Journal of Pain最新文献

{"title":"Glucocorticoid receptor dynamics and neuroinflammation in chronic restraint stress-induced mechanical allodynia in female rats","authors":"Alejandro Pluma-Pluma ,&nbsp;Luis Tovias-Sanchez ,&nbsp;E. Alfonso Romero-Sandoval ,&nbsp;Janet Murbartián","doi":"10.1016/j.jpain.2025.105473","DOIUrl":"10.1016/j.jpain.2025.105473","url":null,"abstract":"<div><div>Chronic stress increases pain in humans and rodents. It is associated with microglial activation, inflammatory mediators (like HMGB1, TNFα, and IL-1β) production, and alterations in the hypothalamic-pituitary-adrenal (HPA) axis that increase levels of glucocorticoids. Although glucocorticoids and their receptors are known for their anti-inflammatory properties, recent studies suggest they may also have pro-inflammatory effects. Glucocorticoids stimulate the expression of various proteins like NLRP3, Iba-1, and NF-κB, potentially contributing to neuroinflammatory processes. However, the role of the glucocorticoid receptor (GR) in the neuroinflammatory process and mechanical allodynia induced by chronic stress has not been explored. We used a chronic restraint stress (RS) model to develop mechanical allodynia in female rats and examined the role of GR. The administration of dexamethasone increased mechanical allodynia, but blocking GR with RU-486 reduced stress-induced mechanical allodynia. Additionally, adrenalectomy prevented the development of mechanical allodynia. We observed that the pharmacological response to the GR antagonist changes over time, indicating that GR’s role shifts from antinociceptive to pronociceptive in chronic RS. Furthermore, chronic RS for 21 and 28 days increased total and phosphorylated GR expression at the dorsal spinal cord and dorsal root ganglia. Higher levels of GR were observed in neurons, microglia, and macrophages. Lastly, RS increased NLRP3, caspase-1, and NF-κB protein expression, which are associated with neuroinflammation and may induce pain sensitivity. Our findings suggest that glucocorticoids from the adrenal gland play a critical role in causing sensitivity to touch in female rats. Additionally, GR is essential in establishing chronic stress-induced allodynia in female rats.</div></div><div><h3>Perspective</h3><div>This paper reports that glucocorticoid receptor (GR) signaling shifts from anti- to pronociceptive in chronic stress, driving mechanical allodynia via neuroinflammation. Dexamethasone enhanced hypersensitivity, while RU-486 and adrenalectomy prevented it. Increased GR and NLRP3 expressions suggest a crucial role for glucocorticoids in stress-induced pain, highlighting GR as a therapeutic target.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"34 ","pages":"Article 105473"},"PeriodicalIF":4.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic postsurgical pain in young children: Prevalence, pain trajectories and physical and psychological prognostic factors","authors":"Guillermo Ceniza-Bordallo ,&nbsp;Andrés Gómez Fraile ,&nbsp;Ibai López-de-Uralde-Villanueva ,&nbsp;Jennifer A. Rabbitts ,&nbsp;Rui Li ,&nbsp;Tonya M. Palermo ,&nbsp;Patricia Martín-Casas","doi":"10.1016/j.jpain.2025.105476","DOIUrl":"10.1016/j.jpain.2025.105476","url":null,"abstract":"<div><div>Prevalence of chronic postsurgical pain (CPSP) and prognostic factors in older children and adolescents have been identified. However, prevalence and prognostic factors in younger children, which may differ from older children, have been minimally studied. Additionally, a significant knowledge gap exists, with few prospective studies investigating long-term outcomes of CPSP in pediatric populations. To address this, our study investigates CPSP prevalence, prognostic factors, and pain trajectories in 4 to 7-year-olds, aiming to enhance understanding within the 24-month period after surgery. Registered under NCT04735211, the study includes 113 young participants (mean age=5.3 years, 35.4% girls) and their parents recruited from a university hospital in Spain. CPSP prevalence was examined at 3, 6, 12, and 24 months post-surgery. Multiple logistic regression models assessed presurgical predictors (child sex, child age, child’s pain intensity, physical health, psychological health, parent pain catastrophizing, fear of pain). Group-based trajectory modeling (GBTM) was used to analyze postsurgical pain trajectories. Results indicate a 35% CPSP prevalence at 3 months, decreasing to 12% at 24 months. Older age (aOR=1.83, 95% CI 1.11–3.03) and higher parent pain catastrophizing (aOR=1.20, 95% CI 1.10–1.31) were associated with CPSP at 3 months. GBTM identified three postsurgical pain trajectories: Low Pain (27.4%), Quick Recovery (53.1%), and Slow Recovery (19.5%). Findings provide novel data in this vulnerable younger age group to help understand prevalence of CPSP, physical and psychological prognostic factors and pain trajectories, which may lead to establishing preventative initiatives.</div></div><div><h3>Perspective</h3><div>This study provides valuable insights into the high prevalence of CPSP, with rates of 35% at 3 months decreasing to 12% at 24 months. It identifies both modifiable (e.g., parent pain catastrophizing, pain intensity, physical health) and non-modifiable (e.g., age) risk factors in a minimally studied population.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"34 ","pages":"Article 105476"},"PeriodicalIF":4.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-106b-5p downregulate KCNQ2 expression contributing to incisional pain in male rats","authors":"Jieshu Zhou MM ,&nbsp;Yi Zhao MD ,&nbsp;Yantong Wan MD ,&nbsp;Xiongxiong Zhong MD ,&nbsp;Qian Liu MD ,&nbsp;Lu Huang MD ,&nbsp;Xiying Chen MD ,&nbsp;Xuemei Lin MD ,&nbsp;Hao Li MD","doi":"10.1016/j.jpain.2025.105472","DOIUrl":"10.1016/j.jpain.2025.105472","url":null,"abstract":"<div><div>The Kv7 (KCNQ) K⁺ channels family controls neuron excitability, making them significant targets in pain management. This study aims to investigate the potential role of Kv7.2 (KCNQ2) in regulating postoperative pain and elucidates its upstream regulatory mechanism. A plantar incision model was established in adult male Sprague-Dawley rats to examine changes in KCNQ2 expression in dorsal root ganglion (DRG) neurons. The results demonstrated that the expression of KCNQ2 in peripheral DRG neurons decreased 4 h and 1 day post-incision. Co-staining of KCNQ2 with CGRP and IB4 was significantly reduced in the incision group. In electrophysiological experiments, XE991 depolarized the resting membrane potential of neurons in the contralateral DRGs, while retigabine hyperpolarized neurons in the ipsilateral incision DRGs. The increased excitability observed following the incision is due to a reduction in M-current. Retigabine significantly reduced Cumulative Pain Score (CPS) and increased Mechanical Withdrawal Threshold (MWT) and Thermal Withdrawal Latency (TWL) at 4 h and 1 day post-incision. Interfering with miR-106b-5p using an adeno-associated virus (AAV) increased the KCNQ2 expression in DRG one day after plantar incision, significantly reduced CPS, and increased MWT and TWL at 4 h and 1 day post-incision. These results suggested that the KCNQ2 ion channel, regulated by miR-106b-5p in the rat dorsal root ganglion (DRG), maybe a target for treating plantar incision pain. PERSPECTIVE: This study elucidates the role of KCNQ2 in modulating incisional pain, providing valuable insights that may aid basic researchers in further exploring pain mechanisms and developing targeted therapeutic strategies.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"34 ","pages":"Article 105472"},"PeriodicalIF":4.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The development and validation of the pain-related stigma scale for adolescents (PReSS-A) with chronic pain.","authors":"Emily O Wakefield, William T Zempsky, Rebecca M Puhl, Susmita Kashikar-Zuck, Mark Connelly, Burel R Goodin, Barbara Edelheit, Vaishali Belamkar, Tolulope Adetayo, Corinne T Evans, Christopher Theriault, Carissa DelGaudio, Mark D Litt","doi":"10.1016/j.jpain.2025.105463","DOIUrl":"10.1016/j.jpain.2025.105463","url":null,"abstract":"<p><p>Adolescents with chronic pain often feel stigmatized by their pain condition. Despite the frequency of stigma in this population, few measures exist to assess pain-related stigma in youth with chronic pain. This study reports on the development and validation of the self-report Pain-related Stigma Scale for Adolescents (PReSS-A). The PReSS-A was designed to assess several dimensions of pain-related stigma (felt stigma, peer stigmatization, internalized stigma, and anticipatory stigma/concealment), and to assess stigma across multiple interpersonal relationships. Reliability, construct validity and factor structure of the instrument were evaluated in youth with chronic pain. The sample consisted of 286 adolescents (aged 12-17) with juvenile fibromyalgia (JFM), other chronic primary musculoskeletal pain conditions (CPMP), juvenile idiopathic arthritis (JIA), and disorders of gut-brain interactions (DGBI). Examination of the underlying structure of the instrument was conducted with exploratory factor analysis. Stigma dimension scores were explored between adolescents with different chronic pain conditions. PReSS-A subscales demonstrated strong internal consistency. Construct validity was established through subscale and total score correlations with complementary constructs. The exploratory factor analysis revealed two broad factors for the PReSS-A: felt stigma and internalized stigma. Majority of the sample reported pain-related stigma from all sources: medical providers, school personnel, family members, and peers. Adolescents with JFM reported significantly higher pain-related stigma than those with other conditions. The PReSS-A can facilitate the advancement of pain-related stigma research among adolescents with varied chronic pain conditions. Future research should focus on the degree to which pain-related stigma influences functioning and social development. PERSPECTIVE: This paper presents the development and psychometric properties of the Pain-related Stigma Scale for Adolescents (PReSS-A) among adolescents with chronic pain. This measure can advance our understanding of pain-related stigma among children and adolescents living with chronic pain.</p>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":" ","pages":"105463"},"PeriodicalIF":4.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rat Hindlimb amputation model shows analgesia and sexually dimorphic cold hypersensitivity with immediate targeted muscle reinnervation","authors":"Jose Lucas Zepeda,&nbsp;Gabriella Mraz,&nbsp;Elizabeth Roth,&nbsp;Dorothee Weihrauch,&nbsp;Gwendolyn Hoben","doi":"10.1016/j.jpain.2025.105460","DOIUrl":"10.1016/j.jpain.2025.105460","url":null,"abstract":"<div><div>Targeted muscle reinnervation (TMR) has been used clinically to reduce pain in amputees, but its underlying analgesic mechanisms remain unclear. We developed a rat below-knee amputation model to evaluate pain outcomes following immediate TMR (iTMR) in both male and female Sprague-Dawley rats. Animals were randomized to amputation-only or amputation with iTMR, and assessed for reflexive pain behaviors (von Frey, pin, and cold hypersensitivity) and spontaneous pain behaviors (guarding, flinching, and sucrose preference as a measure of anhedonia). Retrograde labeling was used to trace sensory and motor neurons and confirm nerve coaptation patterns. iTMR significantly reduced hyperalgesia and anhedonia compared to amputation-only. By four weeks, pin testing showed decreased responses in iTMR rats (25%) compared to controls (51%, p=0.01), and sucrose preference was higher in iTMR rats (76% vs. 43%, p=0.01). Cold sensitivity responses were reduced in iTMR-treated males (49% vs. 100% in amputation-only males, p&lt;0.001), but not in females, indicating sex-specific differences. Histologic analysis demonstrated neuroma formation in amputation-only rats but not in iTMR rats. Retrograde labeling confirmed both sensory and motor axons entered the motor branch post-iTMR. These findings demonstrate that iTMR provides analgesia and prevents neuroma formation following amputation, with cold hypersensitivity responses differing by sex. This supports the utility of the hindlimb iTMR model and highlights the need for continued mechanistic investigation and sex-specific analyses in future studies.</div></div><div><h3>Perspective</h3><div>Using a rat hindlimb amputation model to evaluate iTMR, we demonstrate its potential to mitigate neuropathic pain and symptomatic neuroma formation and reveal sex-specific responses to cold hypersensitivity. These findings indicate the potential clinical utility of iTMR in improving pain outcomes, providing more tailored approaches to pain management in amputees.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"33 ","pages":"Article 105460"},"PeriodicalIF":4.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral voices: Depictions of women’s pain experiences on social media","authors":"Kelly Mazzocca BA ,&nbsp;Tori Langmuir BA ,&nbsp;Jasmine Manan BSc ,&nbsp;Michelle M. Gagnon PhD ,&nbsp;Nicole M. Alberts PhD","doi":"10.1016/j.jpain.2025.105461","DOIUrl":"10.1016/j.jpain.2025.105461","url":null,"abstract":"<div><div>TikTok is a popular social media platform increasingly used to disseminate health information and personal experiences, including among women with pain. Characterizing health-related content can help understand how public perceptions are shaped and guide improvements in patient care. Although women with pain often seek information on social media, little is known about social media content pertaining to women’s pain. In this study, the content, characteristics, and engagement metrics of the top 100 TikTok videos on women’s pain were analyzed. “Women’s pain” was searched on TikTok using TikTok’s proprietary algorithm. A total of 140 videos were retained for preliminary extraction, and the first 100 that met inclusion criteria were analyzed. Qualitative content analysis of video content was performed, leading to the development of 15 content categories. Of these categories, 66.6% (10/15) represented aspects of women’s pain experiences characterized as having a negative tone, including “visual depiction of being in pain,” “minimizing/dismissing/gaslighting women’s pain,” “ineffective pain treatment,” “women’s pain not being investigated enough,” and “assuming women’s pain is due to menstruation, motherhood, or mental health issues.” Descriptive analyses indicated that the top 100 videos had a combined 338.8 million views and 35.1 million likes. Most videos featured non-healthcare providers’ creators (76.0%). Across content categories, the highest engagement rates were observed for the category “women’s pain is not understood by others” (15.0%). Overall, strong negative trends were observed in TikTok video content pertaining to women’s pain. These findings underscore the urgent need for improved pain care for women experiencing pain.</div></div><div><h3>Perspective</h3><div>This article reports on the content, characteristics, and engagement metrics of the top 100 TikTok videos pertaining to women’s pain. These findings provide clinicians and researchers with important insights into women’s pain experiences and have the potential to inform future research, education, and training initiatives aimed at improving women’s pain management.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"33 ","pages":"Article 105461"},"PeriodicalIF":4.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of diurnal cortisol rhythm with chronic pain: Evidence from a prospective cohort study in community-dwelling adults","authors":"Yunlong Liang ,&nbsp;Rui Li ,&nbsp;Laura Fumagalli ,&nbsp;Cara Booker","doi":"10.1016/j.jpain.2025.105458","DOIUrl":"10.1016/j.jpain.2025.105458","url":null,"abstract":"<div><div>Despite clinical evidence linking hypothalamic-pituitary-adrenal (HPA) axis dysfunction to chronic pain, epidemiological findings remained mixed. Data from 1246 respondents aged 34–84 at baseline, obtained from the Midlife in the United States (MIDUS) study and its subproject, the National Study of Daily Experiences (NSDE), were used to examine associations between salivary diurnal cortisol rhythms and chronic pain outcomes over a seven-year follow-up period, using mixed-effects logistic regression models adjusted for sociodemographics, lifestyle, and health-related factors. Furthermore, to examine the role of diurnal cortisol rhythms in the development or persistence of chronic pain, the associations were stratified by chronic pain status at baseline. Over a median follow-up of 7.6 years (IQR 6.3–8.3), blunter declines in early post-wake (0.5–4.5 h after waking, OR = 2.16, 95 % CI = 1.41–3.32, P &lt; 0.001) and mid post-wake (4.5–15 h after waking, OR = 1.93, 95 % CI = 1.28–2.90, P &lt; 0.01) cortisol levels were associated with higher odds of developing chronic multisite pain compared to those who remained pain-free at follow-up. In the same subgroup, a blunted early post-wake cortisol decline was associated with higher odds of developing chronic multisite pain, compared to developing chronic non-multisite pain (OR = 2.73, 95 % CI = 1.49–4.99, P &lt; 0.01). No other robust associations were found. Our results suggest that blunted diurnal cortisol declines may play an important role in chronic multisite pain development.</div></div><div><h3>Perspective</h3><div>This prospective study found that blunting in diurnal cortisol decline was associated with higher odds of developing chronic multisite pain. The rate of diurnal cortisol decline may provide information for identifying at-risk populations.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"33 ","pages":"Article 105458"},"PeriodicalIF":4.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered RVG-exosomes-mediated delivery of siRNAs targeting NMDAR alleviates orofacial neuropathic pain by suppressing central sensitivity","authors":"Yan-Yan Zhang ,&nbsp;Yue-Ling Li ,&nbsp;Qin-Xuan Song ,&nbsp;Ya-Ting Yi ,&nbsp;Yu-Heng Feng ,&nbsp;Yi-Ke Li ,&nbsp;Cheng Zhou ,&nbsp;Chun-Jie Li ,&nbsp;Fei Liu ,&nbsp;Jie-Fei Shen","doi":"10.1016/j.jpain.2025.105457","DOIUrl":"10.1016/j.jpain.2025.105457","url":null,"abstract":"<div><div>Orofacial neuropathic pain (NP) is a common complication in oral clinical practice that severely affects quality of life. However, NP does not currently receive effective medications. Engineered exosomes have great potential as drug delivery systems for treating diseases. Here, patch clamp techniques showed that the deficiency of N-methyl-D-aspartic acid receptor (NMDAR) subunits 2A and 2B reversed the spontaneous excitatory postsynaptic current (sEPSC) frequency and neuronal excitability in the spinal trigeminal nucleus caudalis (SpVc) after injury, which is an effective therapeutic target for NP. Hence, we successfully employed exosomes (EXOs) modified with the nervous system-specific rabies virus glycoprotein (RVG) peptide, which exhibited excellent targeting ability towards N2a-Neuro cells and SpVc tissue. RVG-EXOs loaded with siRNAs of NR2A/B efficiently targeted SpVc neurons, further reducing neuronal excitability and relieving the orofacial NP. Taken together, our study investigated the role of NR2A/B in central nociceptive sensitization and suggested that RVG-EXOs-mediated delivery of siRNAs targeting NR2A and NR2B was effective for orofacial NP treatment.</div></div><div><h3>Perspective</h3><div>This study investigated the crucial role of NMDAR in central sensitization of the SpVc after nerve injury. In this study, we innovatively explored a central targeted drug delivery system based on engineered RVG-EXOs, providing a basis for targeted minimally invasive treatments of orofacial NP.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"33 ","pages":"Article 105457"},"PeriodicalIF":4.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduction of opioid withdrawal symptoms and opioid-induced hyperalgesia by subcutaneous sumatriptan reveals central neuromodulation","authors":"Alessandra Pistolesi ,&nbsp;Francesco De Cesaris ,&nbsp;Daniela Buonvicino ,&nbsp;Alberto Chiarugi","doi":"10.1016/j.jpain.2025.105456","DOIUrl":"10.1016/j.jpain.2025.105456","url":null,"abstract":"<div><div>Triptans are efficacious, largely prescribed antimigraine drugs but where and how they exert their therapeutic effect is debated. Because of the presumed impermeability of the blood brain barrier to triptans, a peripheral antimigraine effect of these drugs have been repeatedly proposed. Recent findings, however, indicate that triptans cross the blood brain barrier, and counteract central nociception in models of pronociceptive sensitization. Here, we investigated the effects of subcutaneous (s.c.) sumatriptan in models of opioid withdrawal and opioid-induced hyperalgesia, two conditions sustained by deranged descending facilitation by the rostral ventromedial medulla (RVM). We found that s.c. sumatriptan injection in morphine-dependent rats 30 min before naloxone-precipitated withdrawal reduced severity of withdrawal symptoms. We also found that at the time of naloxone injection sumatriptan reached contents of 294±19 and 371±30 pg/mg of tissue in the RVM and locus coeruleus, respectively. In keeping with data on morphine withdrawal, s.c. sumatriptan injections suppressed thermal hyperalgesia in rats undergoing repeated dosing of morphine. Sumatriptan affected neither behavioral signs in morphine-dependent rats unexposed to naloxone, nor the extent of the initial antinociceptive response to morphine. Overall, data suggest that peripherally injected sumatriptan reaches CNS concentrations sufficient to exert functional neuromodulation of brainstem regions involved in pronociceptive sensitization and nociplasticity.</div></div><div><h3>Perspective</h3><div>This article reports that sumatriptan reduces symptoms of morphine withdrawal and morphine-induced hyperalgesia. Data suggests that triptans exert their antinociceptive effects through central mechanisms.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"33 ","pages":"Article 105456"},"PeriodicalIF":4.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced trapezius pressure pain threshold in fibromyalgia and opioid use","authors":"Carina Lei ,&nbsp;Su Hyoun Park Ph.D. ,&nbsp;Edna J. Evington Ph.D. ,&nbsp;Morgan A. Rosser M.S. ,&nbsp;Katherine T. Martucci Ph.D.","doi":"10.1016/j.jpain.2025.105455","DOIUrl":"10.1016/j.jpain.2025.105455","url":null,"abstract":"<div><div>While opioid medications are potent analgesics, their usage in chronic pain conditions can paradoxically result in opioid-induced hyperalgesia (i.e., enhanced pain sensitivity). However, among individuals with chronic pain, minimal research has examined the effects of long-term opioid medication on pain sensitivity. To better understand how long-term opioid use impacts pain sensitivity, we measured pressure pain threshold (PPT) of the bilateral trapezius among three cohorts: pain-free controls, individuals with fibromyalgia who were not taking opioids (FMN), and individuals with fibromyalgia who were taking opioids long-term (FMO) (NCT05905419). Across these 3 groups, we also measured depression (BSI-18) and fatigue (PROMIS) to examine their relationships with pain sensitivity. Compared to the control group, dominant-side PPT was significantly reduced in both FMN (p = 0.015) and FMO groups (p = 0.004). However, PPT did not significantly differ between FMO versus FMN groups (p = 0.500). Across the fibromyalgia groups, depression and fatigue were not significantly correlated with PPT. From a co-variate analysis and its associated sensitivity analysis, the results did not change when controlling for age, self-identified race, self-identified ethnicity, and BMI. From an exploratory analysis of the FMO group, individuals who took their last opioid medication dose more recently prior to PPT assessment had higher PPTs (i.e., lower pain sensitivity, p &lt; 0.001). In summary, reduced PPT appears to occur similarly across individuals with fibromyalgia regardless of long-term opioid use status; meanwhile, short-term (i.e., more acute) opioid dose timing- related effects on PPT may occur in individuals with fibromyalgia taking opioids long-term.</div></div><div><h3>Perspective</h3><div>Compared to pain-free controls, we identified significantly lower pressure pain threshold (PPT) in individuals with fibromyalgia. When comparing individuals taking opioids versus not, PPT was similar across groups regardless of opioid use status. Among the opioid-taking individuals, we identified potential opioid-related effects of PPT increase with more recent opioid dose.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"33 ","pages":"Article 105455"},"PeriodicalIF":4.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}