Background: This study investigates the psychological underpinnings of chronic pain conditions, specifically fibromyalgia, chronic headache, vulvodynia, and mixed condition (consisting of fibromyalgia in comorbidity with chronic headache and/or vulvodynia), with a focus on nociplastic pain mechanisms.Objective: The aim of the study is to better understand the psychological functioning of women with different chronic pain conditions to identify and discuss similarities and differences. In particular, we aim to explore any significant differences in the domain of traumatic experiences, in global defensive functioning, and in the domain of alexithymia among the evaluated groups. Further, the 4 groups with chronic pain will be compared with a healthy control group.Methods: A sample of 1006 Italian women diagnosed with chronic pain participated in the study, categorized into four clinical groups and a healthy control group. Measures were assessed using self-report measures, in particular: Traumatic Experiences Checklist, Defense Mechanism Rating Scales, and Toronto Alexithymia Scale.Results: There are significant differences among groups, with mixed conditions exhibiting the highest levels of traumatic experiences, particularly emotional neglect and physical threats. Fibromyalgia and mixed condition groups displayed greater reliance on neurotic defense mechanisms. Additionally, fibromyalgia and mixed condition participants exhibited higher levels of alexithymia, indicating difficulties in emotional processing.Conclusions: These findings underscore the complex interplay between psychological factors and nociplastic pain conditions, emphasizing the importance of personalized psychological interventions in managing nociplastic pain. The study highlights the need for multidisciplinary approaches to nociplastic pain treatment, considering the diverse psychological profiles of affected individuals.

Chronic pain exerts an enormous personal and economic burden worldwide. While clinical trials have confirmed the benefits of mindfulness-based interventions (MBIs) in chronic pain management, knowledge on the best type and dosage remains unknown. This study aims to compare the clinical effectiveness of different MBIs on chronic pain and to identify the optimal dosage of MBIs. The primary outcome was pain intensity and secondary outcomes were physical function and depression. We applied a random-effect pairwise meta-analysis to synthesize data, and network meta-analysis to compare effectiveness among different types and dosages of MBIs. The findings were further categorized according to the partially contextualized framework. A total of 68 studies with 5,339 participants were included. Mindfulness-based stress reduction demonstrated the most promising results for improving pain intensity (SMD -0.76, 95 % CI -1.06 to -0.46, Surface Under the Cumulative Ranking Area (SUCRA) 0.75) and depression (SMD -0.77, 95 % CI -0.98 to -0.56, SUCRA 0.86), supported by moderate and high certainty of evidence, respectively. On the other hand, mindfulness-oriented recovery enhancement emerged as the most effective for enhancing physical function (SMD -1.42, 95 % CI -2.28 to -0.57, SUCRA 0.96), albeit with low certainty of evidence. An 8-week course, conducted once per week, with sessions lasting between 90 and 120 min, appeared to be the optimal dosage for addressing pain intensity, physical function, and depression. Our findings contribute to the evidence supporting the use of MBIs in chronic pain management and informing the development of evidence-based guidelines and standardizing the course structures of MBIs. Systematic review registration: PROSPERO CRD42021293938.

Millions experience inadequately managed acute pain each year. Opioids are an important tool for managing pain; however, recent reductions in opioid prescriptions have exacerbated preexisting challenges in pain management. Moreover, patient expectations and desires for pain management may drive additional opioid use. There is an important need to characterize patient motivations for using opioids in order to develop promising interventions. The aim of this study was to develop the Decisions To use Opioids (DTO) measure.

We used an exploratory sequential mixed methods design to create items for the DTO measure. Qualitative data from patient interviews and focus groups informed the development of items for the DTO. We evaluated the content validity of candidate items with nine experts using the content validity index (CVI) and conceptual significance. Face validity was assessed via cognitive interviews with five emergency department (ED) participants who experienced acute pain.

We generated an initial pool of 52 items. Expert ratings provided evidence of content validity on 40 items, as indicated by an item CVI score of 0.83 or higher. Nine items with CVI scores of <0.83 were retained and revised due to the conceptual significance. The remaining three items were discarded.

This study provided evidence of content and face validity of the DTO measure for ED patients. Further psychometric evaluation is needed to gather data regarding the DTO's internal consistency, construct validity, and criterion validity.

Chronic pain is associated with many negative consequences for individuals and society. Given the burden it represents, many studies have focused on the risk factors involved, but very few have aimed to explain why some people live well with chronic pain, beyond the psychological realm. Thus, this study collected and analyzed different individual experiences to identify the pivotal conditions that help some individuals achieve quality of life despite chronic pain, with an emphasis on social considerations. We conducted a qualitative study using a narrative inquiry approach to unpack the participants' stories on these pivotal conditions. We carried out 25 individual interviews with persons who considered they had been living well with their pain for a minimum of 6 months. Data were analyzed using the inductive narrative method. Most participants were women (64%), White (88%), with a high level of education, and having low back or generalized pain (56%). Three main themes were identified: 1) a care partnership, 2) a nurturing environment, and 3) breaking free from previous life to move forward. These themes were then divided into 11 sub-themes, providing an in-depth understanding of the pivotal conditions needed to live well with chronic pain. The data collected suggest that to enable people to have a favorable evolution in the presence of chronic pain, a socio-ecological approach could be necessary to counteract painogenic environments. However, these results need to be validated and adapted to different populations. Perspective This study highlights the importance of a socio-ecological approach to living well with chronic pain, emphasizing that care partnerships, a nurturing environment and the ability to break with the past are essential to improve the quality of life of those affected.

This article aims to provide an illustrated account of layered stigmatisation processes and consequences for those who experience chronic pain and accompanying suicidality. Using constructivist grounded theory, I draw from 20 in-depth interviews conducted from 2022 to 2023 to explore how chronic pain and suicidality operate within people's social worlds. Findings demonstrate how layered stigmatising processes, occurring based on chronic pain and suicidality, operate consistently across multiple social arenas to create interactional troubles, which result in enduring negative social, emotional, and financial impacts. Three themes were constructed, including (1) self-stigma and the multiple roles of the family, (2) missed connections, and (3) anticipated stigma and workplace discrimination. Taken together, themes support the overarching category, 'interactional troubles'. Findings suggest a need for attunement to stigmatising processes' omnipresence and the depth of their consequences. Clinical interventions may benefit from emphasizing participants' social worlds and incorporating the complexity of navigating social arenas given layered stigmatisation. Moreover, policies that support those with chronic pain and mental illness could offset the long-term negative economic consequences of discrimination.

While the development of artificial intelligence (AI) technologies in medicine has been significant, their application to acute and chronic pain management has not been well characterized. This systematic review aims to provide an overview of the current state of AI in acute and chronic pain management.

This review was registered with PROSPERO (ID# CRD42022307017), the international registry for systematic reviews. The search strategy was prepared by a librarian and run in four electronic databases (Embase, Medline, Central, and Web of Science). Collected articles were screened by two reviewers. Included studies described the use of AI for acute and chronic pain management.

From the 17,601 records identified in the initial search, 197 were included in this review. Identified applications of AI were described for treatment planning as well as treatment delivery. Described uses include prediction of pain, forecasting of individualized responses to treatment, treatment regimen tailoring, image-guidance for procedural interventions and self-management tools. Multiple domains of AI were used including machine learning, computer vision, fuzzy logic, natural language processing and expert systems.

There is growing literature regarding applications of AI for pain management, and their clinical use holds potential for improving patient outcomes. However, multiple barriers to their clinical integration remain including lack validation of such applications in diverse patient populations, missing infrastructure to support these tools and limited provider understanding of AI.

This review characterizes current applications of AI for pain management and discusses barriers to their clinical integration. Our findings support continuing efforts directed towards establishing comprehensive systems that integrate AI throughout the patient care continuum.

There is a need for a systematic review on social functioning and peer relationships among adolescents with chronic pain (ACP) given the high prevalence of chronic pain in adolescence and integral role of peer relationships in adolescent development. This review aims to examine the methods used to evaluate social functioning, the types and extent of peer relationship difficulties, and pain characteristics and sociodemographic factors related to social functioning in ACP.

A systematic literature search of PubMed, PsycINFO, CINAHL, Web of Science, and Cochrane databases was performed. Included studies were written in English, presented original, quantitative, peer-reviewed research, had a primary focus on social functioning or peer relationships in ACP, and included study participants between the ages of 10 and 18 years. The review was registered in PROSPERO (No. CRD42022364870).

Twenty-eight articles were included in the review. All studies used self-, parent-, or peer-report questionnaires to evaluate social functioning. Most (89%) of the studies were cross-sectional. Findings suggest that ACP experience social difficulties frequently characterized by loneliness, social anxiety, withdrawal, and peer victimization. Studies examining the associations between social functioning and sociodemographic variables, pain location, and pain-related characteristics yielded mixed findings. Study quality was mixed, with 57.14% rated as "good."

Findings from this review emphasize the increased risk of reduced social connectedness and the complexity of underlying mechanisms associated with poorer social functioning among ACP. Additional research utilizing longitudinal methodologies is needed to understand potential moderators and directionality of associations between chronic pain and social functioning.

Pain is not experienced in isolation; it is affected by and affects other people. Interactions between parents and partners and people living with pain affect beliefs, emotions and behaviours, and pain progress and change. We searched systematically for longitudinal studies of associations between specific familial, dyadic, interpersonal factors and quantitative pain transitions. We coded studies for risk of bias. For the narrative synthesis, we grouped findings by dyads-parents and children, and people with pain and their partners (usually spouses), and then by the psychosocial mechanism/s. We described certainty of evidence for each pain transition and each mechanism. Patient and public contributors were involved throughout. Of 52 studies, 38 were of parents and children (27,814 dyads) and 14 of partners (4904 dyads). Three groups of predictive factors were identified for parent and child studies: parent mental health, parent cognitions, and parent behaviours. Parental anxiety (but not depression) predicted children's onset of pain and worsening; the evidence was of moderate certainty and almost exclusively involved mothers. Evidence that some parental behaviours, such as protective behaviours, were associated with worse child pain was of very low certainty. The evidence for partners was of poor quality, precluding synthesis. The review highlights that most interpersonal pain research fails to capture the complex dynamics of longstanding relationships and highlights the difficulty of doing so using simple models.

Patient satisfaction is important in pain management. Satisfaction with prescribed pain relievers and continued use of these drugs may be affected by a patient's understanding of their efficacy and safety. We investigated the association between patients' satisfaction and understanding of their prescribed medication for three oral pain relievers (lasmiditan, mirogabalin, and tramadol) that recently became available in Japan.

This questionnaire-based, cross-sectional study included adult patients taking these oral pain relievers after April 2023. The primary endpoint was overall satisfaction (five-point rating) and the secondary endpoint was overall understanding (five-point rating) of the oral pain relievers.

In total, 328 patients (lasmiditan, 36.9%; mirogabalin, 55.5%, tramadol, 8.8%; four patients had been prescribed more than one medication) were included, and 71.6% of patients reported high satisfaction (score 4, 5) with their oral pain relievers (lasmiditan, 62.0%; mirogabalin, 76.1%; tramadol, 85.2%). The proportion of patients in the total population who reported a high understanding (score 4, 5) of their oral pain relievers was 68.0% (lasmiditan, 77.7%; mirogabalin, 63.3%; tramadol, 55.6%). In the total population and the lasmiditan and mirogabalin subgroups, the patient satisfaction level was significantly associated with scores on medication understanding (Cochran-Armitage test, p < 0.0001 for all). Discontinuation rates were higher in patients who were unsatisfied with their treatment than those who were satisfied (38.7% and 9.8%, respectively).

This study showed that a higher level of understanding of oral pain relievers is associated with higher satisfaction, which may be associated with lower discontinuation rates.

UMIN000052629.

Fibromyalgia is called a pathology of misconnection at the neurophysiological, psychological, and social levels, and is characterised by widespread musculoskeletal pain, which is accompanied by a series of symptoms, such as chronic fatigue, depression, anxiety, body perception disturbances, and cognitive deficits. In this article, I argue that interventions that in various ways enhance interpersonal neural synchronisation (INS) may bring long-term benefits to people with fibromyalgia (PwF). In the first part, I briefly introduce studies on INS in the general population. In the second part, I hypothesise that interpersonal synchrony may contribute to symptom reduction for individuals with fibromyalgia, in the sense that repeated experience of being in sync with others may play a role in restoring both the brain-body and self-others connection in this population and consequently result in simultaneous lasting improvement of wellbeing. In the final part, I discuss potential future research directions.

Neck pain is a prevalent global health concern often accompanied by musculoskeletal symptoms. This randomized controlled trial attempted to contrast the impacts of non-thrust Maitland mobilization and Autogenic inhibition muscle energy technique on chronic mechanical neck pain associated with cervico-thoracic junction hypo-mobility.

Sixty participants (24 males and 36 females, aged 18-45 years) were allocated randomly into three equally sized groups (A, B, C). Group A: Maitland mobilization plus conventional treatment, Group B: Autogenic Muscle energy technique plus conventional treatment, while; Group C solely received conventional treatment. Treatment was administered for four weeks, three times a week. Outcome measures: neck pain (The primary outcome measure) assessed by Visual Analog Scale (VAS), disability evaluated through Neck Disability Index (NDI), active range of motion (AROM), and joint position error (JPE) as an indicator of cervical proprioception. All measures were assessed both at baseline and after four weeks of intervention.

Results showed significant improvements in VAS, NDI, and increased ROM across all groups post-treatment (p < 0.001). While Groups A and B demonstrated superior outcomes compared to Group C, differences between Groups A and B were not statistically significant (p > 0.05). For VAS and NDI, Cohen-d between Groups A and B was 0.31 and 0.31, and for ROM, Cohen-d was 0.37, 0.16, 0.07, 0.29, 0.36, and 0.53 for flexion, extension, right rotation, left rotation, right bending, and left bending, respectively. Furthermore, all groups experienced a significant decrease in JPE, with Groups A and B showing greater improvement than Group C (p < 0.01). Group B exhibited significantly greater improvement in reducing JPE related to specific motions compared to Group A (p < 0.05).

Cervico-thoracic junction mobilization and the Autogenic muscle energy technique offer enhanced management for mechanical neck pain by improving pain, function, ROM, and cervical proprioception.

Mental defeat is considered a potential risk factor for suicidal thoughts and behaviours in chronic pain. This study evaluated the role of mental defeat in predicting future suicide risk and examined whether depression influences this relationship.

A total of 340 participants with chronic pain completed questionnaires at two time points, 12 months apart. Data collected included sociodemographic and pain characteristics, mental defeat, psychosocial risk factors including depression and health-related variables. Weighted univariate and multivariable analyses assessed the link between mental defeat and suicide risk, with a moderation analysis testing the role of depression.

Higher levels of mental defeat and depression were linked to increased suicide risk at 12 months. Depression significantly amplified the effect of mental defeat on suicide risk, particularly in individuals with higher depression levels (B = 0.06, SE = 0.01, t = 6.21, p < 0.001) compared with moderate (B = 0.05, SE = 0.01, t = 5.20, p < 0.001) or low levels of depression (B = 0.04, SE = 0.01, t = 2.83, p = 0.004), indicating a dose-response relationship.

Mental defeat is a significant risk factor for suicide in chronic pain, with depression intensifying this risk. Addressing both mental defeat and depression simultaneously in treatment may help reduce suicide risk in these patients.

This study strengthens the evidence linking mental defeat with heightened suicide risk in chronic pain. By providing prospective data, it clarifies the temporality of this relationship. Given that suicide risk doubles in chronic pain patients, whereby comorbid depression is common, these findings have crucial clinical implications. Both mental defeat and depression are modifiable. Addressing them together in treatment may help reduce suicide risk in this population.

Background/Objectives: Pain science education accommodating low health literacy is needed for people with chronic pain. The purpose of this study was to translate PNE4Kids, contextually adapt it into PNE4Adults, and test the feasibility of the newly developed pain science education program (PNE4Adults) for adult patients with chronic musculoskeletal pain in the municipality. Methods: A three-step approach was used to (1) translate PNE4Kids into Danish, (2) adapt to age and context (PNE4Adults), and (3) test the feasibility. (1) Translation was performed by a native Dane fluent in Dutch. (2) Two think-aloud group sessions were held, with therapists and end users. (3) Feasibility was tested amongst twenty adult patients with chronic musculoskeletal pain consecutively referred for rehabilitation in the municipality. The a priori success criteria were determined to be 70% acceptability and 70% understandability. Prior to inclusion of the first patient, the study was pre-registered on clinicaltrial.gov [NCT05140031]. Results: Translation was successfully performed. Both the therapist and end users found the program easy to grasp, the simplicity and interactive nature of the program ingenious, and the program to be well suited to an adult population. All patients (100%), across health literacy levels, found PNE4Adults comprehensible and acceptable. Conclusions: The aims were successfully met. Progression to a full trial is warranted and is underway.

Suffering from chronic pain (CP) and coping with parenthood can be challenging for parental mental health. Pain can hinder the ability to deal with demands related to parenthood, which can negatively affect their psychological well-being because of unmet caregiving expectations.

Considering the limited amount of research regarding the mental health of parents with CP, the study's main aim was to test a predictive model based on previous scientific literature, using structural equation analysis, in which parental competence and parental guilt partially mediate the relationship between parental stress and depression. To examine the moderating role of CP, the model was tested on a group of parents with CP and a control group of parents without CP. The study included 380 parents from all over Spain, of which 200 formed the group with CP and 180 participants formed the control group. A cross-sectional design was used to collect data through self-report measures.

Higher levels of stress, guilt, and depression were observed in parents with CP. Based on the results, both groups of parents showed a good fit with the predictive model; parental stress was a good predictor of symptoms of depression both in parents with and without CP, parental competence mediated the relationship between parental stress and depression, being the relationship between competence and depression partially mediated by parental guilt.

This study is the first to quantitatively examine parental competence and guilt in parents with CP, and to analyze their role as mediators between parental stress and depression in both CP and healthy parents. The results confirm previous qualitative findings and extend them to parents with CP, showing that the tested model aligns with the main theories on stress, self-efficacy, and depression, as well as existing literature on CP. These results suggest the relevance of addressing parental stress levels for reducing and preventing depressive symptoms in parents with CP and the importance of working on guilt reduction and enhancing competence in order to improve the emotional well-being of parents. The need to take into account the mental health of parents with CP to improve their quality of life is discussed.

The limitations of pharmacological treatments for chronic pain have become increasingly evident: dependency, side effects, resistance, and diminishing efficacy. The urgent need for innovative solutions has become a compelling focus for improving patient outcomes. Innovative non-pharmacological approaches, such as sleep management, as a strategy to reduce opioid consumption and pain control are needed. The aim was to evaluate the impact of a Sleep and Circadian Intervention Program (SCIP) in the control of chronic musculoskeletal pain (CMP). This was a randomized clinical trial (NCT03646084), in which 49 CMP patients were assigned to SCIP (n = 15, mean age 51 years and 40% women) or non-SCIP groups (n = 26, 53 years and 61.5% women). Outcomes were evaluated after 6 months through self-reported questionnaires (pain intensity, physical function, depression/anxiety, and quality of life (QoL)). The SCIP group was assessed by polysomnography and specific questionnaires and was treated for diagnosed sleep disorders according to clinical guidelines. This population showed a moderate pain intensity at baseline, important deterioration of QoL and pathological anxiety/fear related to pain. Fifty percent of them presented restless leg syndrome, 60% moderate/severe insomnia, and 62.5% sleep apnea. During the follow-up, the SCIP group presented a greater reduction in the abnormal risk group for anxiety (from 73.3% to 46.7%) and depression (from 53.3% to 33.3%) on the Hospital Anxiety and Depression Scale compared to the non-SCIP group (from 40% to 29.2% and 33.3% to 29.2%, respectively). Also, a positive significant effect on anxiety/fear related to pain was found in the Pain Anxiety Symptoms Scale multivariable model, with an important improvement in symptoms. The application of SCIP in CMP patients improved anxiety and controlled associated sleep disorders, highlighting the impact on insomnia. Larger studies are needed for better understanding of the sleep intervention in CMP control.

Chronic pain (CP) is a public health problem worldwide.

To update the prevalence of CP and compare the clinical and social characteristics of people with CP with those with non-chronic continuous pain and a group without pain.

An observational cross-sectional study was carried out in a representative sample of 7058 adults from the Spanish population. Sociodemographic data, the presence of CP and non-chronic continuous pain, characteristics of pain, limitations on activities of daily living (ADL), the presence and level of anxiety and depression (HADS), quality of life (SF-12v2) and social support (DUKE) were collected. Descriptive and bivariate analyses were performed.

The prevalence of CP was 25.9% (95% CI;24.8-26.9) and that of non-chronic continuous pain was 7.7% (95% CI;7.1-8.3). Women presented a higher prevalence of both CP (30.5% vs. 21.3%) and non-chronic continuous pain (8.8% vs. 6.6%). CP was more common in the group between 55 and 75 years old (30.6%, 95% CI = 28.6-32.6%), non-chronic continuous pain affected most the population between 18 and 34 years old (11.2%, 95% CI = 9.6-12.7%). The median duration of CP was 4 years. The lumbar was the most frequent pain site (58.1%), and 27.1% did not know the cause. A greater frequency of limitations on ADL, more anxiety and depression, and worse quality of life were shown among the subjects with CP.

CP affects one in four Spanish people and impairs the mental, physical and social health. Differences exist by sex and age in its frequency. Identifying subjects with non-chronic continuous pain is fundamental to prevent their pain from becoming chronic.

Indicating the main aspects where this work adds significantly to existing knowledge in the field, and if appropriate to clinical practice. Due to its high prevalence and impact on quality of life, chronic pain has become one of the main health problems nowadays. Attention must be paid to it both from a clinical and social perspective, trying to raise awareness among the population of its possible causes and consequences. In routine clinical practice, greater consideration is given to groups of people with a higher prevalence of chronic pain, such as women and people with middle age, and with no chronic pain to prevent the appearance of chronic pain.

There is a lack of integrated treatment for chronic pain and opioid use disorder (OUD). Yoga and physical therapy (PT) may improve pain and physical function of people living with (PLW) chronic low back pain (CLBP) and may also reduce opioid craving and use, but PLW with OUD face barriers to accessing these interventions. We hypothesize that compared to treatment as usual (TAU), providing yoga and PT onsite at opioid treatment programs (OTPs) will be effective at improving pain, opioid use, and quality of life among people with CLBP and OUD, and will be cost-effective.

In this hybrid type-1 effectiveness-implementation study, we will randomly assign 345 PLW CLBP and OUD from OTPs in the Bronx, NY, to 12 weeks of onsite yoga, onsite PT, or TAU. Primary outcomes are pain intensity, opioid use, and cost-effectiveness. Secondary outcomes include physical function and overall well-being.

This trial tests an innovative, patient-centered approach to combined management for pain and OUD in real-world settings. We rigorously examine the efficacy of yoga and PT onsite at OTPs as nonpharmacologic, cost-effective treatments among people with CLBP and OUD who face barriers to integrated care.

Chronic postsurgical pain (CPSP) has a great impact on quality of life and socioeconomic status. The mechanisms behind CPSP remain poorly understood, however type of surgical intervention seems to play a role. Gastrointestinal surgeries are common procedures, yet research in CPSP following gastrointestinal surgery is limited. The objective of this scoping review was to map the current literature on CPSP following gastrointestinal surgery, identifying how CPSP have been investigated, and which evidence gaps exist.

This scoping review followed a pre-published protocol and PRISMA-ScR guidelines. A search was carried out in Medline, Embase, CINAHL, Cochrane Central, Clinicaltrials.Gov, and Google Scholar. Eligible studies were original studies involving adults, undergoing gastrointestinal surgery, who had a pain assessment ≥30 days postoperatively. A two-phase screening process and data charting were done by two independent reviewers.

A total of 53 studies were included, published between 2001 and 2024, predominantly across Europe and Asia. The range of CPSP prevalence reported was 3.3%-46.1%. Only half the studies clearly defined CPSP, and the timing and manner of pain assessment varied considerably. Twenty-seven studies assessed risk factors for developing CPSP: preoperative pain and acute postoperative pain were consistently significant.

There was a wide consensus on CPSPs' negative impact on quality of life. CPSP following gastrointestinal surgery is prevalent and significantly impacts quality of life. Standardized definitions and methodologies to improve the comparability and reliability of the findings across studies are needed. Future research should focus on CPSP following specific surgical procedures to develop tailored prevention and treatment strategies.

Chronic pain is a serious and prevalent condition that can affect many facets of life. However, uncertainty remains regarding the strength of the association between chronic pain and death and whether the association is causal. We investigate the pain-mortality relationship using data from 19,971 participants aged 51+ years in the 1998 wave of the U.S. Health and Retirement Study. Propensity score matching and inverse probability weighting are combined with Cox proportional hazards models to investigate whether exposure to chronic pain (moderate or severe) has a causal effect on mortality over a 20-year follow-up period. Hazard ratios (HRs) with 95% confidence intervals (CIs) are reported. Before adjusting for confounding, we find a strong association between chronic pain and mortality (HR: 1.32, 95% CI: 1.26-1.38). After adjusting for confounding by sociodemographic and health variables using a range of propensity score methods, the estimated increase in mortality hazard caused by pain is more modest (5%-9%) and the results are often also compatible with no causal effect (95% CIs for HRs narrowly contain 1.0). This attenuation highlights the role of confounders of the pain-mortality relationship as potentially modifiable upstream risk factors for mortality. Posing the depressive symptoms variable as a mediator rather than a confounder of the pain-mortality relationship resulted in stronger evidence of a modest causal effect of pain on mortality (eg, HR: 1.08, 95% CI: 1.01-1.15). Future work is required to model exposure-confounder feedback loops and investigate the potentially cumulative causal effect of chronic pain at multiple time points on mortality.

Introduction Opioid-induced constipation (OIC) is the most common side effect of opioids. Weak opioids are often prescribed for non-cancer chronic pain in Japan; however, data on laxative use are scarce. We evaluated the real-world prescription patterns of laxatives for OIC in patients administered weak opioids for non-cancer pain in Japan. Methods In this retrospective cohort study, we extracted data from a Japanese health insurance claims database for patients with chronic non-cancer pain (lower back pain, joint pain, and neuropathic pain) who were continuously prescribed weak opioids for ≥1 month after initiating weak opioids between 2017 and 2022. Results Of 425,556 patients prescribed weak opioids, 42,514 patients (mean age: 50.1 years) were included. Most were prescribed ≤150 mg tramadol equivalent/day, and 21,405 (50.3%) were on weak opioids for lower back pain. The proportion of laxatives prescribed on the first day of weak opioid prescription was 6.7%; the cumulative prescription rate during the 12‑week follow-up was 13.6%. The most common laxatives during the first week were magnesium oxide (2,320 (66.6%)), sennoside (484 (13.9%)), and naldemedine (301 (8.6%)); at 12 weeks, these proportions were 55.2%, 13.1%, and 13.8%, respectively.​ The amount of weak opioids prescribed to patients without laxatives was lower than the standard dosage and was also lower than the amount prescribed to patients with laxatives. Conclusions This study showed that the actual prescription patterns of laxatives after initiating weak opioids in patients with chronic non-cancer pain were variable, depending on the duration after initiating weak opioids. The association between laxative use and weak opioid dosage indicates that OIC management may have a potential impact on pain management.

We introduce two Korean-named yet transcultural feelings, jeong and haan, to fill gaps in neuroscientific understanding of mammalian bondedness, loss, and aggression. Jeong is a visceral sense of connectedness to a person, place, or thing that may arise after proximity, yet does not require intimacy. The brain opioid theory of social attachment (BOTSA) supports the idea that jeong involves increased activity of enkephalins and beta-endorphins. We propose that withdrawal of jeong-related neuropeptides leads to original haan, a sense of "missingness" that is too subtle to be grossly dysphoric. Through narrative, cognitive appraisals, or moral assignments, however, original haan may transform into the feeling of constructed haan-resentment, bitterness, grievance, sorrow, or suppressed anger. In males, the transformation may be driven by arginine vasopressin, an ancient fight-or-flight neurohormone. Constructed haan may also be driven by vasopressin in females, though data is more sparse, and in both sexes it may depend on situational or societal context. Endogenous opioids inhibit vasopressin, so that when jeong diminishes, vasopressin release may become disinhibited. This relationship implies a companion to the BOTSA, which we articulate as the brain opioid and vasopressin theory of original and constructed haan (BOVTOCH). To illustrate, we reflect on borderline personality disorder, and Vincent van Gogh's self-severing of his ear while living and working with Paul Gauguin, and fearing abandonment by him; yet to understand Van Gogh more completely we also present the brain opioid theory of stable euphoric creativity (BOTSEC), to model the subjective "highs" associated with creative flow states. Together these brain opioid theories may help to explain how feelings related to social bondedness can influence a range of phenomena. For example, opioid drug dependence may be, at least partly, a maladaptive response to feelings of isolation or disconnectedness; the health protective effects of social bonds could be related to tonic exposure to endogenous opioids and their anti-inflammatory properties; endogenous opioid-based social relational enhancement may contribute to placebo responding. Finally we conclude by pointing out the possibility of virtuous cycles of social connectedness and creativity, when feelings of bondedness and euphoric flow reinforce one another through endogenous opioid elevation.

Cardiovascular diseases are a leading cause of morbidity and mortality worldwide. Clinically, various techniques are used to diagnose coronary artery diseases. Coronary angiography is considered the gold standard for the diagnosis of coronary artery disease. The aim of this study is to determine the effect of cold spray applied before local anesthesia on pain and anxiety during coronary angiography procedures.

The study was designed as a randomized controlled trial.

The study was conducted in the angiography unit of a training and research hospital between January and March 2023. Data collection tools included a patient information form, Visual Analog Scale, and State-Trait Anxiety Inventory.

When the total mean scores of the Visual Analog Scale of the individuals in the intervention and control groups were examined, a statistically significant difference was found between the mean scores of the patients in the intervention group and the control group (P < .05). A significant difference was found between the individuals in the intervention and control groups in terms of the total scores of the state anxiety scale after cold spray (P < .001), with the mean scores of the control group higher than the intervention group.

The application of cold spray before local anesthesia in coronary angiography significantly reduced pain and anxiety levels.

Pain and depression are linked to higher mortality risk and lower subjective survival probabilities (SSPs). We examine if SSPs for individuals with pain and depression match their actual lifespans.

Using data on 12,745 Health and Retirement Study respondents aged 57-89 in 2000 with follow-up through 2018, we assessed whether respondents' SSPs were "correct," "underestimated," or "overestimated" relative to their lifespans. Adjusted multinomial logistic regressions predicted SSP accuracy based on pain interference, depression, and their interaction.

Severe or interfering pain (i.e., high impact pain) was associated with a 25% higher risk of underestimating SSPs (RRR = 1.25, p = .04), and depression increased the risk by 49% (RRR = 1.49, p < .001). High impact pain and depression also corresponded with lower average SSPs and higher mortality risk.

High impact pain and depression increase the risk of underestimating longevity. Future research should explore the impact on health and financial decisions in older adults.

Chronic pain (CP) is a complex and debilitating condition that significantly impairs quality of life and imposes a high burden on healthcare systems. This study aims to evaluate the impact of telemedicine on chronic pain management in cancer survivors with complex CP. Our multicenter retrospective investigation of cancer survivors with complex CP included 100 patients (median age 65 years, 62% female). Pain, disability, and self-perceived health status were assessed using the Numeric Rating Scale (NRS), Brief Pain Inventory (BPI), Oswestry Disability Index (ODI), and the EuroQolfive-dimension five-level (EQ-5D-5L) questionnaire. The most common diagnoses were neuropathic pain (54%) and complex chronic pain (32%). Significant clinical improvements were observed after six months of telemedicine intervention (all p < 0.001). NRS scores improved by more than four points in 77% of patients, BPI Worst Pain Scores decreased by four points in 52% and by five points in 28% of patients. All patients' disability levels improved from severe (median ODI score of 52) to moderate (median ODI score of 30). Self-perceived health status improved from 40 to 60 on the EQ-5D-5L scale. Telemedicine interventions significantly reduced pain intensity, decreased disability levels, and enhanced quality of life in chronic pain patients. These findings underscore the transformative potential of telemedicine in chronic pain management and support its broader integration into medical practice.

The objective of this cross-sectional survey-based study was to assess factors associated with patient satisfaction with physical therapy (PT) services received at a Federally Qualified Health Center (FQHC) in the United States (US) located near the US-Mexico border.

Patients > 18 years of age, English or Spanish speakers, referred to PT were invited to complete an online survey. Factors that may influence PT satisfaction were examined for patients who attended PT. Variables associated with PT satisfaction from bivariate analyses (p < .15) were included in three separate ordinal logistic regression models.

Patients (N = 231) who reported more confidence that PT could help relieve their pain were more likely to have higher levels of satisfaction with PT communication, treatment, and outcomes than those who reported low confidence (p < .05). Patients who reported having more support from family and friends were more likely to have higher levels of satisfaction with PT communication and treatment than those with less support (p < .01). Patients with occasional or frequent pain after ending PT treatment were more likely to have lower satisfaction with PT outcomes than those reporting no pain (p < .05).

Findings suggest that addressing confidence in PT and promoting health support from family and friends may be important for satisfaction with PT. Additionally, PTs may consider addressing gaps between expected and achieved outcomes to improve PT satisfaction.

Emerging literature has demonstrated deficits in interoception (i.e., the perception of physical sensations from inside the body) in individuals with chronic pain conditions. Mind-body therapies (MBTs) are purported to improve chronic pain in part through improving or restoring interoceptive abilities. The present systematic review and meta-analysis aimed to examine changes in interoception in MBTs for chronic pain conditions.

A systematic search of PubMed, PsycINFO, Scopus, CINAHL, and ProQuest Dissertation and Theses was conducted from database inception to February 2023. English language intervention studies evaluating the effect of MBTs on interoception in adults with chronic pain conditions were examined. Changes in pain (severity and interference) following treatment were examined as secondary outcomes.

A total of 11 studies (10 unique samples) were identified. Meta-analytic results reveal significant improvements in total interoceptive awareness (Becker's d = 1.168, p < .01) as well as improvements in seven of eight subdomains of interoceptive awareness (ds = 0.28 to 0.81). MBTs were also associated with reductions in both pain intensity (d = -1.46, p = .01) and pain interference (d = -1.07, p < .001).

Preliminary research suggests that MBTs demonstrate improvements in interoceptive awareness and reduce pain in adults with chronic pain. Literature on changes in other domains of interoception, such as interoceptive accuracy, following MBTs is severely lacking. Although more rigorous studies are needed to corroborate results, the present findings lay an important foundation for future research to examine interoception as a possible underlying mechanism of MBTs to improve pain outcomes.

Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Under -treatment of pain continues to be a major health care problem in Ethiopia. Although it has this problem, it receives limited research attention. This systematic review and meta-analysis will provide valuable insights of prevalence and its factors of healthcare providers' pain management practice in Ethiopia.

This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Universal online databases such as PubMed, Cochrane, Google, Google Scholar, SCOPUS, Web of Science and Global Health were used to search for articles. Microsoft Excel for data extraction and STATA17 for data analysis were used. DerSimonian and Laird random-effects model was used to pool the odds ratios across studies and compute the overall pooled prevalence and its predictors. Egger's test with funnel plot symmetry and Cochrane's Q test was used to assess publication bias and heterogeneity respectively.

The overall pooled prevalence of health care providers' pain management practice was 39.6% (95% CI: 34.8, 44.5); I2 = 97.0%; P<0.001). Availability of pain management protocol (AOR = 5.1, 95%CI: 3.6, 6.7), Accessibility of analgesia (AOR = 4.5, 95%CI: 1.96, 7.0), higher educational level (AOR = 3.3, 95%CI: 2.5, 4.1), being female (AOR = 1.2, 95% CI: 1.6, 3.1), took training (AOR = 2.7, 95% CI: 1.8, 3.6), decreased work load (AOR = 4.9, 95% CI: -1.9, 11.7), increased work experience (AOR = 3.9, 95% CI: 2.9, 5.1), Being midwifery profession (AOR = 2.5,95% CI: 1.6, 3.4), having good attitude (AOR = 3.9,95%CI: 2.5, 5.4) and being knowledgeable (AOR = 4.2, 95%CI: 2.8, 5.6) of health care providers towards pain management practice were significantly associated in Ethiopia.

The overall prevalence of pain management practice among healthcare providers in Ethiopia is low compared with a national target of pain free hospital initiatives in Ethiopia. It needs a call to build health care providers' ongoing education, training, professional development and manageable workload.

Physiotherapy is effective to reduce pain and improve the quality of life of people living with chronic pain. To offer high-quality physiotherapy services, these services must be patient-centred and respond to patients' needs. However, few studies seem to target patients' perceived needs, whereas more studies tend to focus on needs assessed by healthcare experts, which are not always in line with patients' perceived needs. In addition, people living with chronic pain are often faced with several health inequities and may have varied perceived needs depending on their personal conditions. To offer services that truly meet patients' needs, it is therefore crucial to understand these needs. This scoping review aims to identify and map the perceived needs of people living with chronic pain towards physiotherapy services.

To conduct this review, we followed the six stages framework proposed by Arksey and O'Malley. We searched four databases (Medline, Embase, CINHAL and APA PsycINFO) as well as the grey literature. We included all studies describing the needs, demands, preferences or expectations of adults living with chronic pain towards physiotherapy. We then performed an inductive thematic analysis of the results and discussion sections of these studies to identify the perceived needs. Once those needs were identified, we mapped them into the seven dimensions of the patient-centred healthcare delivery framework.

Our review included 96 studies. Various perceived needs were identified through the thematic analysis, such as the needs for an empathetic relationship; for a clear, adapted and supervised exercise program; and for personalized treatment. Our mapping into the patient-centred healthcare delivery framework showed that most studies reported needs associated with the dimensions of interpersonal care, individualized healthcare and professional care. Needs associated with the other dimensions of the framework (access; coordination and continuity; services and facilities; data and information) were less frequently mentioned.

The results of this review have enabled us to identify and better understand multiple needs perceived by people living with chronic pain regarding physiotherapy services. The perceived needs identified through this scoping review were mapped within the seven dimensions of the Patient-centred healthcare delivery framework.

Hereditary multiple exostoses (HME) is a genetic disorder defined by the formation of benign bone tumors known as exostoses, which can lead to chronic pain and functional impairment. This case report details a 57-year-old man with a long-standing history of severe diffuse bone pain attributed to HME. Despite various treatments, his pain remained poorly controlled until an intrathecal pump with fentanyl was implanted. This intervention significantly improved his pain management and overall quality of life. The manuscript explores clinical presentation, diagnostic approach, and treatment outcomes, highlighting the challenges and benefits of intrathecal drug delivery systems in managing refractory pain associated with HME.

Approximately one in three older adults (aged 65 years and over) experience pain, negatively impacting their quality of life. Opioid analgesics are commonly prescribed to manage pain; however, balancing the benefits and harms of these high-risk analgesics can be challenging for both healthcare professionals and patients. This is particularly true for older adults, as factors such as polypharmacy, age-related physiological changes and cognitive decline may impact upon opioid safety and efficacy. Deprescribing is the patient-centred process of reducing or discontinuing a medication that is no longer appropriate, or where the risks of continuation are deemed to outweigh the anticipated benefits. Opioid deprescribing has been proposed as a mechanism to reduce individual and societal opioid-related harm; however, to date, research has predominantly focused on the general adult population, rather than older adults. This current opinion aims to summarise the existing opioid deprescribing literature, discussing its applicability for older adults. Drawing on a non-systematic review of the literature, it identifies unique challenges and considerations for this population, highlights international initiatives to enhance opioid deprescribing in clinical practice and proposes future directions to advance the field.

This parallel, 2-arm, blinded, randomized controlled superiority trial examined whether, when added to usual care, active-electroencephalography neurofeedback (EEG NFB) was safe and more effective than sham control-EEG NFB for chronic pain. In total, 116 participants with chronic pain were randomly assigned (1:1) to usual care plus ≥32 sessions of active-EEG NFB upregulating relative alpha power over C4 or usual care plus ≥32 sessions of sham control-EEG NFB. Per-protocol analyses revealed no significant between-group differences in the primary outcome, Brief Pain Inventory average pain (mean difference [95% confidence interval]: -.04 [-.39 to .31], P = .90), or any secondary outcomes. However, 44% of participants in the active-EEG NFB group and 45% in the control-EEG NFB group reported at least a moderate (≥30%), clinically important improvement in Brief Pain Inventory average pain. The number of treatment-emergent adverse events were similar in both groups (P = .83), and none were serious. Post hoc analyses revealed similar upregulated relative alpha power in both groups during training, with concordant positive rewards delivered to the active-EEG group 100% of the time and the control-EEG group ∼25% of the time, suggesting a partially active sham intervention. When added to usual care, the active-EEG NFB intervention used in this study was not superior to the sham control-EEG NFB intervention. However, a large proportion of participants in both groups reported a clinically important reduction in pain intensity. A partially active sham intervention may have obscured between-group differences. The intervention was free of important side effects, with no safety concerns identified. PERSPECTIVE: This study is the first attempt at an appropriately blinded, randomized, sham-controlled trial of alpha EEG NFB for the treatment of chronic pain. The findings may interest people living with chronic pain, clinicians involved in chronic pain management, and may inform the design of future EEG NFB trials. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000667819.

N-acetylcysteine (NAC) has established use as an antidote for acetaminophen overdose and treatment for pulmonary conditions and nephropathy. It plays a role in regulating oxidative stress and interacting with various cytokines including IL-1β, TNFα, IL-8, IL-6, IL-10, and NF-κB p65. The overexpression of reactive oxygen species (ROS) is believed to contribute to chronic pain states by inducing inflammation and accelerating disease progression, favoring pain persistence in neuropathic and musculoskeletal pain conditions. Through a comprehensive review, we aim to explore the mechanisms and inflammatory pathways through which NAC may manage neuropathic and musculoskeletal pain. Evidence suggests NAC can attenuate neuropathic and musculoskeletal pain through mechanisms such as inhibiting matrix metalloproteinases (MMPs), reducing reactive oxygen species (ROS), and enhancing glutamate transport. Additionally, NAC may synergize with opioids and other pain medications, potentially reducing opioid consumption and enhancing overall pain management. Further research is needed to fully elucidate its therapeutic potential and optimize its use in pain management. As an adjuvant therapy, NAC shows potential for chronic pain management, offering significant benefits for public health.

Chronic low back pain (CLBP) is one of the most common chronic musculoskeletal disorders worldwide. Guidelines recommend exercise therapy (ET) in CLBP management, but more research is needed to investigate specific ET modalities and their underlying mechanisms. The primary goal of this study is to evaluate the short-term and long-term effectiveness of a time-contingent individualised high-intensity training (HIT) protocol on disability compared with a time-contingent moderate-intensity training (MIT) as used in usual care, in persons with severely disabling CLBP. Additionally, the effectiveness on central effects, the added value of prolonged training at home and technology support, and the cost-effectiveness are evaluated. In this randomised controlled trial, CLBP patients will be randomly divided into three groups of 56 participants. Group 1, 'TechnoHIT', receives HIT with technology-support in the home-phase. Group 2, 'HIT', receives HIT without technology support. Group 3, 'MIT', receives MIT, reflecting training intensity as used in usual care. The primary outcome is patient-reported disability, measured by the Modified Oswestry Disability Index. Secondary outcomes include quantitative sensory testing, psychosocial factors, broad physical fitness, quality of life, cost-effectiveness, adherence and usability of technology. Trial registration number NCT06491121.

Despite wide endorsement of a biopsychosocial framework for pain, social aspects of pain remain rarely addressed in the context of pain prevention and management. In this review, we aim to 1) examine the broad scope of social determinants and consequences of pain and their interactions across multiple levels of organization, and 2) provide a framework synthesizing existing concepts and potential areas for future work on social aspects of pain, drawing upon socioecological, intersectional, and life course approaches. Integrating interdisciplinary theory and evidence, we outline pathways through which multilevel social factors and pain may affect each other over time. We also provide a brief summary of intrapersonal aspects of pain, which are thought to operate at the interface between individuals and the social context. Progressing from micro- to macrolevel factors, we illustrate how social determinants of pain can directly or indirectly contribute to pain experiences, expression, risk, prognosis, and impact across populations. We consider 1) at the interpersonal level, the roles of social comparison, social relatedness, social support, social exclusion, empathy, and interpersonal conflict; 2) at the group or community level, the roles of intimacy groups, task groups, social categories, and loose associations; and 3) at the societal level, the roles of political, economic, and cultural systems, as well as their policies and practices. We present examples of multilevel consequences of pain across these levels and discuss opportunities to reduce the burden and inequities of pain by expanding multilevel social approaches in pain research and practice. PERSPECTIVE: Despite wide endorsement of a biopsychosocial framework for pain, social aspects of pain are often unclearly defined, hindering their use in pain prevention, management, and research. We summarize the scope of social aspects of pain and provide a framework synthesizing existing concepts and potential areas for future work.

Several studies have documented that higher rates of primary care physicians are associated with lower rates of preventable hospitalizations. Counties with higher rates of preventable hospitalizations are found in the Appalachian and Mississippi (MS) Delta Regions.

(1) To determine if the association of primary care capacity with preventable hospitalizations is different in the Appalachian and MS Delta regions compared to the rest of the U.S., and (2) to explore primary care capacity in counties with lower-than-expected preventable hospitalization rates.

This study modeled preventable hospitalizations with primary care physicians (PCP) per 100,000 (PCP capacity) while controlling for several factors. A spatial regime variable was also included, which modeled Appalachian and MS Delta regions separately. Next, PCP capacity was removed from the model and a geospatial residual analysis was performed to identify geographic clusters of counties with lower-than-expected rates of preventable hospitalizations (bright spots). PCP capacity in bright spots was then compared to that in counties with higher-than-expected rates (cold spots).

Higher PCP capacity was significantly associated with lower rates of preventable hospitalizations in the rest of U.S. model, though was not significant for the Appalachian or MS Delta models. The residual analysis showed that compared to counties with higher-than-expected rates (cold spots), counties with lower-than-expected rates (bright spots) had significantly higher PCP capacity, though not in the MS Delta region.

Consistent with previous literature, it was found that the factors associated with preventable hospitalizations vary by region, though the results are mixed when looking at the Appalachian and MS Delta regions separately. Future research should explore characteristics of bright spots within the Appalachian and MS Delta regions.

Pain is one of the most common concerns among chronically ill older adults. However, access to pain management is not equitable among certain populations, including rural residents. This qualitative study explored rural older adults' experiences with pain and its treatment. Eighteen participants were recruited from rural counties of Alabama, who were age 60+, cognitively intact, community-dwelling, had one or more chronic/serious illnesses, and experienced pain. Open-ended questions were asked in individual interviews, and inductive, thematic analysis was used for data analysis. Findings revealed the impact of pain (physical limitations, psychological distress, and coping strategies), the impact of COVID-19 (physical/mental health and pain management), challenges in pain management in rural areas (lack of provider and healthcare resources, transportation-related issues, mistrust, and limited insurance coverage) and suggestions to address these challenges. Program and policy-level interventions are crucial in improving the resources and education/training needed for effective pain management for rural older adults.

Fibromyalgia (FM) is a multifaceted disease that is often associated with neuropsychiatric disorders and is burdened by a high degree of psychological distress. Non-pharmacological interventions, including physical exercise and complementary therapies, have shown satisfactory results for either physical or psychological FM symptoms.

In this narrative review, we analyzed scientific evidence of moderate to high quality regarding the psychological and neurocognitive effects of physical therapies for FM. A total of 29 studies were selected after searching the PubMed and Google Scholar databases using the combination of terms « fibromyalgia», «psychological distress», «fibrofog», mental disorder», «aerobic exercise», «strength exercise», «Pilates», «Tai chi» and «Yoga».

Aerobic exercise can improve depression, anxiety, stress, mental function and mood, thanks to the remodulation of neurotransmitters and hormones. Strength training, on the other hand, has been shown to alleviate mental confusion, anger and depression. Finally, mind-body disciplines appear to be effective for depression, anxiety, catastrophizing, memory and coping strategies. Based on these findings, we devised an ideal exercise program that could relieve the psychological distress of FM patients, thus interrupting the pathogenic neuroendocrine circuits that lead to the exacerbation of pain and other FM-related symptoms.

Thanks to neuroendocrine remodulation, physical exercise may simultaneously improve the physical and mental health of FM patients. This narrative review collects current evidence on the effects of specific physical interventions on psychological and neurocognitive domains of FM patients and additionally provides an evidence-based training program that could be prescribed to FM patients with high psychological distress or neuropsychiatric symptoms.

Background: Chronic pain (CP) patients frequently feel misunderstood and experience a lack of support. This led to the creation of support telephone lines in some countries. However, there is no scientific data grounding their development or evaluating their performance. Almost 37% of the Portuguese adult population suffers from CP, with great costs for patients and the healthcare system. Methods: To determine the viability of a support line for CP in Portugal, a qualitative study was designed, and online focus group meetings, with patients and healthcare professionals, were conducted. Their perspectives, beliefs, and expectations were evaluated and described. Results: This study revealed that a CP support line is a feasible project from the participants' perspective if its interventions are limited to active listening, emotional support, and tailored suggestions. Conclusions: It has the potential to generate a positive impact on healthcare services, while also contributing to greater equity of access to support.

Chronic pain represents a significant unmet medical need, affecting one-fifth of the U.S. population. EC5026 is a small molecule inhibitor of the enzyme soluble epoxide hydrolase (sEH) which is being developed as a novel non-opioid, non-NSAID analgesic. EC5026 prolongs the action of epoxy fatty acids, endogenous analgesic lipid mediators that are rapidly metabolized by sEH. We evaluated the safety and pharmacokinetic profile of EC5026 in two phase I trials, a single-ascending dose (SAD) study and a fed-fasted study. The SAD study evaluated EC5026 doses ranging from 0.5 to 24 mg in healthy volunteers. EC5026 was well tolerated. No treatment-emergent adverse events were considered related to EC5026. No apparent treatment- or dose-related trends in laboratory results, vital signs, physical examinations, or electrocardiograms were observed. A linear, near-dose-proportional increase in exposure was observed with progressive doses in the SAD study; plasma exposure was below or near the lower limit of quantification after 0.5-2 mg doses. Mean half-lives ranged from 41.8 to 59.1 h. for doses of 8-24 mg, supporting a once-daily dosing regimen. In the fed-fasted study using 8 mg EC5026 tablets, higher peak concentrations (66%) and total exposures (53%) were observed under the fed condition. Plasma concentrations declined in a monoexponential manner with mean half-lives of 59.5 h. in the fed state and 66.9 h. in the fasted state. Future clinical trials using EC5026 for the treatment of pain are justified based on the favorable outcomes from both clinical trials along with preclinical evidence of analgesic activity.