PAIN®最新文献

{"title":"Human cold pain: a randomized crossover trial.","authors":"Felix J Resch, Stefan Heber, Farzin Shahi, Manuel Zauner, Cosmin I Ciotu, Andreas Gleiss, Sabine Sator, Michael J M Fischer","doi":"10.1097/j.pain.0000000000003503","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003503","url":null,"abstract":"<p><strong>Abstract: </strong>The mechanism causing cold pain in humans is unresolved. Animal data suggest a nonredundant contribution to cold pain for transient receptor potential channels TRPM8 and TRPA1 for detection and voltage-gated sodium channels NaV1.7 and NaV1.8 for conduction at these temperatures. We established an intradermal injection-based cold pain model, which allows pharmacologically addressing molecular targets at the site of cooling. Lidocaine, added to the injection solution as positive control, largely reduced cold-induced pain in 36 volunteers. The 4 mentioned molecular targets were blocked by antagonists in a double-blinded crossover trial. Pain induced by 3°C intradermal fluid was not reduced to a relevant extent by any of the 4 antagonists alone or by the quadruple combination. However, the temperature threshold for cold pain appeared shifted by the inhibition of TRPA1, TRPM8, and NaV1.7 and to a lesser extent by NaV1.8 inhibition, 4-fold inhibition decreased the threshold by 5.8°C. Further mechanisms contributing to human cold pain need to be considered.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signatures of chronic pain in multiple sclerosis: a machine learning approach to investigate trigeminal neuralgia.","authors":"Timur H Latypov, Abigail Wolfensohn, Rose Yakubov, Jerry Li, Patcharaporn Srisaikaew, Daniel Jörgens, Ashley Jones, Errol Colak, David Mikulis, Frank Rudzicz, Jiwon Oh, Mojgan Hodaie","doi":"10.1097/j.pain.0000000000003497","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003497","url":null,"abstract":"<p><strong>Abstract: </strong>Chronic pain is a pervasive, disabling, and understudied feature of multiple sclerosis (MS), a progressive demyelinating and neurodegenerative disease. Current focus on motor components of MS disability combined with difficulties assessing pain symptoms present a challenge for the evaluation and management of pain in MS, highlighting the need for novel methods of assessment of neural signatures of chronic pain in MS. We investigate chronic pain in MS using MS-related trigeminal neuralgia (MS-TN) as a model condition focusing on gray matter structures as predictors of chronic pain. T1 imaging data from people with MS (n = 75) and MS-TN (n = 77) using machine learning (ML) was analyzed to derive imaging predictors at the level of cortex and subcortical gray matter. The ML classifier compared imaging metrics of patients with MS and MS-TN and distinguished between these conditions with 93.4% individual average testing accuracy. Structures within default-mode, somatomotor, salience, and visual networks (including hippocampus, primary somatosensory cortex, occipital cortex, and thalamic subnuclei) were identified as significant imaging predictors of trigeminal neuralgia pain. Our results emphasize the multifaceted nature of chronic pain and demonstrate the utility of imaging and ML in assessing and understanding MS-TN with greater objectivity.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical proof-of-concept results with a novel TRPA1 antagonist (LY3526318) in 3 chronic pain states.","authors":"Marcia M Mellado Lagarde, Darren Wilbraham, Ricardo Fonseca Martins, Heather Shi Zhao, Kimberley Jackson, Kirk W Johnson, Kelly L Knopp, David DiBenedetto, Lisa M Broad","doi":"10.1097/j.pain.0000000000003487","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003487","url":null,"abstract":"<p><strong>Abstract: </strong>Transient receptor potential ankyrin 1 (TRPA1) is implicated in physiological and pathological nociceptive signaling, but the clinical benefit of TRPA1 antagonists in chronic pain is not clearly demonstrated. LY3526318 is an oral, potent, and selective novel TRPA1 antagonist. The Chronic Pain Master Protocol was used to evaluate the safety and efficacy of LY3526318 in 3 randomized, placebo-controlled, proof-of-concept studies in knee osteoarthritis pain (OA), chronic low back pain (CLBP), and diabetic peripheral neuropathic pain (DPNP). Participants were randomized (1:2, placebo:LY3526318, 250 mg daily) into an 8-week double-blinded period. At 4 weeks, participants treated with LY3526318 transitioned to a placebo. The primary endpoint was the self-reported daily pain intensity measured using a Numerical Rating Scale (NRS) at 4 weeks. All endpoints were collected for up to 8 weeks. Change from baseline in average weekly NRS was analyzed using Bayesian mixed model repeated measures in the OA (N = 160), CLBP (N = 159), and DPNP (N = 154) studies. Baseline characteristics were balanced between treatment arms. Mean NRS change from baseline to week 4 did not differ significantly between placebo and LY3526318; however, a numerical improvement was observed in the CLBP, not in the OA or DPNP populations. Safety analysis integrated across studies enhanced understanding of the safety profile of LY3526318. LY3526318 showed a potential drug-induced hepatotoxic effect posing a risk for clinical development. No other safety signals were identified. LY3526318 showed potential for different responses among chronic pain indications and patient subpopulations, highlighting challenges in developing TRPA1 antagonists but supporting their value as a target in managing chronic pain.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A call to action to integrate best practice assessment of sexual orientation and gender identity in pain research and clinical care.","authors":"Lauren E Harrison, Katelynn E Boerner, William Black, Sarah Nelson, Melissa Santos, Laura E Simons, Emily O Wakefield, Jacqueline N Warner, Anna C Wilson, Anna Zajacova","doi":"10.1097/j.pain.0000000000003481","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003481","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of gabapentin and antidepressants on opioid-related mortality rates: physicians who can \"see and hear,\" must also \"look and listen\".","authors":"Steven P Cohen","doi":"10.1097/j.pain.0000000000003449","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003449","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in noninvasive brain stimulation: exploring repetitive transcranial magnetic stimulation of the posterior superior insula for pain relief.","authors":"Giulia Liberati","doi":"10.1097/j.pain.0000000000003489","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003489","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Posterior-superior insula repetitive transcranial magnetic stimulation reduces experimental tonic pain and pain-related cortical inhibition in humans.","authors":"Nahian S Chowdhury, Samantha K Millard, Enrico de Martino, Dennis Boye Larsen, David A Seminowicz, Siobhan M Schabrun, Daniel Ciampi de Andrade, Thomas Graven-Nielsen","doi":"10.1097/j.pain.0000000000003488","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003488","url":null,"abstract":"<p><strong>Abstract: </strong>High frequency repetitive transcranial magnetic stimulation (rTMS) to the posterior-superior insula (PSI) may produce analgesic effects. However, the alterations in cortical activity during PSI-rTMS analgesia remain poorly understood. The present study aimed to determine whether tonic capsaicin-induced pain and cortical inhibition (indexed using TMS-electroencephalography) are modulated by PSI-rTMS. Twenty healthy volunteers (10 females) attended 2 sessions randomized to active or sham rTMS. Experimental pain was induced by capsaicin administered to the forearm for 90 minutes, with pain ratings collected every 5 minutes. Left PSI-rTMS was delivered (10 Hz, 100 pulses per train, 15 trains) ∼50 minutes postcapsaicin administration. Transcranial magnetic stimulation-evoked potentials (TEPs) and thermal sensitivity were assessed at baseline, during capsaicin pain prior to rTMS and after rTMS. Bayesian evidence of reduced pain scores and increased heat pain thresholds were found after active rTMS, with no changes occurring after sham rTMS. Pain (prior to active rTMS) led to an increase in the frontal negative peak ∼45 ms (N45) TEP relative to baseline. After active rTMS, there was a decrease in the N45 peak back to baseline levels. In contrast, after sham rTMS, the N45 peak was increased relative to baseline. We also found that the reduction in pain numerical rating scale scores after active vs sham rTMS was correlated with and partially mediated by decreases in the N45 peak. These findings provide evidence of the analgesic effects of PSI-rTMS and suggest that the TEP N45 peak is a potential marker and mediator of both pain and analgesia. This study demonstrates that high-frequency rTMS targeting the posterior-superior insula reduces capsaicin-induced pain and alters cortical activity, with changes in the N45 TMS-evoked potential peak mediating the analgesic effects.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reorganization of lateral habenula neuronal connectivity underlies pain-related impairment in spatial memory encoding.","authors":"Helder Cardoso-Cruz, Clara Monteiro, Vasco Galhardo","doi":"10.1097/j.pain.0000000000003493","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003493","url":null,"abstract":"<p><strong>Abstract: </strong>Dysfunctional hyperactivity of the lateral habenula nucleus (LHb) has emerged as a critical marker for pain-related mood impairments. Acting as a central hub, the LHb filters and disseminates pertinent information to other brain structures during learning. However, it is not well understood how intra-LHb activity is altered during cognitive demand under neuropathic pain conditions. To address this gap, we implanted an optrode structure to record neuronal activity in adult male CD (rat strain without definition) rats during the execution of a delayed nonmatch-to-sample (DNMS) spatial working memory (WM) task. We selectively modulated intra-LHb network activity by optogenetically inhibiting local LHb CaMKIIα (calcium calmodulin-dependent protein kinase II alpha)-expressing neurons during the delay phase of the DNMS task. Behavioral assessments were conducted using a persistent rodent model of neuropathic pain-spared nerve injury. Our results showed that the induction of neuropathic pain disrupted WM encoding accuracy and intra-LHb functional neuronal connectivity. This disruption was reversed by optogenetic inhibition of LHb CaMKIIα-expressing neurons, which also produced antinociceptive effects. Together, our findings provide insight into how intra-LHb networks reorganize information to support different task contexts, suggesting that the abnormal pain-related intra-LHb dynamic segregation of information may contribute to poor cognitive accuracy in male rodents during pain experiences.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of pain expectancy and its confidence in placebo hypoalgesia and nocebo hyperalgesia.","authors":"Eleonora Maria Camerone, Giorgia Tosi, Daniele Romano","doi":"10.1097/j.pain.0000000000003495","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003495","url":null,"abstract":"<p><strong>Abstract: </strong>Placebo hypoalgesia and nocebo hyperalgesia, which exemplify the impact of expectations on pain, have recently been conceptualised as Bayesian inferential processes, yet empirical evidence remains limited. Here, we explore whether these phenomena can be unified within the same Bayesian framework by testing the predictive role of expectations and their level of precision (ie, expectation confidence) on pain, with both predictors measured at the metacognitive level. Sixty healthy volunteers underwent a pain test (ie, 8 noxious electrical stimuli) before (Baseline) and after (T0, T1, T2) receiving a sham treatment associated with hypoalgesic (placebo), hyperalgesic (nocebo), or neutral (control) verbal suggestions, depending on group allocation. Trial-by-trial expectations, their precision, and perceived pain were measured. Skin conductance response (SCR) was also recorded as an autonomic response marker. Bayesian linear mixed models analyses revealed that, for both placebo and nocebo, pain was predicted by expectations alone and by their interaction with expectations precision. In addition, the discrepancy between expected and perceived pain was predicted by expectation precision, with greater alignment between expected and perceived pain when precision was higher. This suggests that both placebo and nocebo responses are well described from a Bayesian perspective. A main effect of time for SCR was observed, suggesting habituation to painful stimuli. Our data provide evidence indicating that both placebo hypoalgesia and nocebo hyperalgesia can be unified within the same Bayesian framework in which not only expectations but also their level of precision, both measured at the metacognitive level, are key determinants of the pain inferential process.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The implementation of infant pain practice change resource to improve infant procedural pain practices: a hybrid type 1 effectiveness-implementation study.","authors":"Bonnie Stevens, Mariana Bueno, Melanie Barwick, Marsha Campbell-Yeo, Christine Chambers, Carole Estabrooks, Rachel Flynn, Sharyn Gibbins, Denise Harrison, Wanrudee Isaranuwatchai, Sylvie LeMay, Melanie Noel, Jennifer Stinson, Anne Synnes, Charles Victor, Janet Yamada","doi":"10.1097/j.pain.0000000000003496","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003496","url":null,"abstract":"<p><strong>Abstract: </strong>Implementation of infant pain practice change (ImPaC) is a multifaceted web-based resource to support pain practice change in neonatal intensive care unit (NICU). We evaluated the (1) intervention effectiveness and (2) implementation effectiveness of ImPaC using a hybrid type 1 effectiveness-implementation study (ie, cluster randomized controlled trial and longitudinal descriptive study). Eligible level 2 and 3 Canadian NICUs were randomized to intervention (INT) or waitlisted to usual care (UC) for 6 months. We assessed the number of painful procedures, proportion of procedures accompanied by valid assessment and evidence-based treatment, and pain intensity to determine intervention effectiveness using intention-to-treat (ITT) and wait-list (WL) analyses. Implementation feasibility and fidelity were explored. Twenty-three NICUs participated (12 INT, 11 UC). Thirty infants/NICU were included in the ITT (INT = 354, UC = 325) and the WL (INT = 678, UC = 325) analyses. In the ITT analysis, the average number of painful procedures/infant/day was lower in the INT group [2.62 (±3.47) vs 3.85 (±4.13), P < 0.001] than in the UC group. Pain assessment was greater in the INT group (34.7% vs 25.5%, P < 0.001) and pain intensity scores were lower [1.47 (1.25) vs 1.86 (1.97); P = 0.029]. Similarly, in the WL analysis, there were fewer painful procedures/infant/day [3.11 (±3.98) vs 3.85 (±4.13), P = 0.003] and increased pain assessment (30.4% vs 25.5%, P = 0.0001) and treatment (31.2% vs 24.0%, P < 0.001) in the INT group. Feasibility and implementation fidelity were associated with improved clinical outcomes.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}