Pain Reports最新文献

{"title":"Pregabalin produces analgesia in males but not females in an animal model of chronic widespread muscle pain.","authors":"Ashley N Plumb, Kazuhiro Hayashi, Adam Janowski, Angela Smith, Lynn Rasmussen, Kathleen A Sluka, Joseph B Lesnak","doi":"10.1097/PR9.0000000000001207","DOIUrl":"10.1097/PR9.0000000000001207","url":null,"abstract":"<p><strong>Introduction: </strong>Pregabalin, which acts on the α₂δ-1 subunit of voltage-gated calcium channels, relieves ≥50% of pain in a third of individuals with fibromyalgia. Thus far, preclinical studies of pregabalin have predominantly used male animals.</p><p><strong>Objectives: </strong>The purpose of our study was to investigate potential sex differences in the analgesic efficacy of pregabalin that may contribute to disparities in human outcomes.</p><p><strong>Methods: </strong>We used a mouse model of chronic widespread muscle pain (CWP) to test the effects of pregabalin on muscle hyperalgesia, nonreflexive pain, and motor behaviors. The CWP pain model combines 2 pH 4.0 saline injections, spaced 5 days apart, into the gastrocnemius muscle and produces bilateral muscle hyperalgesia. Furthermore, we explored sex differences in the mRNA and protein expression of the α₂δ-1 subunit of voltage-gated calcium channels in the dorsal horn of the spinal cord and dorsal root ganglia after development of CWP.</p><p><strong>Results: </strong>Pregabalin fully attenuated muscle hyperalgesia bilaterally in male but not female mice with equal motor deficits produced in both sexes. In addition, using the conditioned place preference test, mice of both sexes with CWP spent significantly more time in the pregabalin-paired chamber compared with baseline, but not significantly greater than pain-free controls. Chronic widespread muscle pain produced no changes in α₂δ-1 subunit mRNA or protein expression in the dorsal horn of the spinal cord or dorsal root ganglia in either sex.</p><p><strong>Conclusion: </strong>Overall, these findings indicate pregabalin may be more effective in treating CWP in males, but the factors leading to these differences are not fully understood.</p>","PeriodicalId":52189,"journal":{"name":"Pain Reports","volume":"9 6","pages":"e1207"},"PeriodicalIF":3.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated manual therapies: IASP taskforce viewpoint.","authors":"Jerry Draper-Rodi, Dave Newell, Mary F Barbe, Joel Bialosky","doi":"10.1097/PR9.0000000000001192","DOIUrl":"10.1097/PR9.0000000000001192","url":null,"abstract":"<p><strong>Introduction: </strong>Manual therapy refers to a range of hands-on interventions used by various clinical professionals, such as osteopaths, osteopathic physicians, chiropractors, massage therapists, physiotherapists, and physical therapists, to treat patients experiencing pain.</p><p><strong>Objectives: </strong>To present existing evidence of mechanisms and clinical effectiveness of manual therapy in pain.</p><p><strong>Methods: </strong>This Clinical Update focuses on the 2023 International Association for the Study of Pain Global Year for Integrative Pain Care. Current models of manual therapy and examples of integrative manual therapy are discussed.</p><p><strong>Results: </strong>The evolution of concepts in recent years are presented and current gaps in knowledge to guide future research highlighted. Mechanisms of manual therapy are discussed, including specific and contextual effects. Findings from research on animal and humans in manual therapy are presented including on inflammatory markers, fibrosis, and behaviours. There is low to moderate levels of evidence that the effect sizes for manual therapy range from small to large for pain and function in tension headache, cervicogenic headache, fibromyalgia, low back pain, neck pain, knee pain, and hip pain.</p><p><strong>Conclusion: </strong>Manual therapies appear to be effective for a variety of conditions with minimal safety concerns. There are opportunities for manual therapies to integrate new evidence in its educational, clinical, and research models. Manual therapies are also well-suited to fostering a person-centred approach to care, requiring the clinician to relinquish some of their power to the person consulting. Integrated manual therapies have recently demonstrated a fascinating evolution illustrating their adaptability and capacity to address contemporary societal challenges.</p>","PeriodicalId":52189,"journal":{"name":"Pain Reports","volume":"9 6","pages":"e1192"},"PeriodicalIF":3.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multisensory sensitivity in relation to pain: a scoping review of terminology and assessment.","authors":"Harper Dunne, Laura A Frey-Law","doi":"10.1097/PR9.0000000000001193","DOIUrl":"10.1097/PR9.0000000000001193","url":null,"abstract":"<p><p>Chronic pain is a debilitating health problem affecting 20 million Americans annually. Most patients with chronic pain report negative impacts on daily function and quality of life, which can result in devastating emotional and financial stress. Although the causes of chronic pain remain elusive, there is increasing interest in sensitivity to everyday sensory stimuli as it relates to chronic pain, potentially serving as an indirect marker of altered central nervous system sensory processing. However, sensitivity to multiple sensory inputs, eg, bright lights, certain fabrics, loud noises, etc, is described using multiple terminologies. The lack of a common vocabulary makes it difficult to find and summarize related discoveries, potentially inhibiting scientific progress. Thus, the purpose of this scoping review was to identify and characterize the terminology used in publications assessing some form of multisensory sensitivity as it relates to pain (eg, a pain cohort or pain sensitivity). Our review of 6 databases (PubMed, Scopus, Embase, CINAHL, PsycINFO+, and Cochrane) comprehensively cataloged peer-reviewed studies published through March 2023 in this domain. Of 12,841 possible studies identified, 92 met all inclusion criteria, with over 80% being published in the last decade. A wide range of terminology has been used for this construct, likely in part a result of the many different professional disciplines represented. These results provide valuable insights for future development of a standardized vocabulary and serve as a resource to aid future investigators of multisensory sensitivity and pain in their study design.</p>","PeriodicalId":52189,"journal":{"name":"Pain Reports","volume":"9 6","pages":"e1193"},"PeriodicalIF":3.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep and circadian rhythm disturbances as risk and progression factors for multiple chronic overlapping pain conditions: a protocol for a longitudinal study.","authors":"Chung Jung Mun, Shawn D Youngstedt, Megan E Petrov, Keenan A Pituch, Jeffrey A Elliott, Steven Z George, Frank LoVecchio, Aram S Mardian, Kit K Elam, Nina Winsick, Ryan Eckert, Surabhi Sajith, Kate Alperin, Ananya Lakhotia, Kaylee Kohler, Matthew J Reid, Mary C Davis, Roger B Fillingim","doi":"10.1097/PR9.0000000000001194","DOIUrl":"10.1097/PR9.0000000000001194","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic overlapping pain conditions (COPCs), such as chronic low back pain (cLBP) and fibromyalgia, frequently cooccur and incur substantial healthcare costs. However, to date, much focus has been placed on individual anatomically based chronic pain conditions, whereas little is known about the mechanisms underlying progression to multiple (more than 1) COPCs. This study aims to address the gap by investigating the role of common and modifiable risk factors, specifically sleep and circadian rhythm disturbances, in the development of multiple COPCs.</p><p><strong>Methods: </strong>The study will enroll 300 participants with cLBP, including 200 with cLBP only and 100 with cLBP plus other COPCs (ie, fibromyalgia, temporomandibular disorders, irritable bowel syndrome, and chronic headaches) and follow them up for 12 months. Sleep and circadian rhythms will be assessed using wireless sleep electroencephalography, 24-hour evaluation of the rhythm of urinary 6-sulfatoxymelatonin, actigraphy, and sleep diaries. Pain amplification using quantitative sensory testing, psychological distress using validated self-report measures, and the number of pain sites using a pain body map will also be assessed.</p><p><strong>Perspectives: </strong>This research aims to (1) comprehensively characterize sleep/circadian disturbances in individuals with single and multiple COPCs using multimodal in-home assessments; (2) examine the associations between sleep/circadian disturbances, changes in pain amplification, and psychological distress; and (3) investigate the relationship among these factors and the progression in the number of pain sites, a proxy for multiple COPCs. The findings will provide insights into the mechanisms leading to multiple COPCs, potentially informing treatment and prevention strategies for these complex conditions.</p>","PeriodicalId":52189,"journal":{"name":"Pain Reports","volume":"9 6","pages":"e1194"},"PeriodicalIF":3.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miRNA packaging into small extracellular vesicles and implications in pain.","authors":"Jason T DaCunza, Jason R Wickman, Seena K Ajit","doi":"10.1097/PR9.0000000000001198","DOIUrl":"10.1097/PR9.0000000000001198","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are a heterogenous group of lipid bilayer bound particles naturally released by cells. These vesicles are classified based on their biogenesis pathway and diameter. The overlap in size of exosomes generated from the exosomal pathway and macrovesicles that are pinched off from the surface of the plasma membrane makes it challenging to isolate pure populations. Hence, isolated vesicles that are less than 200 nm are called small extracellular vesicles (sEVs). Extracellular vesicles transport a variety of cargo molecules, and multiple mechanisms govern the packaging of cargo into sEVs. Here, we discuss the current understanding of how miRNAs are targeted into sEVs, including the role of RNA binding proteins and EXOmotif sequences present in miRNAs in sEV loading. Several studies in human pain disorders and rodent models of pain have reported alterations in sEV cargo, including miRNAs. The sorting mechanisms and target regulation of miR-939, a miRNA altered in individuals with complex regional pain syndrome, is discussed in the context of inflammation. We also provide a broad overview of the therapeutic strategies being pursued to utilize sEVs in the clinic and the work needed to further our understanding of EVs to successfully deploy sEVs as a pain therapeutic.</p>","PeriodicalId":52189,"journal":{"name":"Pain Reports","volume":"9 6","pages":"e1198"},"PeriodicalIF":3.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-374 family is a key regulator of chronic primary pain onset.","authors":"Nathaniel P Hernandez, Ashleigh Rawls, Jiegen Chen, Xin Zhang, Yaomin Wang, Xianglong Gao, Marc Parisien, Mohamad Karaky, Carolina Beraldo Meloto, Francesca Montagna, Hong Dang, Yue Pan, Ying Zhao, Samuel McLean, Sarah Linnstaedt, Luda Diatchenko, Andrea G Nackley","doi":"10.1097/PR9.0000000000001199","DOIUrl":"10.1097/PR9.0000000000001199","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic primary pain conditions (CPPCs) are linked to catecholamine activation of peripheral adrenergic receptors. Yet, catecholamine-dependent epigenetic mechanisms, such as microRNA (miRNA) regulation of mRNA transcripts, remain largely unknown.</p><p><strong>Objectives: </strong>We sought to identify RNA species correlated with case status in 3 pain cohorts, to validate RNAs found to be dysregulated in a mouse model of CPPC onset, and to directly test the role of adrenergic receptors in miRNA regulation. Furthermore, we tested antinociceptive effects of miR-374 overexpression.</p><p><strong>Methods: </strong>We used RNA-seq and quantitative reverse transcription polymerase chain reaction to measure RNA expression in 3 pain cohorts. Next, we validated identified RNAs with quantitative reverse transcription polymerase chain reaction in a mouse model of CPPC onset, measuring expression in plasma, peripheral (adipose, muscle, dorsal root ganglia [DRG]), and central (spinal cord) tissues. Then, we stimulated adrenergic receptors in primary adipocyte and DRG cultures to directly test regulation of microRNAs by adrenergic signaling. Furthermore, we used in vitro calcium imaging to measure the antinociceptive effects of miR-374 overexpression.</p><p><strong>Results: </strong>We found that one miRNA family, miR-374, was downregulated in the plasma of individuals with temporomandibular disorder, fibromyalgia syndrome, or widespread pain following a motor vehicle collision. miR-374 was also downregulated in plasma, white adipose tissue, and spinal cord from mice with multisite mechanical sensitivity. miR-374 downregulation in plasma and spinal cord was female specific. Norepinephrine stimulation of primary adipocytes, but not DRG, led to decreased miR-374 expression. Furthermore, we identified tissue-specific and sex-specific changes in the expression of predicted miR-374 mRNA targets, including known (HIF1A, NUMB, TGFBR2) and new (ATXN7, CRK-II) pain targets. Finally, we demonstrated that miR-374 overexpression in DRG neurons reduced capsaicin-induced nociceptor activity.</p><p><strong>Conclusions: </strong>Downregulation of miR-374 occurs between adrenergic receptor activation and mechanical hypersensitivity, and its adipocyte source implicates adipose signaling in nociception. Further study of miR-374 may inform therapeutic strategies for the millions worldwide who experience CPPCs.</p>","PeriodicalId":52189,"journal":{"name":"Pain Reports","volume":"9 6","pages":"e1199"},"PeriodicalIF":3.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of a holistic composite outcome measure for the evaluation of chronic pain interventions.","authors":"Rod S Taylor, Quinton Neville, Christopher M Mullin, Nagy A Mekhail, Jan W Kallewaard, Salim Hayek, Jason E Pope, Corey W Hunter, Shrif J Costandi, Leonardo Kapural, Christopher A Gilmore, Erika A Petersen, Kiran V Patel, Sam Eldabe, Robert M Levy, Christopher Gilligan, Shravani Durbhakula, Alaa Abd-Elsayed, Marshall Bedder, Patrick Buchanan, Erin Hanson, Angela Leitner, Nicole Soliday, Rui V Duarte, Daniel J Clauw, Turo J Nurmikko","doi":"10.1097/PR9.0000000000001202","DOIUrl":"10.1097/PR9.0000000000001202","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic pain is a personal experience influenced by multiple biopsychosocial factors. Using a pain intensity measure alone to assess the effectiveness of a chronic pain intervention fails to fully evaluate its impact on the multifaceted chronic pain experience. The holistic minimal clinically important difference (MCID) is a composite outcome developed to provide a comprehensive assessment of chronic pain in response to intervention, across 5 outcome domains: pain intensity, health-related quality of life, sleep quality, physical, and emotional function. To focus on domains where the individual need is greatest, the holistic MCID reflects the cumulative MCID averaged over only the domains where subjects were impaired preintervention.</p><p><strong>Objectives: </strong>To assess the internal and construct validity of the Holistic MCID score to inform its future use as an evidence-based tool.</p><p><strong>Methods: </strong>This validation study was undertaken using data from the EVOKE trial with 111 patients up to 24-month follow-up. Internal consistency of the holistic MCID was assessed using Cronbach alpha statistic and dimensional exploration using principal component analysis.</p><p><strong>Results: </strong>The holistic MCID measure demonstrated strong internal consistency with Cronbach alpha >0.7 at all follow-ups. Principal component analysis showed one overarching holistic dimension to be present in the composite. Construct validity was demonstrated by an increase in the holistic MCID score being associated with both increased Patients' Global Impression of Change, EuroQol visual analogue scale score, and each of the outcome domains in a \"leave-one-out\" analysis (all <i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>The holistic MCID provides a valid measure for the comprehensive, personalized assessment of response after a chronic pain intervention. The validity of the holistic MCID requires further confirmation in other chronic pain populations and with different interventions.</p>","PeriodicalId":52189,"journal":{"name":"Pain Reports","volume":"9 6","pages":"e1202"},"PeriodicalIF":3.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating associations between social risks and health care utilization in patients with chronic low back pain.","authors":"Sang S Pak, Yuxi Jiang, Dmytro S Lituiev, Emilia H De Marchis, Thomas A Peterson","doi":"10.1097/PR9.0000000000001191","DOIUrl":"10.1097/PR9.0000000000001191","url":null,"abstract":"<p><strong>Introduction: </strong>Care and outcomes for patients with chronic low back pain (cLBP) are influenced by the social risk factors that they experience. Social risk factors such as food insecurity and housing instability have detrimental effects on patient health and wellness, healthcare outcomes, and health disparities.</p><p><strong>Objectives: </strong>This retrospective cross-sectional study examined how social risk factors identified in unstructured and structured electronic health record (EHR) data for 1,295 patients with cLBP were associated with health care utilization. We also studied the impact of social risk factors, controlling for back pain-related disability on health care utilization.</p><p><strong>Methods: </strong>Included patients who received outpatient spine and/or physical therapy services at an urban academic medical center between 2018 and 2020. Five identified social risks were financial insecurity, housing instability, food insecurity, transportation barriers, and social isolation. Outcomes included 4 categories of health care utilization: emergency department (ED) visits/hospitalizations, imaging, outpatient specialty visits related to spine care, and physical therapy (PT) visits. Poisson regression models tested associations between the presence of identified social risks and each outcome measure.</p><p><strong>Results: </strong>Identified social risks in 12.8% of the study population (N = 166/1,295). In multivariate models, social isolation was positively associated with imaging, specialty visits, and PT visits; housing instability was positively associated with ED visits/hospitalizations and imaging; food insecurity was positively associated with ED visits/hospitalizations and specialty visits but negatively associated with PT visits; and financial strain was positively associated with PT visits but negatively associated with ED visits/hospitalization.</p><p><strong>Conclusion: </strong>These associations were seen above and beyond other factors used as markers of socioeconomic marginalization, including neighborhood-level social determinants of health, race/ethnicity, and insurance type. Identifying and intervening on social risk factors that patients with cLBP experience may improve outcomes and be cost-saving.</p>","PeriodicalId":52189,"journal":{"name":"Pain Reports","volume":"9 6","pages":"e1191"},"PeriodicalIF":3.1,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex Regional Pain Syndrome: a cross-sectional study of physical symptoms, disability, and psychological health in long term.","authors":"Ellen Lyckegård Finn, Astrid Parinder, Erika Nyman, Lars B Dahlin","doi":"10.1097/PR9.0000000000001180","DOIUrl":"10.1097/PR9.0000000000001180","url":null,"abstract":"<p><strong>Introduction: </strong>Knowledge about long-time residual symptoms, disabilities, and psychological health in complex regional pain syndrome (CRPS) is limited.</p><p><strong>Objectives: </strong>The aim was to evaluate outcome, focusing on physical symptoms, disability, and psychological health, in individuals with CRPS through a cross-sectional survey study.</p><p><strong>Methods: </strong>Individuals with a confirmed diagnosis of CRPS were identified through medical charts and sent validated survey forms (Disabilities of the Arm, Shoulder and Hand-Quick version, Specific Hand Surgery Questionnaire-8 questions, EuroQol 5 Dimensions 3 levels, Life Satisfaction Questionnaire-11, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, and Sense of Coherence-29) and complementary questions.</p><p><strong>Results: </strong>Responders (response rate: 99/238, 42%; CRPS type 1: 72%; CRPS type 2: 28%; time since diagnosis median: 59 [34-94] months) reported remaining symptoms and disability (Disabilities of the Arm, Shoulder and Hand-Quick version score: 45 [20-70]) and more improvement in type 1 than in type 2. Only 9% of individuals with CRPS reported no residual pain or discomfort. Approximately 60% had problems in daily activities, 49% had sleeping problems, and 90% experienced moderate-extreme pain with 23% still on sick leave. The Hospital Anxiety and Depression Scale survey revealed significantly higher scores than a Swedish reference population. Individuals with a low Sense of Coherence and high pain catastrophizing had worse disability and were less satisfied with their lives and physical and psychological health. A lower level of education and more anxiety were associated with worsened disability over time.</p><p><strong>Conclusion: </strong>Individuals with CRPS suffer in the long term from pain, sleeping problems, and limitations in daily activities with occurrence of anxiety and depression, resulting in dissatisfaction with many aspects of their lives. A low Sense of Coherence and high pain catastrophizing are associated with a worse outcome. Biopsychosocial aspects should be addressed in clinical practice.</p>","PeriodicalId":52189,"journal":{"name":"Pain Reports","volume":"9 5","pages":"e1180"},"PeriodicalIF":3.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11419548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained nerve growth factor-induced C-nociceptor sensitization to electrical sinusoidal stimulation in humans.","authors":"Hans Jürgen Solinski, Martin Schmelz, Roman Rukwied","doi":"10.1097/PR9.0000000000001190","DOIUrl":"10.1097/PR9.0000000000001190","url":null,"abstract":"<p><strong>Introduction: </strong>Injection of recombinant human nerve growth factor (rhNGF) evokes acute heat and prolonged \"polymodal\" (mechanosensitive [CM]) and \"silent\" (mechano<i>in</i>sensitive [CMi]) C-nociceptor sensitization. Both nociceptor classes can be activated differentially using slowly depolarizing electrical sinusoidal stimuli.</p><p><strong>Objectives: </strong>To explore the temporal profile of nociceptor sensitization to heat and mechanical and electrical stimuli in humans after rhNGF.</p><p><strong>Methods: </strong>Recombinant human nerve growth factor (1 µg) and NaCl (0.9%) was injected into human forearm skin (n = 9, 50 µL/injection). Pain ratings (numeric rating scale) to transcutaneous electrical stimuli (1 ms 20 Hz rectangular pulses, 500-ms half-period sine wave [1 Hz] and 4 Hz sine wave pulses [2.5 and 60 seconds]) were assessed at days 3, 21, and 49 after injection, in addition to heat pain thresholds (HPTs, 9 × 9 mm thermode) and mechanical impact pain (4 and 8 m/second).</p><p><strong>Results: </strong>Suprathreshold sinusoidal stimulation for specific CM (1 Hz) and combined CM and CMi (4 Hz) activation resulted in enhanced pain from day 3 post rhNGF and lasted throughout 7 weeks. These temporal dynamics contrasted minimum HPTs at day 3 (normalized by day 49) or mechanical impact pain (developing slowly until day 21 before declining depending on stimulus intensity). Correlation analyses of electrical pain indicated diverging kinetics when assessed for CM with or without concomitant CMi activation at days 3 and 21, which converged 7 weeks post rhNGF.</p><p><strong>Conclusions: </strong>Exceptionally long sensitization of CM and CMi nociceptors by rhNGF, uncovered by suprathreshold electrical sinusoidal stimulation, indicates a signal transduction-independent long-lasting hyperexcitability of C-nociceptors that clinically may contribute to rhNGF-maintained chronic inflammatory pain.</p>","PeriodicalId":52189,"journal":{"name":"Pain Reports","volume":"9 5","pages":"e1190"},"PeriodicalIF":3.4,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11419415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}