PAIN®最新文献

{"title":"Noninvasive targeted modulation of pain circuits with focused ultrasonic waves.","authors":"Thomas S Riis, Daniel A Feldman, Adam J Losser, Akiko Okifuji, Jan Kubanek","doi":"10.1097/j.pain.0000000000003322","DOIUrl":"10.1097/j.pain.0000000000003322","url":null,"abstract":"<p><strong>Abstract: </strong>Direct interventions into deep brain circuits constitute promising treatment modalities for chronic pain. Cingulotomy and deep brain stimulation targeting the anterior cingulate cortex have shown notable improvements in the unpleasantness of pain, but these interventions require brain surgeries. In this study, we have developed an approach that can modulate this deep brain affective hub entirely noninvasively, using low-intensity transcranial-focused ultrasound. Twenty patients with chronic pain received two 40-minute active or sham stimulation protocols and were monitored for one week in a randomized crossover trial. Sixty percent of subjects experienced a clinically meaningful reduction of pain on day 1 and on day 7 following the active stimulation, while sham stimulation provided such benefits only to 15% and 20% of subjects, respectively. On average, active stimulation reduced pain by 60.0% immediately following the intervention and by 43.0% and 33.0% on days 1 and 7 following the intervention. The corresponding sham levels were 14.4%, 12.3%, and 6.6%. The stimulation was well tolerated, and no adverse events were detected. Side effects were generally mild and resolved within 24 hours. Together, the direct, ultrasonic stimulation of the anterior cingulate cortex offers rapid, clinically meaningful, and durable improvements in pain severity.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"2829-2839"},"PeriodicalIF":5.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The local molecular signature of human peripheral neuropathic pain.","authors":"Oliver P Sandy-Hindmarch, Pao-Sheng Chang, Paulina S Scheuren, Iara De Schoenmacker, Michèle Hubli, Constantinos Loizou, Stephan Wirth, Devendra Mahadevan, Akira Wiberg, Dominic Furniss, Margarita Calvo, David L H Bennett, Franziska Denk, Georgios Baskozos, Annina B Schmid","doi":"10.1097/j.pain.0000000000003472","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003472","url":null,"abstract":"<p><strong>Abstract: </strong>Focal nerve injuries are often associated with neuropathic pain. Preclinical research suggests altered neuroimmune signalling underlies such neuropathic pain; however, its cause remains poorly understood in humans. In this multicentre cohort study, we describe the local cellular and molecular signature of neuropathic pain at the lesion site, using Morton's neuroma as a human model system of neuropathic pain (n = 22; 18 women) compared with nerves from participants without nerve injury (n = 11; 4 women). Immunofluorescent staining revealed demyelination and chronic infiltration of immune cells in Morton's neuroma. RNA bulk sequencing identified 3349 differentially expressed genes between Morton's neuroma and controls. Gene ontology enrichment analysis and weighted gene co-expression network analyses revealed modules specific for host defence and neurogenesis. Deconvolution analysis confirmed higher densities of macrophages and B cells in Morton's neuroma than control samples. Modules associated with defence response, neurogenesis, and muscle system development as well as macrophage cell populations identified by deconvolution correlated with patients' paroxysmal or evoked pain. Of note, we identified a consistently differentially expressed gene signature (MARCO, CD163, STAB1), indicating the presence of a specific M(GC) subset of macrophages. MARCO gene expression correlated with paroxysmal pain. Targeted immunofluorescent analyses confirmed higher densities of intraneural CD163+MARCO+ macrophage subsets in Morton's neuroma. Our findings provide detailed insight into the local molecular signature in the context of human focal nerve injury. There is clear evidence for an ongoing role of the immune system in chronic peripheral neuropathic pain in humans, with macrophages and specifically the M(GC) MARCO+ subset implicated.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716618","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":"Preparing the brain for pain: new insights and potential biomarkers.","authors":"Jason J Kutch","doi":"10.1097/j.pain.0000000000003485","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003485","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771236","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":"Pain catastrophizing and pain anxiety mediate changes in physical function in a mind-body intervention for adults with traumatic orthopedic injuries.","authors":"Katherine E Gnall, Kate N Jochimsen, Julie R Brewer, Jafar Bakhshaie, Ana-Maria Vranceanu","doi":"10.1097/j.pain.0000000000003477","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003477","url":null,"abstract":"<p><strong>Abstract: </strong>Traumatic orthopedic injuries are common and frequently associated with persistent pain, disability, and emotional distress. Risk factors of persistent pain and disability include pain catastrophizing and pain anxiety, though most interventions for orthopedic injuries are primarily biomedical (eg, surgeries, pharmacology, physiotherapy/exercise). The Toolkit for Optimal Recovery (TOR) is a brief, live video mind-body program designed to directly target pain catastrophizing and anxiety in patients with recent traumatic orthopedic injury to prevent persistent disability. This study was a secondary analysis from a recently completed multisite feasibility RCT of TOR compared with Minimally Enhanced Usual Care (MEUC). We examined the extent to which the purported mechanisms of change in TOR (ie, reductions in pain catastrophizing and anxiety) mediate improvement in physical function. Participants with a recent orthopedic trauma (N = 195; Mage = 44.01) recruited from 4 Level I trauma centers were randomized to TOR or MEUC and completed self-report surveys at baseline, postintervention, and follow-up (3 months after baseline). A multiple mediation analysis using multilevel structural equation modeling (MSEM) demonstrated that pain catastrophizing (b = -5.22, SE = 3.02, Bootstrapped 95% CIs = -0.04, -12.37) and pain anxiety (b = -8.45, SE = 3.59, Bootstrapped 95% CIs = -0.04, -12.37) each significantly mediated improvement in physical function. Overall, findings elucidate the mechanistic role of TOR's primary treatment targets (ie, reductions in pain catastrophizing and anxiety) in improving physical function. Findings highlight the importance of targeting pain catastrophizing and pain anxiety early after orthopedic injury through psychosocial interventions such as TOR.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807107","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":"Individual differences in conditioned pain modulation are associated with functional connectivity within the descending antinociceptive pathway.","authors":"Janet Z Li, Emily P Mills, Natalie R Osborne, Joshua C Cheng, Vaidhehi V Sanmugananthan, Rima El-Sayed, Ariana Besik, Junseok A Kim, Rachael L Bosma, Anton Rogachov, Karen D Davis","doi":"10.1097/j.pain.0000000000003478","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003478","url":null,"abstract":"<p><strong>Abstract: </strong>The perception of pain and ability to cope with it varies widely amongst people, which in part could be due to the presence of inhibitory (antinociceptive) or facilitatory (pronociceptive) effects in conditioned pain modulation (CPM). This study examined whether individual differences in CPM reflect functional connectivity (FC) strengths within nodes of the descending antinociceptive pathway (DAP). A heat-based CPM paradigm and resting-state functional magnetic resonance imaging (rs-fMRI) were used to test the hypothesis that an individual's capacity to exhibit inhibitory CPM (changes in test stimuli [TS] pain due to a conditioning stimulus [CS]) reflects FC of the subgenual anterior cingulate cortex (sgACC), periaqueductal gray (PAG), and rostral ventromedial medulla (RVM). A total of 151 healthy participants (72 men, 79 women) underwent CPM testing and rs-fMRI. Three types of CPM were identified based on the effect of the CS on TS pain: (1) Antinociception: CS reduced TS pain in 45% of participants, (2) No-CPM: CS did not change TS pain in 15% of participants, and (3) Pronociception: CS increased TS pain in 40% of participants. Only the Antinociceptive subgroup exhibited FC between the left sgACC and PAG, right sgACC and PAG, and RVM and PAG. Furthermore, only the Antinociceptive subgroup exhibited a correlation of both left and right sgACC-RVM FC (medium effect sizes) with CPM effect magnitude. Women, compared with men were more likely to be categorized as pronociceptive. These data support the proposition that FC of the DAP reflects or contributes to inhibitory CPM.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807851","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":"Trpv1-lineage neuron-expressing Kcnq4 channel modulates itch sensation in mice.","authors":"Qiong Wang, Guodun Zhao, Huijuan Ding, Zihan Wang, Jianwei Wu, Han Huang, Liang Cao, Hongli Wang, Zhaobing Gao, Jing Feng","doi":"10.1097/j.pain.0000000000003479","DOIUrl":"10.1097/j.pain.0000000000003479","url":null,"abstract":"<p><strong>Abstract: </strong>Voltage-gated potassium channel subfamily q member 4 (Kcnq4) is predominantly expressed by hair cells and auditory neurons and regulates the neuronal excitability in the auditory pathway. Although it is further detected in myelinated large-diameter dorsal root ganglia (DRG) neurons in the periphery, the expression and function of Kcnq4 channel in nociceptors remains unknown. Here we showed that Kcnq4 is substantially expressed by unmyelinated small-diameter DRG neurons in both human and mouse. In spite of a dispensable role in acute pain and chronic skin inflammation, Kcnq4 is specifically involved in the regulation of scratching behavior through controlling action potential firing properties, evidenced by the increased neuronal excitability in small-diameter DRG neurons isolated from Kcnq4 deficient mice. Moreover, genetic ablation of Kcnq4 in Trpv1-positive neurons exacerbates both acute and chronic itch behavior in mice. Taken together, our results uncover a functional role of Trpv1-lineage neuron-expressing Kcnq4 channel in the modulation of itch-specific neuronal excitation in the periphery.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668503","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":"Breaking barriers: addressing opioid stigma in chronic pain and opioid use disorder.","authors":"Karlyn A Edwards, Jessica S Merlin, Fiona Webster, Sean C Mackey, Beth D Darnall","doi":"10.1097/j.pain.0000000000003475","DOIUrl":"10.1097/j.pain.0000000000003475","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668488","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":"Enhancing healthcare professionals' biopsychosocial perspective to chronic pain: assessing the impact of implementing an interdisciplinary training program.","authors":"Wouter Munneke, Margot De Kooning, Jo Nijs, Carine Morin, Anne Berquin, Mira Meeus, Jan Hartvigsen, Christophe Demoulin","doi":"10.1097/j.pain.0000000000003403","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003403","url":null,"abstract":"<p><strong>Abstract: </strong>Advancements in clinical science have shown the necessity for a paradigm shift away from a biomedical toward a biopsychosocial approach. Yet, the translation from clinical science into clinical practice is challenging. The aim of this study was to assess the short-term and mid-term changes in pain knowledge and attitudes and guideline-adherent recommendations of healthcare professionals (HCP) by means of an interdisciplinary training program (ITP) about chronic pain. Belgian HCPs, with a priority for medical doctors, physiotherapists, occupational therapists, nurses, psychologists, and pharmacists in primary care, participated in the ITP, which contained 2 e-learning modules and two 7-hour workshops provided in small interdisciplinary groups in 5 cities. The objective of ITP was to improve HCP's competencies for integrating biopsychosocial chronic pain management with a cognitive behavioral approach into clinical practice. Primary outcomes were changes in knowledge and attitudes about pain and guideline-adherent recommendations for continuation of physical activity, sports, and work; avoiding bed rest; and not supporting opioid usage measured through 2 clinical vignettes. They were measured before, immediately after, and 6 months after the ITP. Changes were analyzed using (generalized) linear mixed models. A total of 405 HCPs participated. The knowledge and attitudes about pain scores improved at post-training (Δ = 9.04, 95% confidence interval 7.72-10.36) and at 6-month follow-up (Δ = 7.16, 95% confidence interval 5.73-8.59). After the training program, HCPs provided significantly more recommendations in accordance with clinical guidelines. Thus, an ITP can improve the biopsychosocial perspective of chronic pain management among HCPs in the short-term and mid-term.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625829","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":"Gaining a new footing on molecular mechanisms of neuropathic pain in patients.","authors":"Jayden A O'Brien, Theodore J Price","doi":"10.1097/j.pain.0000000000003473","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003473","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716458","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":"Pharmacologically enabling the degradation of NaV1.8 channels to reduce neuropathic pain.","authors":"Molly K Martin, Raider Rodriguez, Giselle Guerrero, Garrett D Sheehan, Rasheen Powell, Amanda H Klein, Arin Bhattacharjee","doi":"10.1097/j.pain.0000000000003470","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003470","url":null,"abstract":"<p><strong>Abstract: </strong>In phase II clinical trials, NaV1.8 channels were identified as viable targets to treat acute pain. Results were modest, however, and NaV1.8 pore blockers must be given systemically, potentially leading to adverse effects, especially during prolonged use. A local, long-lasting approach is desirable, yet local anesthetics are neither specific nor long-lasting. In lieu of a pore blocker approach, we show a pharmacological method targeting the scaffolding and degradation of NaV1.8 channels, which attenuated neuropathic pain behavior in mice. NaV1.8 channels interact with the WW domain-containing scaffold protein called Magi-1. WW domains are typically found in ubiquitin ligases, and NaV1.8 channels are susceptible to degradation by ubiquitin ligases. Here, we show NaV1.8 and MAGI-1 colocalized in human tissues. We demonstrate that a lipidated peptide derived from the NaV1.8 WW binding domain, at sub-micromolar concentrations, inhibited rodent dorsal root ganglion neuronal firing. The peptide reduced NaV1.8 channel immunoreactivity and tetrodotoxin-resistant currents in human dorsal root ganglion neurons. We found that the lipidated peptide attenuated neuropathic pain behaviors in mice for multiple weeks after a single injection. Our results reveal that the NaV1.8-targeted lipidated peptide provides local and sustained analgesia, serving as a viable alternative to NaV1.8 pore blockers.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605379","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}