many diseases. To date, no guidelines or consensus are available on the use of analgesic drugs through transdermal delivery. The pain branch of the Chinese Medical Association, after meeting and discussing with experts and based on clinical evidence, developed a consensus for promoting and regulating standard use of transdermal patches containing analgesic drugs.
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Affiliation(s)
- Ke Ma
- Department of Algology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Wei Jiang
- Department of Anesthesiology, Third Medical Center of People’s Liberation Army General Hospital, Beijing 100039, China
| | - Yun-Xia Wang
- Department of Algology, The Third People’s Hospital of Hubei Province, Hubei Zhongshan Hospital, Wuhan 430033, Hubei Province, China
| | - Lin Wang
- Department of Algology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China
| | - Yan Lv
- Department of Algology, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi Province, China
| | - Jin-Feng Liu
- Department of Algology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
| | - Rong-Guo Liu
- Department of Algology, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China
| | - Hui Liu
- Department of Algology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Li-Zu Xiao
- Department of Algology, Shenzhen Sixth People’s Hospital (Nanshan Hospital), Shenzhen 518000, Guangdong Province, China
| | - Dong-Ping Du
- Department of Algology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China
| | - Li-Juan Lu
- Department of Algology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Xiao-Qiu Yang
- Department of Algology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Ling-Jie Xia
- Department of Algology, Henan Provincial People’s Hospital, Zhengzhou 450000, Henan Province, China
| | - Dong Huang
- Department of Algology, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
| | - Zhi-Jian Fu
- Department of Algology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Bao-Gan Peng
- Department of Orthopedics, The Third Medical Center, General Hospital of the Chinese People’s Liberation Army, Beijing 100039, China
| | - Yan-Qing Liu
- Department of Algology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
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Transient Receptor Potential Vanilloid in the Brain Gliovascular Unit: Prospective Targets in Therapy. Pharmaceutics 2021; 13:pharmaceutics13030334. [PMID: 33806707 PMCID: PMC7999963 DOI: 10.3390/pharmaceutics13030334] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/20/2021] [Accepted: 02/22/2021] [Indexed: 12/25/2022] Open
Abstract
The gliovascular unit (GVU) is composed of the brain microvascular endothelial cells forming blood–brain barrier and the neighboring surrounding “mural” cells (e.g., pericytes) and astrocytes. Modulation of the GVU/BBB features could be observed in a variety of vascular, immunologic, neuro-psychiatric diseases, and cancers, which can disrupt the brain homeostasis. Ca2+ dynamics have been regarded as a major factor in determining BBB/GVU properties, and previous studies have demonstrated the role of transient receptor potential vanilloid (TRPV) channels in modulating Ca2+ and BBB/GVU properties. The physiological role of thermosensitive TRPV channels in the BBB/GVU, as well as their possible therapeutic potential as targets in treating brain diseases via preserving the BBB are reviewed. TRPV2 and TRPV4 are the most abundant isoforms in the human BBB, and TRPV2 was evidenced to play a main role in regulating human BBB integrity. Interspecies differences in TRPV2 and TRPV4 BBB expression complicate further preclinical validation. More studies are still needed to better establish the physiopathological TRPV roles such as in astrocytes, vascular smooth muscle cells, and pericytes. The effect of the chronic TRPV modulation should also deserve further studies to evaluate their benefit and innocuity in vivo.
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Degradable polymeric vehicles for postoperative pain management. Nat Commun 2021; 12:1367. [PMID: 33649338 PMCID: PMC7921139 DOI: 10.1038/s41467-021-21438-3] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 01/20/2021] [Indexed: 01/31/2023] Open
Abstract
Effective control of pain management has the potential to significantly decrease the need for prescription opioids following a surgical procedure. While extended release products for pain management are available commercially, the implementation of a device that safely and reliably provides extended analgesia and is sufficiently flexible to facilitate a diverse array of release profiles would serve to advance patient comfort, quality of care and compliance following surgical procedures. Herein, we review current polymeric systems that could be utilized in new, controlled post-operative pain management devices and highlight where opportunities for improvement exist.
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Abrams RMC, Pedowitz EJ, Simpson DM. A critical review of the capsaicin 8% patch for the treatment of neuropathic pain associated with diabetic peripheral neuropathy of the feet in adults. Expert Rev Neurother 2021; 21:259-266. [PMID: 33428495 DOI: 10.1080/14737175.2021.1874920] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Diabetes is an increasingly prevalent disorder affecting nearly 1-in-5 adults, of which half will experience diabetic peripheral neuropathy (DPN) and a quarter will suffer from diabetic peripheral nerve pain (DPNP), severely impacting quality of life. The currently approved treatment options are typically centrally acting agents whose use is limited by systemic effects and drug interactions. The capsaicin 8% dermal patch was recently approved by the U.S. FDA for the treatment of DPNP. AREAS COVERED The authors review the available literature regarding the use of high-concentration capsaicin 8% patch for the treatment of diabetic peripheral neuropathy and neuropathic pain and discuss implementing its use in clinical practice. EXPERT OPINION The high-concentration capsaicin 8% patch is an effective and well-tolerated treatment option for treating DPNP. Capsaicin 8% patch may be used alone or in combination with other oral therapies and can provide rapid and sustained neuropathic pain relief following a single application and is safe and effective when used long term.
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Affiliation(s)
- Rory M C Abrams
- Neurology, Mount Sinai School of Medicine, 1468 Madison Avenue, New York, NY 10019
| | - Elizabeth J Pedowitz
- Department of Geriatrics and Palliative Medicine, Mount Sinai School of Medicine, 1468 Madison Avenue, New York, 10029, NY
| | - David M Simpson
- Neurology, Mount Sinai School of Medicine, 1468 Madison Avenue, New York, NY 10019
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Fischer MJM, Ciotu CI, Szallasi A. The Mysteries of Capsaicin-Sensitive Afferents. Front Physiol 2020; 11:554195. [PMID: 33391007 PMCID: PMC7772409 DOI: 10.3389/fphys.2020.554195] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 11/13/2020] [Indexed: 12/11/2022] Open
Abstract
A fundamental subdivision of nociceptive sensory neurons is named after their unique sensitivity to capsaicin, the pungent ingredient in hot chili peppers: these are the capsaicin-sensitive afferents. The initial excitation by capsaicin of these neurons manifested as burning pain sensation is followed by a lasting refractory state, traditionally referred to as "capsaicin desensitization," during which the previously excited neurons are unresponsive not only to capsaicin but a variety of unrelated stimuli including noxious heat. The long sought-after capsaicin receptor, now known as TRPV1 (transient receptor potential cation channel, subfamily V member 1), was cloned more than two decades ago. The substantial reduction of the inflammatory phenotype of Trpv1 knockout mice has spurred extensive efforts in the pharmaceutical industry to develop small molecule TRPV1 antagonists. However, adverse effects, most importantly hyperthermia and burn injuries, have so far prevented any compounds from progressing beyond Phase 2. There is increasing evidence that these limitations can be at least partially overcome by approaches outside of the mainstream pharmaceutical development, providing novel therapeutic options through TRPV1. Although ablation of the whole TRPV1-expressing nerve population by high dose capsaicin, or more selectively by intersectional genetics, has allowed researchers to investigate the functions of capsaicin-sensitive afferents in health and disease, several "mysteries" remain unsolved to date, including the molecular underpinnings of "capsaicin desensitization," and the exact role these nerves play in thermoregulation and heat sensation. This review tries to shed some light on these capsaicin mechanisms.
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Affiliation(s)
- Michael J. M. Fischer
- Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Cosmin I. Ciotu
- Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Arpad Szallasi
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
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Perin P, Mabou Tagne A, Enrico P, Marino F, Cosentino M, Pizzala R, Boselli C. Cannabinoids, Inner Ear, Hearing, and Tinnitus: A Neuroimmunological Perspective. Front Neurol 2020; 11:505995. [PMID: 33329293 PMCID: PMC7719758 DOI: 10.3389/fneur.2020.505995] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Accepted: 08/18/2020] [Indexed: 12/14/2022] Open
Abstract
Cannabis has been used for centuries for recreational and therapeutic purposes. Whereas, the recreative uses are based on the psychotropic effect of some of its compounds, its therapeutic effects range over a wide spectrum of actions, most of which target the brain or the immune system. Several studies have found cannabinoid receptors in the auditory system, both at peripheral and central levels, thus raising the interest in cannabinoid signaling in hearing, and especially in tinnitus, which is affected also by anxiety, memory, and attention circuits where cannabinoid effects are well described. Available studies on animal models of tinnitus suggest that cannabinoids are not likely to be helpful in tinnitus treatment and could even be harmful. However, the pharmacology of cannabinoids is very complex, and most studies focused on neural CB1R-based responses. Cannabinoid effects on the immune system (where CB2Rs predominate) are increasingly recognized as essential in understanding nervous system pathological responses, and data on immune cannabinoid targets have emerged in the auditory system as well. In addition, nonclassical cannabinoid targets (such as TRP channels) appear to play an important role in the auditory system as well. This review will focus on neuroimmunological mechanisms for cannabinoid effects and their possible use as protective and therapeutic agents in the ear and auditory system, especially in tinnitus.
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Affiliation(s)
- Paola Perin
- Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy
| | | | | | | | | | - Roberto Pizzala
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Cinzia Boselli
- Department of Drug Sciences, University of Pavia, Pavia, Italy
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Abboud C, Duveau A, Bouali-Benazzouz R, Massé K, Mattar J, Brochoire L, Fossat P, Boué-Grabot E, Hleihel W, Landry M. Animal models of pain: Diversity and benefits. J Neurosci Methods 2020; 348:108997. [PMID: 33188801 DOI: 10.1016/j.jneumeth.2020.108997] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 11/03/2020] [Accepted: 11/08/2020] [Indexed: 12/15/2022]
Abstract
Chronic pain is a maladaptive neurological disease that remains a major health problem. A deepening of our knowledge on mechanisms that cause pain is a prerequisite to developing novel treatments. A large variety of animal models of pain has been developed that recapitulate the diverse symptoms of different pain pathologies. These models reproduce different pain phenotypes and remain necessary to examine the multidimensional aspects of pain and understand the cellular and molecular basis underlying pain conditions. In this review, we propose an overview of animal models, from simple organisms to rodents and non-human primates and the specific traits of pain pathologies they model. We present the main behavioral tests for assessing pain and investing the underpinning mechanisms of chronic pathological pain. The validity of animal models is analysed based on their ability to mimic human clinical diseases and to predict treatment outcomes. Refine characterization of pathological phenotypes also requires to consider pain globally using specific procedures dedicated to study emotional comorbidities of pain. We discuss the limitations of pain models when research findings fail to be translated from animal models to human clinics. But we also point to some recent successes in analgesic drug development that highlight strategies for improving the predictive validity of animal models of pain. Finally, we emphasize the importance of using assortments of preclinical pain models to identify pain subtype mechanisms, and to foster the development of better analgesics.
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Affiliation(s)
- Cynthia Abboud
- Univ. Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, F-33000 Bordeaux, France; Univ. Bordeaux, CNRS, Institute for Neurodegenerative Diseases, IMN, UMR 5293, F-33000 Bordeaux, France; Faculty of Arts and Sciences, Holy Spirit University of Kaslik (USEK), Lebanon
| | - Alexia Duveau
- Univ. Bordeaux, CNRS, Institute for Neurodegenerative Diseases, IMN, UMR 5293, F-33000 Bordeaux, France
| | - Rabia Bouali-Benazzouz
- Univ. Bordeaux, CNRS, Institute for Neurodegenerative Diseases, IMN, UMR 5293, F-33000 Bordeaux, France
| | - Karine Massé
- Univ. Bordeaux, CNRS, Institute for Neurodegenerative Diseases, IMN, UMR 5293, F-33000 Bordeaux, France
| | - Joseph Mattar
- School of Medicine and Medical Sciences, Holy Spirit University of Kaslik (USEK), Lebanon
| | - Louison Brochoire
- Univ. Bordeaux, CNRS, Institute for Neurodegenerative Diseases, IMN, UMR 5293, F-33000 Bordeaux, France
| | - Pascal Fossat
- Univ. Bordeaux, CNRS, Institute for Neurodegenerative Diseases, IMN, UMR 5293, F-33000 Bordeaux, France
| | - Eric Boué-Grabot
- Univ. Bordeaux, CNRS, Institute for Neurodegenerative Diseases, IMN, UMR 5293, F-33000 Bordeaux, France
| | - Walid Hleihel
- School of Medicine and Medical Sciences, Holy Spirit University of Kaslik (USEK), Lebanon; Faculty of Arts and Sciences, Holy Spirit University of Kaslik (USEK), Lebanon
| | - Marc Landry
- Univ. Bordeaux, CNRS, Institute for Neurodegenerative Diseases, IMN, UMR 5293, F-33000 Bordeaux, France.
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Pharmacotherapy for Small Fiber Neuropathy. Curr Treat Options Neurol 2020. [DOI: 10.1007/s11940-020-00652-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Huygen F, Kern KU, Pérez C. Expert Opinion: Exploring the Effectiveness and Tolerability of Capsaicin 179 mg Cutaneous Patch and Pregabalin in the Treatment of Peripheral Neuropathic Pain. J Pain Res 2020; 13:2585-2597. [PMID: 33116801 PMCID: PMC7569173 DOI: 10.2147/jpr.s263054] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 07/31/2020] [Indexed: 11/23/2022] Open
Abstract
Background and Objective Treatment of peripheral neuropathic pain (PNP) remains a challenge. In the absence of clear predictors of response, clinical decision-making involves trial and error. While many classes of pharmacological agent are used and have shown efficacy, one of the most commonly used first-line treatments is pregabalin. However, in the 60% of PNP cases in which the pain is localized, a local treatment may be more suitable. This article will summarize the evidence for the relative effectiveness and tolerability of the capsaicin 179 mg patch and pregabalin in the treatment of PNP and highlight the expert opinion of the authors based on their own clinical experiences. Results When compared in a head-to-head trial in patients with PNP, capsaicin 179 mg patch provided non-inferior pain relief compared with an optimized dose of pregabalin, as well as a reduction in dynamic mechanical allodynia, faster onset of action, fewer systemic side effects, and greater treatment satisfaction. Adverse events associated with capsaicin patch are mainly application site reactions, compared with systemic and central nervous system effects with pregabalin. Studies indicate that capsaicin 179 mg patch is associated with a lower burden of therapy than pregabalin in terms of improved tolerability, lack of a daily pill burden, lack of drug-drug interactions, and increased regimen flexibility. Conclusion In localized neuropathic pain, evidence supports a pragmatic approach of using a local treatment before considering a systemic treatment. For treatment selection, the patient profile (eg, concomitant medication use, age) and the treatments' efficacy and tolerability profiles should be considered.
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Affiliation(s)
- Frank Huygen
- Department of Anesthesiology, Erasmus University Medical Centre, Rotterdam, the Netherlands
| | - Kai-Uwe Kern
- Institute for Pain Medicine/Pain Practice Wiesbaden, Wiesbaden, Germany
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Kolonko AK, Efing J, González-Espinosa Y, Bangel-Ruland N, van Driessche W, Goycoolea FM, Weber WM. Capsaicin-Loaded Chitosan Nanocapsules for wtCFTR-mRNA Delivery to a Cystic Fibrosis Cell Line. Biomedicines 2020; 8:E364. [PMID: 32962254 PMCID: PMC7554911 DOI: 10.3390/biomedicines8090364] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 09/16/2020] [Accepted: 09/18/2020] [Indexed: 12/24/2022] Open
Abstract
Cystic fibrosis (CF), a lethal hereditary disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene coding for an epithelial chloride channel, is characterized by an imbalanced homeostasis of ion and water transports in secretory epithelia. As the disease is single-gene based, transcript therapy using therapeutic mRNA is a promising concept of treatment in order to correct many aspects of the fatal pathology on a cellular level. Hence, we developed chitosan nanocapsules surface-loaded with wtCFTR-mRNA to restore CFTR function. Furthermore, we loaded the nanocapsules with capsaicin, aiming to enhance the overall efficiency of transcript therapy by reducing sodium hyperabsorption by the epithelial sodium channel (ENaC). Dynamic light scattering with non-invasive back scattering (DLS-NIBS) revealed nanocapsules with an average hydrodynamic diameter of ~200 nm and a Zeta potential of ~+60 mV. The results of DLS-NIBS measurements were confirmed by asymmetric flow field-flow fractionation (AF4) with multidetection, while transmission electron microscopy (TEM) images confirmed the spherical morphology and size range. After stability measurements showed that the nanocapsules were highly stable in cell culture transfection medium, and cytotoxicity was ruled out, transfection experiments were performed with the CF cell line CFBE41o-. Finally, transepithelial measurements with a new state-of-the-art Ussing chamber confirmed successfully restored CFTR function in transfected cells. This study demonstrates that CS nanocapsules as a natural and non-toxic delivery system for mRNA to target cells could effectively replace risky vectors for gene delivery. The nanocapsules are not only suitable as a transcript therapy for treatment of CF, but open aspiring possibilities for safe gene delivery in general.
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Affiliation(s)
- A. Katharina Kolonko
- Institute of Animal Physiology, University of Muenster, Schlossplatz 8, 48143 Muenster, Germany; (J.E.); (N.B.-R.); (W.-M.W.)
| | - Janes Efing
- Institute of Animal Physiology, University of Muenster, Schlossplatz 8, 48143 Muenster, Germany; (J.E.); (N.B.-R.); (W.-M.W.)
| | - Yadira González-Espinosa
- School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK; (Y.G.-E.); (F.M.G.)
| | - Nadine Bangel-Ruland
- Institute of Animal Physiology, University of Muenster, Schlossplatz 8, 48143 Muenster, Germany; (J.E.); (N.B.-R.); (W.-M.W.)
| | | | - Francisco M. Goycoolea
- School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK; (Y.G.-E.); (F.M.G.)
| | - Wolf-Michael Weber
- Institute of Animal Physiology, University of Muenster, Schlossplatz 8, 48143 Muenster, Germany; (J.E.); (N.B.-R.); (W.-M.W.)
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Bonezzi C, Costantini A, Cruccu G, Fornasari DMM, Guardamagna V, Palmieri V, Polati E, Zini P, Dickenson AH. Capsaicin 8% dermal patch in clinical practice: an expert opinion. Expert Opin Pharmacother 2020; 21:1377-1387. [PMID: 32511032 DOI: 10.1080/14656566.2020.1759550] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 04/20/2020] [Indexed: 01/11/2023]
Abstract
INTRODUCTION Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system, which can severely impact patients' quality of life. The current-approved treatments for NP comprise of both centrally acting agents and topical drugs, including capsaicin 8% dermal patches, which is approved for the treatment of peripheral NP. AREAS COVERED The authors summarize literature data regarding capsaicin use in patients who suffer from NP and discuss the clinical applications of this topical approach. EXPERT OPINION Overall, the capsaicin 8% dermal patch is as effective in reducing pain intensity as other centrally active agents (i.e. pregabalin). Some studies have also reported fewer systemic side effects, a faster onset of action and superior treatment satisfaction compared with systemic agents. In our opinion, capsaicin 8% dermal patches also present additional advantages, such as a good systemic tolerability, the scarcity of adverse events, the possibility to combine it with other agents, and a good cost-effective profile. It is important to note that, as the mechanism of action of capsaicin 8% is the 'defunctionalization' of small afferent fibers through interaction with TRPV1 receptors, the peripheral expression of this receptor on nociceptor fibers, is crucial to predict patient's response to treatment.
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Affiliation(s)
- Cesare Bonezzi
- Pain Therapy Unit, Istituti Clinici Scientifici Maugeri , Pavia, Italy
| | | | - Giorgio Cruccu
- Department of Human Neurosciences, "Sapienza" University of Rome , Rome, Italy
| | - Diego M M Fornasari
- Department of Medical Biotechnology and Translational Medicine, University of Milan , Milan, Italy
| | - Vittorio Guardamagna
- Palliative Care and Pain Therapy Division, IRCCS European Institute of Oncology (IEO) , Milan, Italy
| | - Vincenzo Palmieri
- Pain Therapy and Palliative Care Unit, Gaetano Rummo Hospital , Benevento, Italy
| | - Enrico Polati
- Anestesia E Rianimazione, Terapia del Dolore. Azienda Ospedaliera Universitaria Integrata di Verona , Verona, Italy
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Thomas SE, Laycock H. The use of high dose topical capsaicin in the management of peripheral neuropathy: narrative review and local experience. Br J Pain 2020; 14:133-140. [PMID: 32537152 DOI: 10.1177/2049463720914332] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Capsaicin, derived from the chilli pepper plant, is available in high concentration (8%) patches to provide topical therapy for neuropathic pain. Its analgesic effects relate to defunctionalisation and nerve terminal retraction of predominantly C fibres in the dermis and epidermis. Systematic reviews and meta-analysis support its use for the management of post-herpetic neuralgia and HIV neuropathy with some evidence for use in painful peripheral diabetic neuropathy. The article concludes with advice on the practicalities of running a topical 8% capsaicin clinic for peripheral neuropathic pain.
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Tang K, Zhang X, Guo Y. Identification of the dietary supplement capsaicin as an inhibitor of Lassa virus entry. Acta Pharm Sin B 2020; 10:789-798. [PMID: 32528827 PMCID: PMC7276894 DOI: 10.1016/j.apsb.2020.02.014] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 02/19/2020] [Accepted: 02/25/2020] [Indexed: 12/16/2022] Open
Abstract
The limited treatment options for the increasing occurrence of Lassa hemorrhagic fever in West Africa poses an urgent need for the discovery and development of novel therapeutics. Dietary supplements, especially natural products that are edible and safe for human use, are a good source of drug discovery with potential for uncovering novel applications. In this study, we tested 40 natural products of dietary supplements and identified capsaicin, a common dietary supplement abundant in chili peppers, as an inhibitor of Lassa virus (LASV) entry with EC50 of 6.9-10.0 μmol/L using an HIV based pseudovirus platform. Capsaicin inhibits the entry of five LASV strains but not against the Old World arenavirus lymphocytic choriomeningitis virus (LCMV), showing a preferential activity against LASV. Capsaicin inhibits LASV entry by blocking the pH dependent viral fusion through affecting the stable signal peptide (SSP)-GP2 transmembrane (GP2TM) region of the LASV surface glycoprotein. Mutational study revealed the key residues Ala25, Val431, Phe434 and Val435 in SSP-GP2TM region in capsaicin's antiviral effect. This study for the first time reveals a direct acting antiviral effect of capsaicin against the hemorrhagic fever causing LASV, providing detailed interaction hot spots in the unique SSP-GP2TM interface of LASV glycoprotein that is crucial in fusion inhibition, and offering a new strategy in discovering and developing antivirals from natural products that are safe for human use.
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Affiliation(s)
- Ke Tang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Xiaoyu Zhang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Ying Guo
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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Liu L, Gu L, Chen M, Zheng Y, Xiong X, Zhu S. Novel Targets for Stroke Therapy: Special Focus on TRPC Channels and TRPC6. Front Aging Neurosci 2020; 12:70. [PMID: 32256338 PMCID: PMC7093711 DOI: 10.3389/fnagi.2020.00070] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 02/26/2020] [Indexed: 12/14/2022] Open
Abstract
Stroke remains a leading cause of death, disability, and medical care burden worldwide. However, transformation from laboratory findings toward effective pharmacological interventions for clinical stroke has been unsatisfactory. Novel evidence has been gained on the underlying mechanisms and therapeutic potential related to the transient receptor potential (TRP) channels in several disorders. The TRP superfamily consists of a diverse group of Ca2+ permeable non-selective cation channels. In particular, the members of TRP subfamilies, TRP canonical (TRPC) channels and TRPC6, have been found in different cell types in the whole body and have high levels of expression in the central nervous system (CNS). Notably, the TRPCs and TRPC6 channel have been implicated in neurite outgrowth and neuronal survival during normal development and in a range of CNS pathological conditions. Recent studies have shown that suppression of TRPC6 channel degradation prevents ischemic neuronal cell death in experimental stroke. Accumulating evidence supports the important functions of TRPC6 in brain ischemia. We have highlighted some crucial advancement that points toward an important involvement of TRPCs and TRPC6 in ischemic stroke. This review will make an overview of the TRP and TRPC channels due to their roles as targets for clinical trials and CNS disorders. Besides, the primary goal is to discuss and update the critical role of TRPC6 channels in stroke and provide a promising target for stroke prevention and therapy.
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Affiliation(s)
- Lu Liu
- Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lijuan Gu
- Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China
| | - Manli Chen
- Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yueying Zheng
- Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaoxing Xiong
- Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China
| | - Shengmei Zhu
- Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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50
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Abstract
Introduction: Treatment for chronic pruritus ranges from use of topical formulations to newer biologic agents. Targeting treatment to the underlying etiology is key in reducing the burden of disease while avoiding systemic or adverse effects.Areas covered: This review details the effective medical treatments used in various etiologies of chronic itch with a focus on the potential adverse effects and safety data available for each.Expert opinion: New drug developments in the areas of neural signaling and immune targeting show great promise for the future of chronic itch treatment. These new therapies broaden the available treatment options but also pose new considerations for safety and adverse effects.
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Affiliation(s)
- Kayla Fourzali
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery and Miami Itch Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Gil Yosipovitch
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery and Miami Itch Center, University of Miami Miller School of Medicine, Miami, FL, USA
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