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Oka T, Kawamura T, Shirasaka W. Differences in acute phase pain characteristics between patients undergoing bipolar hip arthroplasty versus open reduction internal fixation for hip fracture. Arch Orthop Trauma Surg 2025; 145:304. [PMID: 40392356 DOI: 10.1007/s00402-025-05916-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Accepted: 05/05/2025] [Indexed: 05/22/2025]
Abstract
INTRODUCTION/OBJECTIVES Patients who experience hip fractures often undergo bipolar hip arthroplasty (BHA) or open reduction and internal fixation (ORIF); however, acute postoperative pain remains a significant concern, often delaying rehabilitation and impairing recovery. This study compared acute phase pain characteristics (intensity and trajectory, and duration of analgesic use) between BHA and ORIF. Previous studies have suggested that patients undergoing ORIF may experience higher pain levels than those undergoing BHA, although most assessments have been limited to single time points, which may not capture the full scope of postoperative pain. MATERIALS AND METHODS This prospective cohort study was conducted between February and August 2024. Pain intensity was evaluated on postoperative day (POD) 1, 3, 5, 7, and 14 using a numerical rating scale. Pain trajectories (slope and intercept) were calculated based on pain intensity assessed on POD 1, 3, 5, and 7. The duration of analgesia was assessed from the time of surgery until discontinuation. Multiple linear regression analysis was performed to examine the effect of surgical type (0, BHA; 1, ORIF) on pain-related outcomes, adjusting for confounders including age, sex, preoperative C-reactive protein level, and operative duration. RESULTS Data from 48 patients who underwent BHA and 32 who underwent ORIF were analyzed. There were no significant differences in pain intensity between the groups on POD 1 and 3. However, pain was significantly greater in the ORIF group on POD 5 (p < 0.01), 7 (p < 0.01), and 14 (p < 0.01). Regression analysis revealed that surgery type significantly influenced pain intensity on POD 14 (β = 1.27, p = 0.01) and pain trajectory slope (β = 0.52, p = 0.03). The intercept and analgesic duration were not significantly different between the groups. CONCLUSIONS Acute phase postoperative pain characteristics differed between BHA and ORIF, highlighting the need for targeted pain management during recovery in patients undergoing ORIF.
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MESH Headings
- Humans
- Male
- Female
- Hip Fractures/surgery
- Pain, Postoperative/etiology
- Pain, Postoperative/drug therapy
- Pain, Postoperative/diagnosis
- Arthroplasty, Replacement, Hip/methods
- Arthroplasty, Replacement, Hip/adverse effects
- Prospective Studies
- Aged
- Open Fracture Reduction/adverse effects
- Open Fracture Reduction/methods
- Fracture Fixation, Internal/methods
- Fracture Fixation, Internal/adverse effects
- Pain Measurement
- Acute Pain/etiology
- Acute Pain/diagnosis
- Middle Aged
- Aged, 80 and over
- Analgesics/therapeutic use
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Affiliation(s)
- Tomohiro Oka
- Department of Physical Therapy, Osaka Health Science University, Osaka, Japan.
- Department of Public Health, Kobe University Graduate School of Health Sciences, Kobe, Japan.
| | - Tomonori Kawamura
- Department of Physical Therapy, Morinomiya University of Medical Sciences, Osaka city, Japan
- Department of Rehabilitation, Kishiwada Tokushukai Hospital, Osaka, Japan
| | - Wataru Shirasaka
- Department of Orthopedics, Kishiwada Tokushukai Hospital, Osaka, Japan
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Nishiwaki T, Ishikura H, Masuyama Y, Fujita S, Hirose R. Impact of preoperative factors on clinical outcomes after total hip arthroplasty. World J Orthop 2025; 16:105273. [PMID: 40290605 PMCID: PMC12019137 DOI: 10.5312/wjo.v16.i4.105273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 03/05/2025] [Accepted: 03/31/2025] [Indexed: 04/17/2025] Open
Abstract
BACKGROUND Although total hip arthroplasty (THA) is an established intervention for advanced hip disorders, not all patients achieve the anticipated functional improvements. AIM To investigate the impact of various preoperative factors on clinical outcomes after THA. METHODS Data of 411 patients who underwent unilateral THA were retrospectively analyzed. The associations between preoperative factors, such as age, body mass index, pain severity, functional impairment, psychological status, neuropathic pain, and central sensitization, and clinical outcomes assessed six months postoperatively using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and modified Harris Hip Score were evaluated. RESULTS Our results indicated that age and the WOMAC, Center for Epidemiologic Studies Depression Scale, and Central Sensitization Index (CSI) scores significantly predicted the modified Harris Hip Score outcomes, whereas age and preoperative WOMAC, EuroQol 5 dimensions, Center for Epidemiologic Studies Depression Scale, CSI, and Pain Detect Questionnaire scores were significant predictors of WOMAC outcomes. Age, WOMAC, and CSI were consistently significant factors. There were no significant differences in the operative time or blood loss across the outcome categories. CONCLUSION Our findings highlight the importance of preoperative assessment of central sensitization and psychological parameters. Patient-specific preoperative characteristics may play a greater role than intraoperative factors in determining recovery outcomes after THA.
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Affiliation(s)
- Toru Nishiwaki
- Department of Orthopaedic Surgery, Shizuoka Red Cross Hospital, Shizuoka 420-0853, Japan
| | - Hisatoshi Ishikura
- Department of Orthopaedic Surgery, Shizuoka Red Cross Hospital, Shizuoka 420-0853, Japan
| | - Yuji Masuyama
- Department of Orthopaedic Surgery, Shizuoka Red Cross Hospital, Shizuoka 420-0853, Japan
| | - Sho Fujita
- Department of Orthopaedic Surgery, Shizuoka Red Cross Hospital, Shizuoka 420-0853, Japan
| | - Rei Hirose
- Department of Orthopaedic, Shizuoka Red Cross Hospital, Shizuoka 420-0853, Japan
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Tamura S, Miura S, Matsuda R. Prediction of Chronic Fracture Pain in Patients with Osteoporotic Fractures Using the Japanese Short-form Central Sensitization Inventory: A Single-center Retrospective Observational Study in a Convalescent Rehabilitation Ward. Phys Ther Res 2025; 28:22-30. [PMID: 40321690 PMCID: PMC12047042 DOI: 10.1298/ptr.e10312] [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: 08/16/2024] [Accepted: 11/27/2024] [Indexed: 05/08/2025]
Abstract
OBJECTIVES Chronic fracture pain (CFP) is a significant issue in patients with osteoporotic fractures (OFs) in convalescent rehabilitation wards (CRWs). This study aimed to examine the association between CFP and the Japanese short-form Central Sensitization Inventory (CSI-9) and verify the predictive validity of CSI-9 in patients with OF admitted to a CRW. METHODS This single-center retrospective study included 71 patients with OF (median age: 85.3 years, 54 females). CFP was defined as pain of Numerical Rating Scale (NRS) score ≥4 persisting at discharge, despite >3 months post-fracture. Multiple logistic regression and receiver operating characteristic curve analyses were performed to assess the association and predictive validity of the CSI-9 for CFP. RESULTS The incidence of CFP was 38.0%. CSI-9 was independently associated with CFP at admission (odds ratio = 1.12, 95% confidence interval [CI]: 1.01-1.24) and discharge (odds ratio = 1.15, 95% CI: 1.03-1.29). The area under the curve for the CSI-9 was 0.727 (95% CI: 0.605-0.850) at admission and 0.752 (95% CI: 0.637-0.867) at discharge, indicating fair predictive accuracy. The optimal cutoff values for the CSI-9 were 8 points at admission and 6 points at discharge. CONCLUSIONS CSI-9 was independently associated with CFP and demonstrated moderate predictive accuracy in patients with OF in CRWs. Assessing central sensitization-related symptoms using the CSI-9 may be useful for evaluating and preventing CFP in this population. Further validation using large-scale prospective studies is required.
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Affiliation(s)
- Shotaro Tamura
- Department of Rehabilitation, IMS Group IMS Sapporo Internal Medicine Rehabilitation Hospital, Japan
| | - Sayo Miura
- Department of Rehabilitation, Japan Health Care College, Japan
| | - Ryo Matsuda
- Department of Physical Therapy, Faculty of Health Sciences, Hokkaido University of Science, Japan
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Desai MJ, Brestle M, Jonely H. Evidence for central sensitization as classified by the central sensitization inventory in patients with pain and hypermobility. Pain Pract 2025; 25:e13411. [PMID: 39192465 DOI: 10.1111/papr.13411] [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] [Indexed: 08/29/2024]
Abstract
INTRODUCTION Pain is a very common complaint among patients with hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders (HSDs). Often challenging to treat, insights into the underpinnings of pain in this population have been fleeting. Central sensitization (CS) has been postulated as a potential etiological factor. METHODS In this retrospective study, 82 consecutive patients with hEDS/HSDs were reviewed. Demographic information and Central Sensitization Inventory (CSI) results were collected. RESULTS 71 of 82 (86.5%) patients demonstrated CS. Scores ranged from 12 to 94 with a median of 56. Pain scores as measured on the numerical rating scale (NRS) ranged from 2 to 10 with a mean and median of 6. CONCLUSION A large percentage of patients with pain and a diagnosis of hEDS/HSDs demonstrated evidence of central sensitization as measured using the CSI. The CSI is simple to administer. The CSI may provide clinical insights that are key to successfully managing patients with hEDS/HSDs. Further research is needed to explore the ability to classify pain phenotypes in this patient population and the impact on precision medicine.
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Affiliation(s)
- Mehul J Desai
- International Spine, Pain & Performance Center, Washington, District of Columbia, USA
- George Washington University, School of Medicine and Health Sciences, Washington, District of Columbia, USA
| | - Mason Brestle
- International Spine, Pain & Performance Center, Washington, District of Columbia, USA
- Philadelphia College of Osteopathic Medicine, Suwanee, Georgia, USA
| | - Holly Jonely
- International Spine, Pain & Performance Center, Washington, District of Columbia, USA
- The University of Oklahoma, College of Allied Health, Oklahoma City, Oklahoma, USA
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Tsuchiya M, Ohashi Y, Fukushima K, Okuda Y, Suto A, Matsui T, Kodera Y, Sato M, Tsukada A, Inoue G, Takaso M, Uchida K. Fibrocyte Phenotype of ENTPD1+CD55+ Cells and Its Association with Pain in Osteoarthritic Synovium. Int J Mol Sci 2024; 25:4085. [PMID: 38612896 PMCID: PMC11012446 DOI: 10.3390/ijms25074085] [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] [Received: 03/13/2024] [Revised: 03/29/2024] [Accepted: 04/04/2024] [Indexed: 04/14/2024] Open
Abstract
Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage erosion, structural changes, and inflammation. Synovial fibroblasts play a crucial role in OA pathophysiology, with abnormal fibroblastic cells contributing significantly to joint pathology. Fibrocytes, expressing markers of both hematopoietic and stromal cells, are implicated in inflammation and fibrosis, yet their marker and role in OA remain unclear. ENTPD1, an ectonucleotidase involved in purinergic signaling and expressed in specific fibroblasts in fibrotic conditions, led us to speculate that ENTPD1 plays a role in OA pathology by being expressed in fibrocytes. This study aimed to investigate the phenotype of ENTPD1+CD55+ and ENTPD1-CD55+ synovial fibroblasts in OA patients. Proteomic analysis revealed a distinct molecular profile in ENTPD1+CD55+ cells, including the upregulation of fibrocyte markers and extracellular matrix-related proteins. Pathway analysis suggested shared mechanisms between OA and rheumatoid arthritis. Correlation analysis revealed an association between ENTPD1+CD55+ fibrocytes and resting pain in OA. These findings highlight the potential involvement of ENTPD1 in OA pain and suggest avenues for targeted therapeutic strategies. Further research is needed to elucidate the underlying molecular mechanisms and validate potential therapeutic targets.
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Affiliation(s)
- Maho Tsuchiya
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara 252-0374, Japan; (M.T.); (Y.O.); (K.F.); (A.T.); (G.I.); (M.T.)
| | - Yoshihisa Ohashi
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara 252-0374, Japan; (M.T.); (Y.O.); (K.F.); (A.T.); (G.I.); (M.T.)
| | - Kensuke Fukushima
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara 252-0374, Japan; (M.T.); (Y.O.); (K.F.); (A.T.); (G.I.); (M.T.)
| | - Yusei Okuda
- Department of Physics, School of Science, Kitasato University, Sagamihara 252-0373, Japan; (Y.O.); (A.S.); (T.M.); (Y.K.)
| | - Arisa Suto
- Department of Physics, School of Science, Kitasato University, Sagamihara 252-0373, Japan; (Y.O.); (A.S.); (T.M.); (Y.K.)
| | - Takashi Matsui
- Department of Physics, School of Science, Kitasato University, Sagamihara 252-0373, Japan; (Y.O.); (A.S.); (T.M.); (Y.K.)
- Center for Disease Proteomics, School of Science, Kitasato University, Sagamihara 252-0373, Japan
| | - Yoshio Kodera
- Department of Physics, School of Science, Kitasato University, Sagamihara 252-0373, Japan; (Y.O.); (A.S.); (T.M.); (Y.K.)
- Center for Disease Proteomics, School of Science, Kitasato University, Sagamihara 252-0373, Japan
| | - Masashi Sato
- Department of Immunology, Kitasato University School of Medicine, Sagamihara 252-0374, Japan;
| | - Ayumi Tsukada
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara 252-0374, Japan; (M.T.); (Y.O.); (K.F.); (A.T.); (G.I.); (M.T.)
| | - Gen Inoue
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara 252-0374, Japan; (M.T.); (Y.O.); (K.F.); (A.T.); (G.I.); (M.T.)
| | - Masashi Takaso
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara 252-0374, Japan; (M.T.); (Y.O.); (K.F.); (A.T.); (G.I.); (M.T.)
| | - Kentaro Uchida
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara 252-0374, Japan; (M.T.); (Y.O.); (K.F.); (A.T.); (G.I.); (M.T.)
- Research Institute, Shonan University of Medical Sciences, Chigasaki 253-0083, Japan
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Lang-Illievich K, Lang J, Rumpold-Seitlinger G, Dorn C, Brenna CTA, Klivinyi C, Bornemann-Cimenti H. The Dose-Response Relationship between Opioid Agonist Therapy and Alterations in Pain Pathways in Patients with Opioid Use Disorders: A Cross-Sectional Study. CNS Drugs 2024; 38:281-290. [PMID: 38421579 PMCID: PMC10980620 DOI: 10.1007/s40263-024-01069-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/04/2024] [Indexed: 03/02/2024]
Abstract
INTRODUCTION The administration of opioids can be followed by enduring neuroplastic changes in the peripheral and central nervous systems. This remodeling can lead to opioid-induced hyperalgesia, causing an increased sensitivity to painful stimuli. The description of opioid-induced changes in the somatosensory system has seldom been described in the setting of opioid agonist therapy in the treatment of opioid use disorders, and the few existing reports provide no guidance with respect to the effect of varied doses or substances. OBJECTIVE The aim of the present study was to assess alterations of pain pathways among patients receiving opioid agonist therapy and to elucidate the dose-response relationship. METHODS This study was planned as cross-sectional in an outpatient clinic in Graz, Austria. Patients receiving opioid agonist therapy for opioid use disorders (including methadone, levomethadone, buprenorphine, and extended-release morphine) were asked to fill out a questionnaire, including the central sensitization inventory. A battery of somatosensory system assessments was then performed. RESULTS A total of 120 patients participated (85 men/35 women). The mean oral morphine milligram equivalent (MME) was 694 ± 249 mg/day. Our study found significant alterations in pain perception, conditioned pain modulation, and wind-up. We demonstrated a moderate dose-response relationship between high-dose opioids and markers of central sensitization. CONCLUSION The present trial demonstrates the clear effects of opioid agonist therapy on the somatosensory system. Both central sensitization and descending pain modulation are negatively affected by high doses of opioids and our data elucidate a moderate dose-response relationship for these phenomena.
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Affiliation(s)
- Kordula Lang-Illievich
- Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Auenbruggerplatz 5/5, 8036, Graz, Austria
- Department of Anesthesia and Intensive Care Medicine, Klinik Güssing, Güssing, Austria
| | - Johanna Lang
- Comenius University Bratislava, Bratislava, Slovakia
| | - Gudrun Rumpold-Seitlinger
- Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Auenbruggerplatz 5/5, 8036, Graz, Austria
| | - Christian Dorn
- Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Auenbruggerplatz 5/5, 8036, Graz, Austria
| | - Connor T A Brenna
- Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada
| | - Christoph Klivinyi
- Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Auenbruggerplatz 5/5, 8036, Graz, Austria
| | - Helmar Bornemann-Cimenti
- Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Auenbruggerplatz 5/5, 8036, Graz, Austria.
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Sahin T, Sacaklidir R, Sancar M, Öztürk EC. The effect of human assumed central sensitization on transforaminal epidural steroid injection in chronic lumbar radiculopathy: An observational study. J Back Musculoskelet Rehabil 2024; 37:1749-1755. [PMID: 39213049 PMCID: PMC11613053 DOI: 10.3233/bmr-240231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 07/25/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Human assumed central sensitization (HACS) is a potential pathophysiological mechanism underlying a group of musculoskeletal disorders. HACS may negatively influence the outcomes of surgical or interventional procedures. OBJECTIVE The present study aimed to investigate the impact of HACS on treatment outcomes of transforaminal epidural steroid injection (TFESI). METHODS Patients who received fluoroscopy-guided single-level lumbosacral TFESI between January 2020 and January 2021 were included in the study. The patients were divided into two groups with respect to the existence of HACS. Patients were assessed before the procedure, at the third week, and at the third month after the procedure. The presence of HACS was investigated by central sensitization inventory (CSI). The Numerical Rating Scale (NRS), Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI) were used for patient assessment. RESULTS A total of 65 patients were included in the study. Thirty-one of the patients had HACS. There was no difference between the groups in terms of demographic data. Significant improvement in NRS was found at 3rd week and 3rd month compared to the baseline. BDI and ODI scores were also significantly reduced at the end of 3 months (p< 0.001). NRS scores at all time points were significantly lower in patients without HACS (p< 0.05). CONCLUSION The presence of HACS has a negative effect on pain scores, disability, and mental state in patients undergoing TFESI.
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Affiliation(s)
- Tülay Sahin
- Pain Management Section, Department of Physical Medicine and Rehabilitation, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey
| | - Rekib Sacaklidir
- Pain Management Section, Department of Physical Medicine and Rehabilitation, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey
| | - Mert Sancar
- Physical Medicine and Rehabilitation, Istanbul Medicine Hospital, Istanbul, Turkey
| | - Ekim Can Öztürk
- Pain Medicine Section, Department of Physical Medicine and Rehabilitation, Istanbul Goztepe Prof. Dr. Suleyman Yalcin City Hospital, Istanbul, Turkey
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Shumnalieva R, Kotov G, Ermencheva P, Monov S. Pathogenic Mechanisms and Therapeutic Approaches in Obesity-Related Knee Osteoarthritis. Biomedicines 2023; 12:9. [PMID: 38275369 PMCID: PMC10812969 DOI: 10.3390/biomedicines12010009] [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: 11/23/2023] [Revised: 12/10/2023] [Accepted: 12/14/2023] [Indexed: 01/27/2024] Open
Abstract
The knee is the joint most frequently involved in osteoarthritis, a common joint disorder in the adult population that is associated with significant chronic joint pain, reduced mobility and quality of life. Recent studies have established an association between obesity and the development of knee osteoarthritis that goes beyond the increased mechanical load on the knees as weight-bearing joints. This link is based on the maintenance of a chronic low-grade inflammation, altered secretion of adipokines by the adipose tissue and development of sarcopenia. Major adipokines involved in the pathogenesis of obesity-related knee osteoarthritis include adiponectin, which appears to have a protective effect, as well as leptin, resistin and visfatin, which are associated with higher pain scores and more severe structural damage. Joint pain in knee osteoarthritis may be both nociceptive and neuropathic and is the result of complex mechanisms driven by nerve growth factor, calcitonin gene-related peptide and pro-inflammatory cytokines. The role of endogenous cannabinoids and gut microbiota in common mechanisms between obesity and knee pain has recently been studied. The aim of the present review is to highlight major pathogenic mechanisms in obesity-related knee osteoarthritis with special attention on pain and to comment on possible therapeutic approaches.
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Affiliation(s)
- Russka Shumnalieva
- Department of Rheumatology, Medical University of Sofia, 1431 Sofia, Bulgaria; (R.S.); (S.M.)
- Clinic of Rheumatology, University Hospital ‘St. Ivan Rilski’, 1612 Sofia, Bulgaria;
| | - Georgi Kotov
- Department of Rheumatology, Medical University of Sofia, 1431 Sofia, Bulgaria; (R.S.); (S.M.)
- Clinic of Rheumatology, University Hospital ‘St. Ivan Rilski’, 1612 Sofia, Bulgaria;
| | - Plamena Ermencheva
- Clinic of Rheumatology, University Hospital ‘St. Ivan Rilski’, 1612 Sofia, Bulgaria;
| | - Simeon Monov
- Department of Rheumatology, Medical University of Sofia, 1431 Sofia, Bulgaria; (R.S.); (S.M.)
- Clinic of Rheumatology, University Hospital ‘St. Ivan Rilski’, 1612 Sofia, Bulgaria;
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Feng B, Gong C, You L, Lin Y, Wang Y, Ip WY, Wang Y. Central Sensitization in Patients with Chronic Pain Secondary to Carpal Tunnel Syndrome and Determinants. J Pain Res 2023; 16:4353-4366. [PMID: 38145037 PMCID: PMC10748611 DOI: 10.2147/jpr.s441786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 12/12/2023] [Indexed: 12/26/2023] Open
Abstract
Purpose Central sensitization (CS) is commonly seen in chronic pain disorders, including neuropathic pain. However, there exist inconsistencies concerning the presence of CS in chronic pain secondary to carpal tunnel syndrome (CTS). CS and neuropathic pain manifestations in CTS remain not well established. Therefore, this study aims to investigate the CS and pain profiles in patients with CTS and to explore the potential determinants associated with CS. Patients and Methods Patients with suspected CTS symptoms lasting 3 months or above and healthy controls were enrolled. History, physical examinations, and nerve conduction studies were employed to confirm the diagnosis and severity of median nerve dysfunction. The central sensitization inventory (CSI) was used to screen CS. Other outcomes included neuropathic pain, CTS-specific symptom severity and functions, emotion, and health-related quality of life. Between-group comparisons were conducted in terms of the CS presence. Logistic regression analysis was performed to identify determinants associated with CS. Results Over 60% of participants with CTS were found with clinical CS, significantly higher than that in the control group. More than 70% of the CTS participants were identified to have possible or very likely neuropathic pain components. In addition, one-fourth of CTS cases had depression or anxiety. Anxiety was associated with an increased risk of developing CS in CTS (adjusted OR=1.31, 95% CI 1.08-1.59), whereas higher self-perceived general health rating was negatively associated with the presence of CS (adjusted OR=0.92, 95% CI 0.88-0.97) in the multivariate adjusted regression model. Conclusion CS is prevalent in patients with CTS. Predominant neuropathic pain characteristics were uncovered in CTS patients as well as comorbid psychological distress. Significant association was found between anxiety and CS presence. Self-perceived general health was inversely related to CS. Further research is warranted to explore the mechanisms of anxiety and central pain processing in painful entrapment neuropathy.
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Affiliation(s)
- Beibei Feng
- Department of Rehabilitation Medicine, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
- Department of Orthopaedics & Traumatology, the University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of China
- Guangdong Provincial Clinical Research Center for Rehabilitation Medicine, Guangzhou, People’s Republic of China
- Biomedical Innovation Center, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Chen Gong
- Department of Rehabilitation Medicine, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
- Guangdong Provincial Clinical Research Center for Rehabilitation Medicine, Guangzhou, People’s Republic of China
- Biomedical Innovation Center, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Longfei You
- Department of Rehabilitation Medicine, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
- Guangdong Provincial Clinical Research Center for Rehabilitation Medicine, Guangzhou, People’s Republic of China
- Biomedical Innovation Center, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Yangyang Lin
- Department of Rehabilitation Medicine, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
- Guangdong Provincial Clinical Research Center for Rehabilitation Medicine, Guangzhou, People’s Republic of China
- Biomedical Innovation Center, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Yafei Wang
- Department of Rehabilitation Medicine, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
- Guangdong Provincial Clinical Research Center for Rehabilitation Medicine, Guangzhou, People’s Republic of China
- Biomedical Innovation Center, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Wing Yuk Ip
- Department of Orthopaedics & Traumatology, the University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of China
| | - Yuling Wang
- Department of Rehabilitation Medicine, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
- Guangdong Provincial Clinical Research Center for Rehabilitation Medicine, Guangzhou, People’s Republic of China
- Biomedical Innovation Center, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
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Iio R, Manaka T, Nakazawa K, Hirakawa Y, Ito Y, Ogura A, Nakamura H. Assessment of Prevalence and Risk Factors for Central Sensitization Related to Shoulder Osteoarthritis and Rotator Cuff Tears Using the Central Sensitization Inventory: A Cross-Sectional Study in Shoulder Surgery Patients. J Clin Med 2023; 12:5633. [PMID: 37685700 PMCID: PMC10488326 DOI: 10.3390/jcm12175633] [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: 06/19/2023] [Revised: 08/08/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023] Open
Abstract
Shoulder disorders occasionally cause intractable pain. Central sensitization (CS) may be involved in such pain. Identifying risk factors associated with CS is crucial for effective pain control. This study aimed to determine the effects of shoulder osteoarthritis and rotator cuff tears (RCT) on CS and associated factors. This study included patients evaluated for CS using the Central Sensitization Inventory (CSI) before surgery for shoulder osteoarthritis, RCT, or cuff tear arthropathy. Patients with a CSI score of 40 or higher were defined as having CS. The relationships between glenohumeral osteoarthritis (GHOA), RCT size, and CS were statistically analyzed. Multiple regression analysis was performed to examine the factors affecting CSI scores. Subjects included 167 patients: 131 patients had RCT without GHOA, 23 had GHOA with RCT, and 13 had GHOA without RCT. The GHOA group had a significantly higher CSI score (27.5 [10.8-40.5] vs. 18.0 [10.0-27.5]) and CS prevalence (27.8% vs. 8.4%) than the RCT without GHOA group. There was no significant correlation between RCT size and CSI scores. Multiple regression analysis showed that female sex, severe pain, and long pain duration were associated with higher CSI scores. Considering the risk factors for CS might be helpful in shoulder treatment.
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Affiliation(s)
- Ryosuke Iio
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan; (R.I.); (K.N.)
| | - Tomoya Manaka
- Department of Orthopaedic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan; (Y.H.); (H.N.)
| | - Katsumasa Nakazawa
- Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan; (R.I.); (K.N.)
| | - Yoshihiro Hirakawa
- Department of Orthopaedic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan; (Y.H.); (H.N.)
| | - Yoichi Ito
- Ito Clinic, Osaka Shoulder Center, Osaka 580-0016, Japan; (Y.I.); (A.O.)
| | - Ayako Ogura
- Ito Clinic, Osaka Shoulder Center, Osaka 580-0016, Japan; (Y.I.); (A.O.)
| | - Hiroaki Nakamura
- Department of Orthopaedic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan; (Y.H.); (H.N.)
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Schuttert I, Wolff AP, Schiphorst Preuper RHR, Malmberg AGGA, Reneman MF, Timmerman H. Validity of the Central Sensitization Inventory to Address Human Assumed Central Sensitization: Newly Proposed Clinically Relevant Values and Associations. J Clin Med 2023; 12:4849. [PMID: 37510964 PMCID: PMC10381378 DOI: 10.3390/jcm12144849] [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: 06/13/2023] [Revised: 07/15/2023] [Accepted: 07/20/2023] [Indexed: 07/30/2023] Open
Abstract
Central sensitization cannot be directly demonstrated in humans and thus a gold standard is missing. Therefore, we used human assumed central sensitization (HACS) when associated with humans. The central sensitization inventory (CSI) is a screening questionnaire for addressing symptoms that are associated with HACS. This cross-sectional study compared patients with chronic pain and at least one central sensitivity syndrome with healthy, pain-free controls via ROC analyses. Analyses were performed for all participants together and for each sex separately. Regression analyses were performed on patients with chronic pain with and without central sensitivity syndromes. Based on 1730 patients and 250 healthy controls, cutoff values for the CSI for the total group were established at 30 points: women: 33 points; men: 25 points. Univariate and multivariate regression analyses were used to identify possible predictors for the CSI score in 2890 patients with chronic pain. The CSI score is associated with all independent factors and has a low association with pain severity in women and a low association with pain severity, age, and body mass index in men. The newly established CSI cutoff values are lower than in previous studies and different per sex, which might be of clinical relevance in daily practice and importance in research.
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Affiliation(s)
- Ingrid Schuttert
- Pain Center, Department of Anaesthesiology, University Medical Center Groningen (UMCG), University of Groningen, 9713 GZ Groningen, The Netherlands
| | - André P Wolff
- Pain Center, Department of Anaesthesiology, University Medical Center Groningen (UMCG), University of Groningen, 9713 GZ Groningen, The Netherlands
| | - Rita H R Schiphorst Preuper
- Department of Rehabilitation Medicine, University Medical Center Groningen (UMCG), University of Groningen, 9713 GZ Groningen, The Netherlands
| | - Alec G G A Malmberg
- Department of Obstetrics and Gynaecology, University Medical Center Groningen (UMCG), University of Groningen, 9713 GZ Groningen, The Netherlands
| | - Michiel F Reneman
- Department of Rehabilitation Medicine, University Medical Center Groningen (UMCG), University of Groningen, 9713 GZ Groningen, The Netherlands
| | - Hans Timmerman
- Pain Center, Department of Anaesthesiology, University Medical Center Groningen (UMCG), University of Groningen, 9713 GZ Groningen, The Netherlands
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12
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Ohashi Y, Uchida K, Fukushima K, Inoue G, Takaso M. Mechanisms of Peripheral and Central Sensitization in Osteoarthritis Pain. Cureus 2023; 15:e35331. [PMID: 36846635 PMCID: PMC9949992 DOI: 10.7759/cureus.35331] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/21/2023] [Indexed: 02/24/2023] Open
Abstract
Pain, the primary symptom of osteoarthritis (OA), reduces both the quality and quantity of life for patients. The pathophysiology of OA pain is complex and often difficult to explain solely by radiological structural changes. One reason for this discrepancy is pain sensitization (peripheral sensitization [PS] and central sensitization [CS]) in OA. Thus, an understanding of pain sensitization is important when considering treatment strategies and development for OA pain. In recent years, pro-inflammatory cytokines, nerve growth factors (NGFs), and serotonin have been identified as causative agents that induce peripheral and central sensitization and are becoming therapeutic targets for OA pain. However, the characteristics of the clinical manifestations of pain sensitization elicited by these molecules remain unclear, and it is not well understood who among OA patients should receive the therapeutic intervention. Thus, this review summarizes evidence on the pathophysiology of peripheral and central sensitization in OA pain and the clinical features and treatment options for this condition. While the majority of the literature supports the existence of pain sensitization in chronic OA pain, clinical identification and treatment of pain sensitization in OA are still in their infancy, and future studies with good methodological quality are needed.
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Affiliation(s)
- Yoshihisa Ohashi
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara, JPN
| | - Kentaro Uchida
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara, JPN
| | - Kensuke Fukushima
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara, JPN
| | - Gen Inoue
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara, JPN
| | - Masashi Takaso
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara, JPN
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From Low-Grade Inflammation in Osteoarthritis to Neuropsychiatric Sequelae: A Narrative Review. Int J Mol Sci 2022; 23:ijms232416031. [PMID: 36555670 PMCID: PMC9784931 DOI: 10.3390/ijms232416031] [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: 11/14/2022] [Revised: 12/08/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
Nowadays, osteoarthritis (OA), a common, multifactorial musculoskeletal disease, is considered to have a low-grade inflammatory pathogenetic component. Lately, neuropsychiatric sequelae of the disease have gained recognition. However, a link between the peripheral inflammatory process of OA and the development of neuropsychiatric pathology is not completely understood. In this review, we provide a narrative that explores the development of neuropsychiatric disease in the presence of chronic peripheral low-grade inflammation with a focus on its signaling to the brain. We describe the development of a pro-inflammatory environment in the OA-affected joint. We discuss inflammation-signaling pathways that link the affected joint to the central nervous system, mainly using primary sensory afferents and blood circulation via circumventricular organs and cerebral endothelium. The review describes molecular and cellular changes in the brain, recognized in the presence of chronic peripheral inflammation. In addition, changes in the volume of gray matter and alterations of connectivity important for the assessment of the efficacy of treatment in OA are discussed in the given review. Finally, the narrative considers the importance of the use of neuropsychiatric diagnostic tools for a disease with an inflammatory component in the clinical setting.
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Madi M, Hamzeh H, Abujaber S, Altubasi I. Cross cultural adaptation, validity, and reliability of Central Sensitization Inventory in Arabic language. Disabil Rehabil 2022; 44:8075-8083. [PMID: 34813384 DOI: 10.1080/09638288.2021.2006322] [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: 01/18/2023]
Abstract
PURPOSE The Central Sensitization Inventory (CSI) is a tool that aid in identifying symptoms associated with nociplastic pain. The aim of this study is to adapt CSI to Arabic language, and to examine its psychometric properties. METHODS Adaptation process followed recommended guidelines. Participants with self-reported chronic pain completed a web-based survey. The internal consistency was calculated. Test-retest reliability was examined by allowing 7-9 day gap between two rounds of measurements. Convergent validity was examined by measuring the correlation with Pain Catastrophizing Scale (PCS), EQ-VAS, and EQ-5D-3L. Discriminant validity was examined by testing four priori hypotheses. Factor analysis with principal components extraction was conducted. RESULTS CSI-Arabic (CSI-Ar) was successfully produced. Its internal consistency and test-retest reliability were excellent (Cronbach's α = 0.88 and ICC2,1=0.94). The standard error of measurement and minimal detectable change 95% were 3.45 and 9.57, respectively. CSI total score correlation with PCS, EQ-5D-3L, and EQ-VAS was moderate. The results lend support to the four hypothesis related to discriminant validity. Factor analysis revealed a four-factor structure of CSI-Ar. CONCLUSIONS CSI-Ar showed an internal consistency, test-retest reliability, and validity that are comparable to similar studies. The results support the use of CSI-Ar in assessing chronic pain in Arabic-speaking population.Implications for rehabilitationCentral sensitization (CS) mechanisms are thought to contribute to chronic pain.Identifying the presence of CS would personalize management.The Central Sensitization Inventory (CSI) is a valid and reliable tool to aid in identifying symptoms associated with CS.The Arabic version of the CSI is valid and reliable to use in Arabic speaking patients suffering from chronic pain.
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Affiliation(s)
- Mohammad Madi
- Department of Physiotherapy and Occupational therapy, Faculty of Applied Medical Sciences, The Hashemite University, Zarqa, Jordan
| | - Hayat Hamzeh
- Department of Physiotherapy, School of Rehabilitation Sciences, The University of Jordan, Amman, Jordan
| | - Sumayeh Abujaber
- Department of Physiotherapy, School of Rehabilitation Sciences, The University of Jordan, Amman, Jordan
| | - Ibrahim Altubasi
- Department of Physiotherapy, School of Rehabilitation Sciences, The University of Jordan, Amman, Jordan
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15
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Roby NU, Packham TL, MacDermid JC, Carlesso LC. Validity of the Central Sensitization Inventory (CSI) through Rasch analysis in patients with knee osteoarthritis. Clin Rheumatol 2022; 41:3159-3168. [PMID: 35754083 DOI: 10.1007/s10067-022-06248-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/01/2022] [Accepted: 06/14/2022] [Indexed: 11/03/2022]
Abstract
INTRODUCTION/OBJECTIVE Central sensitization (CS) is a known contributor to chronic pain in people with knee osteoarthritis (KOA) and is commonly measured by psychophysical testing or patient-reported methods such as the Central Sensitization Inventory (CSI). However, previous studies have shown a weak association between the two. We therefore sought to evaluate the validity of the CSI through Rasch analysis in patients with KOA. METHOD We performed a secondary analysis of a multicenter cohort study with patients with KOA consulting orthopedic surgeons. Rasch analysis was conducted considering person factors of age, sex, BMI, pain intensity, pain catastrophizing, and quantitative sensory test findings using pressure pain thresholds and temporal summation to assess how the CSI fits to the Rasch model (supporting validity). We used RUMM2030 software to model fit estimates, making adjustments as required to achieve model fit (P > 0.05). RESULTS Data from 293 patients were included (58.7% female, mean age 63.6 years, 49.1% obese) Initial evaluation with Rasch modelling indicated misfit. Eleven of 25 items on the CSI displayed disordered thresholds which were rescored by collapsing response categories until the thresholds demonstrated sequential progression. Reanalysis demonstrated persistent model misfit so a subtest was developed to address local dependency of 6 items. Thereafter, model fit was achieved (P = 0.071, indicating not differing from Rasch model) and acceptable unidimensionality (P = 0.068 with 95% CI 0.043-0.093). CONCLUSIONS The CSI was able to be fit to the Rasch model after rescoring while retaining all 25 items. The unidimensionality validates CS as measured by the CSI as a singular construct. Key Points • The Central Sensitization Inventory (CSI) was able to be fit to the Rasch model after rescoring while retaining all 25 items. • The unidimensionality of the CSI validates CS as a singular construct. • Our results suggest rescoring of the CSI for people with KOA, but it should be confirmed and replicated in larger samples prior to clinical use.
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Affiliation(s)
- Naym U Roby
- School of Rehabilitation Science, Faculty of Health Sciences, McMaster University, 1400 Main St. W, IAHS 441, Hamilton, ON, L8S 1C7, Canada
| | - Tara L Packham
- School of Rehabilitation Science, Faculty of Health Sciences, McMaster University, 1400 Main St. W, IAHS 441, Hamilton, ON, L8S 1C7, Canada
| | - Joy C MacDermid
- Physical Therapy and Surgery, Western University, London, ON, Canada
| | - Lisa C Carlesso
- School of Rehabilitation Science, Faculty of Health Sciences, McMaster University, 1400 Main St. W, IAHS 441, Hamilton, ON, L8S 1C7, Canada.
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16
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Ohashi Y, Uchida K, Fukushima K, Satoh M, Koyama T, Tsuchiya M, Saito H, Uchiyama K, Takahira N, Inoue G, Takaso M. Correlation between CD163 expression and resting pain in patients with hip osteoarthritis: Possible contribution of CD163+ monocytes/macrophages to pain pathogenesis. J Orthop Res 2022; 40:1365-1374. [PMID: 34370345 DOI: 10.1002/jor.25157] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 07/15/2021] [Accepted: 07/30/2021] [Indexed: 02/04/2023]
Abstract
Expression of CD163, a scavenger receptor specifically expressed by monocytes and macrophages, is elevated in the synovial tissue of patients with knee osteoarthritis (OA) compared with healthy controls. However, the association between CD163 expression in the synovium and pain in OA patients is unclear. We investigated the correlation between synovial CD163 expression and resting and active pain levels in patients with hip osteoarthritis (HOA). To investigate the possible contribution of CD163+ subsets to pain pathogenesis, we compared pain-related cytokine expression and M1/M2 macrophage marker expression in CD163+ and CD163- cells. We performed flow cytometric analysis to study the CD163+ cell population. We also examined pain-related cytokine expression and M1/M2 macrophage marker expression on CD163+ CD14high and CD163+ CD14low cells using cell sorting. Synovial CD163 expression significantly correlated with resting pain levels (p = 0.006; R = 0.321), but not active pain levels (p = 0.155; R = 0.169). Expression of the M1 macrophage marker CD80 was significantly higher in CD163+ than CD163- cells (p = 0.010), as was the expression of M2 macrophage markers CD206 and IL10 (CD206, p = 0.014; IL10, p = 0.005), and TNFA and IL1B (TNFA, p = 0.002; IL1B, p = 0.001). TNFA expression was significantly higher in CD163+ CD14low than CD163+ CD14high cells, while IL1B, IL10, and CD206 expression were comparable among these subsets. Our findings suggest that CD163 expression is associated with higher resting pain scores. As TNF-α plays a role in the pain process, CD163+ CD14low cells expressing TNFA may be a potent contributor to the pathogenesis of resting pain in HOA.
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Affiliation(s)
- Yoshihisa Ohashi
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan
| | - Kentaro Uchida
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan
| | - Kensuke Fukushima
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan
| | - Masashi Satoh
- Department of Immunology, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan
| | - Tomohisa Koyama
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan
| | - Maho Tsuchiya
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan
| | - Hiroki Saito
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan
| | - Katsufumi Uchiyama
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan
| | - Naonobu Takahira
- Department of Rehabilitation, Kitasato University School of Allied Health Sciences, Sagamihara City, Kanagawa, Japan
| | - Gen Inoue
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan
| | - Masashi Takaso
- Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan
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Abstract
Joint pain is the hallmark symptom of osteoarthritis (OA) and the main reason for patients to seek medical assistance. OA pain greatly contributes to functional limitations of joints and reduced quality of life. Although several pain-relieving medications are available for OA treatment, the current intervention strategy for OA pain cannot provide satisfactory pain relief, and the chronic use of the drugs for pain management is often associated with significant side effects and toxicities. These observations suggest that the mechanisms of OA-related pain remain undefined. The current review mainly focuses on the characteristics and mechanisms of OA pain. We evaluate pathways associated with OA pain, such as nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA), calcitonin gene-related peptide (CGRP), C–C motif chemokine ligands 2 (CCL2)/chemokine receptor 2 (CCR2) and tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), the NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, and the Wnt/β-catenin signaling pathway. In addition, animal models currently used for OA pain studies and emerging preclinical studies are discussed. Understanding the multifactorial components contributing to OA pain could provide novel insights into the development of more specific and effective drugs for OA pain management.
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Ohashi Y, Fukushima K, Uchida K, Koyama T, Tsuchiya M, Saito H, Uchiyama K, Takahira N, Inoue G, Takaso M. Adverse Effects of Higher Preoperative Pain at Rest, a Central Sensitization-Related Symptom, on Outcomes After Total Hip Arthroplasty in Patients with Osteoarthritis. J Pain Res 2021; 14:3345-3352. [PMID: 34707402 PMCID: PMC8542571 DOI: 10.2147/jpr.s322314] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 10/14/2021] [Indexed: 12/12/2022] Open
Abstract
Background In patients with hip osteoarthritis (OA), pain at rest, unlike pain on activity, is due to pain mechanisms that cannot be explained by nociceptive pain. However, it remains unclear whether central sensitization (CS) is one of the causes of exacerbated pain at rest in patients with hip OA. Therefore, we investigated the differences in causative factors and postoperative course of total hip arthroplasty (THA) between preoperative pain at rest and on activity in patients with hip OA. Methods In total, 120 patients (125 hips, 22 men and 98 women, aged 64.5±1.0 years) with hip OA were included. Preoperative pain at rest and on activity and CS were assessed using the visual analog scale (VAS) and CS Inventory (CSI), respectively. Postoperative assessments were evaluated using the Japanese Orthopedic Association Hip Disease Evaluation Questionnaire (JHEQ); pain, satisfaction, function, and mental scores were evaluated 6 and 12 months after THA. Results Multivariate regression analysis indicated the CSI score as affecting VAS for pain at rest (β=0.067, P=0.002) but not VAS for pain on activity (β=0.036, P=0.073). VAS for pain at rest had a weak negative correlation with satisfaction and pain scores at both 6 and 12 months after THA (satisfaction, r=-0.309, -0.278; pain, r=-0.202, -0.22). VAS for pain on activity was not correlated with JHEQ. The CSI score had a weak or moderate negative correlation with three scores other than the function score at both 6 and 12 months after THA (satisfaction, r=-0.266, -0.213; pain, r=-0.332, -0.203, mental, r=-0.427, -0.370). The function score was weakly correlated with the CSI score only 6 months after THA (function, r=-0.231, -0.190). Conclusion A higher level of preoperative pain at rest, a CS-related symptom, may affect postoperative pain persistence and dissatisfaction in patients with hip OA.
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Affiliation(s)
- Yoshihisa Ohashi
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, 252-0374, Japan
| | - Kensuke Fukushima
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, 252-0374, Japan
| | - Kentaro Uchida
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, 252-0374, Japan
| | - Tomohisa Koyama
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, 252-0374, Japan
| | - Maho Tsuchiya
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, 252-0374, Japan
| | - Hiroki Saito
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, 252-0374, Japan
| | - Katsufumi Uchiyama
- Department of Patient Safety and Healthcare Administration, Kitasato University School of Medicine, Sagamihara City, Kanagawa, 252-0374, Japan
| | - Naonobu Takahira
- Department of Rehabilitation, Kitasato University School of Allied Health Sciences, Sagamihara City, Kanagawa, 252-0374, Japan
| | - Gen Inoue
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, 252-0374, Japan
| | - Masashi Takaso
- Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, 252-0374, Japan
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NGF Expression and Elevation in Hip Osteoarthritis Patients with Pain and Central Sensitization. BIOMED RESEARCH INTERNATIONAL 2021; 2021:9212585. [PMID: 34589551 PMCID: PMC8476257 DOI: 10.1155/2021/9212585] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 09/02/2021] [Indexed: 11/17/2022]
Abstract
Osteoarthritis (OA) is a chronic degenerative musculoskeletal disease that causes articular cartilage degeneration and chronic pain. Research into OA animal models suggests that elevated NGF levels in the synovium contribute to pain and central sensitization (CS). However, it is unclear whether synovial NGF contributes to CS in patients with OA. We investigated the association between synovial NGF expression and clinical assessments of pain and CS in hip OA (hOA) patients. We also aimed to identify which cells in the synovium of hOA patients express NGF. Sixty-six patients who received total hip replacement and a diagnosis of hOA were enrolled. We measured NGF mRNA expression in synovial samples obtained from 50 patients using qPCR and analyzed the correlation of NGF expression with the CS inventory (CSI) score and Japanese Orthopaedic Association (JOA) score, a clinical scoring system for OA. To identify the synovial cells expressing NGF, we analyzed NGF mRNA expression in CD14+ and CD14- cells, which represent macrophage-rich and fibroblast-rich fractions, respectively, extracted from 8 patients. To further identify which macrophage subtypes express NGF, we examined NGF mRNA expression in CD14high and CD14low cells sorted from 8 patients. Synovial NGF mRNA expression was negatively correlated with JOA score but positively correlated with CSI score (JOA pain, r = −0.337, P = 0.017; CSI score, r = 0.358, P = 0.011). Significantly greater levels of NGF were observed in CD14- cells compared to CD14+ cells (P = 0.036) and in CD14high cells compared to CD14low cells (P = 0.008). In conclusion, synovial NGF expression is correlated with the degree of pain and CS in hOA patients. NGF is predominantly expressed in synovial fibroblasts. Further, CD14high synovial macrophages expressed higher levels of NGF. Our results may provide a novel NGF-targeted therapeutic strategy for hOA pain.
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