Pub Date : 2025-02-01Epub Date: 2024-08-21DOI: 10.1097/j.pain.0000000000003345
Paul Bautin, Marc-Antoine Fortier, Monica Sean, Graham Little, Marylie Martel, Maxime Descoteaux, Guillaume Léonard, Pascal Tétreault
Abstract: Chronic pain is a pervasive and debilitating condition with increasing implications for public health, affecting millions of individuals worldwide. Despite its high prevalence, the underlying neural mechanisms and pathophysiology remain only partly understood. Since its introduction 35 years ago, brain diffusion magnetic resonance imaging (MRI) has emerged as a powerful tool to investigate changes in white matter microstructure and connectivity associated with chronic pain. This review synthesizes findings from 58 articles that constitute the current research landscape, covering methods and key discoveries. We discuss the evidence supporting the role of altered white matter microstructure and connectivity in chronic primary pain conditions, highlighting the importance of studying multiple chronic pain syndromes to identify common neurobiological pathways. We also explore the prospective clinical utility of diffusion MRI, such as its role in identifying diagnostic, prognostic, and therapeutic biomarkers. Furthermore, we address shortcomings and challenges associated with brain diffusion MRI in chronic primary pain studies, emphasizing the need for the harmonization of data acquisition and analysis methods. We conclude by highlighting emerging approaches and prospective avenues in the field that may provide new insights into the pathophysiology of chronic pain and potential new therapeutic targets. Because of the limited current body of research and unidentified targeted therapeutic strategies, we are forced to conclude that further research is required. However, we believe that brain diffusion MRI presents a promising opportunity for enhancing our understanding of chronic pain and improving clinical outcomes.
{"title":"What has brain diffusion magnetic resonance imaging taught us about chronic primary pain: a narrative review.","authors":"Paul Bautin, Marc-Antoine Fortier, Monica Sean, Graham Little, Marylie Martel, Maxime Descoteaux, Guillaume Léonard, Pascal Tétreault","doi":"10.1097/j.pain.0000000000003345","DOIUrl":"10.1097/j.pain.0000000000003345","url":null,"abstract":"<p><strong>Abstract: </strong>Chronic pain is a pervasive and debilitating condition with increasing implications for public health, affecting millions of individuals worldwide. Despite its high prevalence, the underlying neural mechanisms and pathophysiology remain only partly understood. Since its introduction 35 years ago, brain diffusion magnetic resonance imaging (MRI) has emerged as a powerful tool to investigate changes in white matter microstructure and connectivity associated with chronic pain. This review synthesizes findings from 58 articles that constitute the current research landscape, covering methods and key discoveries. We discuss the evidence supporting the role of altered white matter microstructure and connectivity in chronic primary pain conditions, highlighting the importance of studying multiple chronic pain syndromes to identify common neurobiological pathways. We also explore the prospective clinical utility of diffusion MRI, such as its role in identifying diagnostic, prognostic, and therapeutic biomarkers. Furthermore, we address shortcomings and challenges associated with brain diffusion MRI in chronic primary pain studies, emphasizing the need for the harmonization of data acquisition and analysis methods. We conclude by highlighting emerging approaches and prospective avenues in the field that may provide new insights into the pathophysiology of chronic pain and potential new therapeutic targets. Because of the limited current body of research and unidentified targeted therapeutic strategies, we are forced to conclude that further research is required. However, we believe that brain diffusion MRI presents a promising opportunity for enhancing our understanding of chronic pain and improving clinical outcomes.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"166 2","pages":"243-261"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962401","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}
Pub Date : 2025-02-01Epub Date: 2024-07-09DOI: 10.1097/j.pain.0000000000003324
Amanda B Feinstein, Kimberly Brown, Ashley L Dunn, Alexandra J Neville, Olivia Sokol, Heather Poupore-King, John A Sturgeon, Albert H Kwon, Anya T Griffin
{"title":"Where do we start? Health care transition in adolescents and young adults with chronic primary pain.","authors":"Amanda B Feinstein, Kimberly Brown, Ashley L Dunn, Alexandra J Neville, Olivia Sokol, Heather Poupore-King, John A Sturgeon, Albert H Kwon, Anya T Griffin","doi":"10.1097/j.pain.0000000000003324","DOIUrl":"10.1097/j.pain.0000000000003324","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"236-242"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563972","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}
Pub Date : 2025-02-01Epub Date: 2024-08-26DOI: 10.1097/j.pain.0000000000003349
Chihua Li, Chunyu Liu, Chenfei Ye, Zi Lian, Peiyi Lu
Abstract: Using cross-sectional data from the United States, England, China, and India, we examined the relationship between education and frequent pain, alongside the modification role of gender in this relationship. We further examined patterns of 3 pain dimensions among participants who reported frequent pain, including pain severity, interference with daily activities, and medication use (these pain dimension questions were not administered in all countries). Our analytical sample included 92,204 participants aged 50 years and above. We found a high prevalence of frequent pain across the 4 countries ranging from 28% to 41%. Probit models showed that higher education was associated with lower risk of pain (United States: -0.26, 95% CI: -0.33, -0.19; England: -0.32, 95% CI: -0.39, -0.25; China: -0.33, 95% CI -0.41, -0.26; India: -0.18, 95% CI -0.21, -0.15). Notably, in China and India, the negative association between higher education and frequent pain was less pronounced among women compared with men, which was not observed in the United States or England. Further analysis showed that individuals with higher education experiencing frequent pain reported less severity, fewer daily activity interferences, and less medication use compared with those with lower education. In the United States, these associations were stronger among women. Our findings highlight the prevalent pain among middle-aged and older adults in these 4 countries and emphasize the potentially protective role of higher education on frequent pain, with nuanced gender differences across different settings. This underscores the need for tailored strategies considering educational and gender differences to improve pain management and awareness.
{"title":"Education, gender, and frequent pain among middle-aged and older adults in the United States, England, China, and India.","authors":"Chihua Li, Chunyu Liu, Chenfei Ye, Zi Lian, Peiyi Lu","doi":"10.1097/j.pain.0000000000003349","DOIUrl":"10.1097/j.pain.0000000000003349","url":null,"abstract":"<p><strong>Abstract: </strong>Using cross-sectional data from the United States, England, China, and India, we examined the relationship between education and frequent pain, alongside the modification role of gender in this relationship. We further examined patterns of 3 pain dimensions among participants who reported frequent pain, including pain severity, interference with daily activities, and medication use (these pain dimension questions were not administered in all countries). Our analytical sample included 92,204 participants aged 50 years and above. We found a high prevalence of frequent pain across the 4 countries ranging from 28% to 41%. Probit models showed that higher education was associated with lower risk of pain (United States: -0.26, 95% CI: -0.33, -0.19; England: -0.32, 95% CI: -0.39, -0.25; China: -0.33, 95% CI -0.41, -0.26; India: -0.18, 95% CI -0.21, -0.15). Notably, in China and India, the negative association between higher education and frequent pain was less pronounced among women compared with men, which was not observed in the United States or England. Further analysis showed that individuals with higher education experiencing frequent pain reported less severity, fewer daily activity interferences, and less medication use compared with those with lower education. In the United States, these associations were stronger among women. Our findings highlight the prevalent pain among middle-aged and older adults in these 4 countries and emphasize the potentially protective role of higher education on frequent pain, with nuanced gender differences across different settings. This underscores the need for tailored strategies considering educational and gender differences to improve pain management and awareness.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"388-397"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073523","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}
Pub Date : 2025-02-01Epub Date: 2024-08-30DOI: 10.1097/j.pain.0000000000003374
James Gerhart, John W Burns, Beverly Thorn, Mark Jensen, James Carmody, Francis Keefe
Abstract: Findings suggest that cognitive therapy (CT), mindfulness-based stress reduction (MBSR), and behavior therapy (BT) for chronic pain produce improvements through changes in putative mechanisms. Evidence supporting this notion is largely based on findings showing significant associations between treatment mechanism variables and outcomes. An alternative view is that treatments may work by reducing or decoupling the impact of changes in mechanism variables on changes in outcomes. We examined the degree to which relationships between previous changes in potential treatment mechanisms and subsequent changes in outcomes changed as treatment progressed and vice versa. Cognitive therapy, MBSR, BT, and treatment as usual (TAU) were compared in people with chronic low back pain (N = 521). Eight individual sessions were administered with weekly assessments of putative treatment mechanisms and outcomes. Lagged analyses revealed mechanism × session number interactions and outcome × session number interactions, such that associations between mechanism and outcome variables were strong and significant in the first third of treatment, but weakened over time and became nonsignificant by the last third of treatment. These effects were similar across treatment conditions but did not emerge among people undergoing TAU. Results suggest that during the course of CT, MBSR, and BT, the links between changes in treatment mechanism variables became decoupled from subsequent changes in outcomes and vice versa. Thus, starting by midtreatment and continuing into late treatment, participants may have learned through participation in the treatments that episodes of maladaptive pain-related thoughts and/or spikes in pain need not have detrimental consequences on their subsequent experience.
摘要:研究结果表明,认知疗法(CT)、正念减压疗法(MBSR)和行为疗法(BT)通过改变假定机制来改善慢性疼痛。支持这一观点的证据主要基于治疗机制变量与治疗结果之间存在显著关联的研究结果。另一种观点认为,治疗方法可能通过减少或解除机制变量变化对结果变化的影响而发挥作用。我们研究了潜在治疗机制的先前变化与后续结果变化之间的关系随治疗进展而变化的程度,反之亦然。我们对慢性腰背痛患者(521 人)的认知疗法、MBSR、BT 和常规治疗(TAU)进行了比较。共进行了八次单独治疗,每周对假定的治疗机制和结果进行评估。滞后分析显示了机制×疗程数交互作用和结果×疗程数交互作用,因此机制和结果变量之间的关联在治疗的前三分之一时间内是强烈和显著的,但随着时间的推移逐渐减弱,到治疗的最后三分之一时间变得不显著。这些效应在不同的治疗条件下相似,但在接受 TAU 治疗的人群中没有出现。结果表明,在 CT、MBSR 和 BT 治疗过程中,治疗机制变量的变化与后续结果变化之间的联系变得不相关,反之亦然。因此,从治疗中期开始,一直到治疗后期,参与者通过参与治疗可能已经了解到,与疼痛相关的适应不良想法和/或疼痛峰值的发作不一定会对他们随后的经历产生不利影响。
{"title":"Treatment mechanism and outcome decoupling effects in cognitive therapy, mindfulness-based stress reduction, and behavior therapy for chronic pain.","authors":"James Gerhart, John W Burns, Beverly Thorn, Mark Jensen, James Carmody, Francis Keefe","doi":"10.1097/j.pain.0000000000003374","DOIUrl":"10.1097/j.pain.0000000000003374","url":null,"abstract":"<p><strong>Abstract: </strong>Findings suggest that cognitive therapy (CT), mindfulness-based stress reduction (MBSR), and behavior therapy (BT) for chronic pain produce improvements through changes in putative mechanisms. Evidence supporting this notion is largely based on findings showing significant associations between treatment mechanism variables and outcomes. An alternative view is that treatments may work by reducing or decoupling the impact of changes in mechanism variables on changes in outcomes. We examined the degree to which relationships between previous changes in potential treatment mechanisms and subsequent changes in outcomes changed as treatment progressed and vice versa. Cognitive therapy, MBSR, BT, and treatment as usual (TAU) were compared in people with chronic low back pain (N = 521). Eight individual sessions were administered with weekly assessments of putative treatment mechanisms and outcomes. Lagged analyses revealed mechanism × session number interactions and outcome × session number interactions, such that associations between mechanism and outcome variables were strong and significant in the first third of treatment, but weakened over time and became nonsignificant by the last third of treatment. These effects were similar across treatment conditions but did not emerge among people undergoing TAU. Results suggest that during the course of CT, MBSR, and BT, the links between changes in treatment mechanism variables became decoupled from subsequent changes in outcomes and vice versa. Thus, starting by midtreatment and continuing into late treatment, participants may have learned through participation in the treatments that episodes of maladaptive pain-related thoughts and/or spikes in pain need not have detrimental consequences on their subsequent experience.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"408-419"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120428","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}
Pub Date : 2025-02-01Epub Date: 2024-09-03DOI: 10.1097/j.pain.0000000000003380
Helen Koechlin, Cosima Locher, Antonia Barke, Beatrice Korwisi
{"title":"Retrospective identification of the diagnosis of chronic primary musculoskeletal pain: a pragmatic suggestion by The Pain Net.","authors":"Helen Koechlin, Cosima Locher, Antonia Barke, Beatrice Korwisi","doi":"10.1097/j.pain.0000000000003380","DOIUrl":"10.1097/j.pain.0000000000003380","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"311-314"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036613","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}
Pub Date : 2025-02-01Epub Date: 2024-08-26DOI: 10.1097/j.pain.0000000000003344
Mats Kirkeby Fjeld, Anders Pedersen Årnes, Bo Engdahl, Bente Morseth, Laila Arnesdatter Hopstock, Alexander Horsch, Audun Stubhaug, Bjørn Heine Strand, Anette Hylen Ranhoff, Dagfinn Matre, Christopher Sivert Nielsen, Ólöf Anna Steingrímsdóttir
Abstract: Paradoxical associations have been observed for leisure-time physical activity (LTPA) and occupational physical activity (OPA) and several health-related outcomes. Typically, higher LTPA is associated with health benefits and high OPA with health hazards. Using data from the Tromsø Study (2015-2016), we assessed how questionnaire-based LTPA and OPA (n = 21,083) and accelerometer-measured physical activity (PA) (n = 6778) relate to pain outcomes. Leisure-time physical activity and OPA were categorized as inactive PA, low PA, and moderate-to-vigorous PA and then aggregated into 9 levels, eg, inactive LTPA/inactive OPA. Accelerometer-measured PA included counts/minute, steps/day, and WHO PA recommendations from 2010 to 2020. Three binary pain outcomes (any pain, any chronic pain, and moderate-to-severe chronic pain) were constructed based on pain location, intensity, duration, and impact on daily activities. By using Poisson regression to estimate absolute and relative associations, we found that high LTPA was associated with lower pain prevalence and vice versa for OPA. Compared to inactive LTPA, prevalence ratio (PR) with 95% confidence intervals was lowest for moderate-to-vigorous LTPA, 0.93 (0.89-0.96) for any pain, 0.88 (0.84-0.93) for any chronic pain, and 0.66 (0.59-0.75) for moderate-to-severe chronic pain. Compared to sedentary OPA, the ratio was highest for moderate-to-vigorous OPA, 1.04 (1.01-1.07) for any pain, 1.06 (1.02-1.10) for any chronic pain, and 1.33 (1.21-1.46) for moderate-to-severe chronic pain. Aggregated LTPA and OPA showed lower outcomes for moderate-to-vigorous LTPA combined with lower levels of OPA. Higher levels of accelerometer-measured PA were associated with less pain. To summarize, we found inverse associations for LTPA and OPA. Benefits from LTPA seem to depend on low levels of OPA.
{"title":"The physical activity paradox; exploring the relationship with pain outcomes. The Tromsø Study 2015-2016.","authors":"Mats Kirkeby Fjeld, Anders Pedersen Årnes, Bo Engdahl, Bente Morseth, Laila Arnesdatter Hopstock, Alexander Horsch, Audun Stubhaug, Bjørn Heine Strand, Anette Hylen Ranhoff, Dagfinn Matre, Christopher Sivert Nielsen, Ólöf Anna Steingrímsdóttir","doi":"10.1097/j.pain.0000000000003344","DOIUrl":"10.1097/j.pain.0000000000003344","url":null,"abstract":"<p><strong>Abstract: </strong>Paradoxical associations have been observed for leisure-time physical activity (LTPA) and occupational physical activity (OPA) and several health-related outcomes. Typically, higher LTPA is associated with health benefits and high OPA with health hazards. Using data from the Tromsø Study (2015-2016), we assessed how questionnaire-based LTPA and OPA (n = 21,083) and accelerometer-measured physical activity (PA) (n = 6778) relate to pain outcomes. Leisure-time physical activity and OPA were categorized as inactive PA, low PA, and moderate-to-vigorous PA and then aggregated into 9 levels, eg, inactive LTPA/inactive OPA. Accelerometer-measured PA included counts/minute, steps/day, and WHO PA recommendations from 2010 to 2020. Three binary pain outcomes (any pain, any chronic pain, and moderate-to-severe chronic pain) were constructed based on pain location, intensity, duration, and impact on daily activities. By using Poisson regression to estimate absolute and relative associations, we found that high LTPA was associated with lower pain prevalence and vice versa for OPA. Compared to inactive LTPA, prevalence ratio (PR) with 95% confidence intervals was lowest for moderate-to-vigorous LTPA, 0.93 (0.89-0.96) for any pain, 0.88 (0.84-0.93) for any chronic pain, and 0.66 (0.59-0.75) for moderate-to-severe chronic pain. Compared to sedentary OPA, the ratio was highest for moderate-to-vigorous OPA, 1.04 (1.01-1.07) for any pain, 1.06 (1.02-1.10) for any chronic pain, and 1.33 (1.21-1.46) for moderate-to-severe chronic pain. Aggregated LTPA and OPA showed lower outcomes for moderate-to-vigorous LTPA combined with lower levels of OPA. Higher levels of accelerometer-measured PA were associated with less pain. To summarize, we found inverse associations for LTPA and OPA. Benefits from LTPA seem to depend on low levels of OPA.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"315-327"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120427","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}
Pub Date : 2025-02-01Epub Date: 2024-10-10DOI: 10.1097/j.pain.0000000000003454
Sara Muller, James Bailey, Ram Bajpai, Toby Helliwell, Sarah A Harrisson, Rebecca Whittle, Christian D Mallen, Julie Ashworth
{"title":"Further evidence on gabapentinoid efficacy is required but work in this field will be challenging.","authors":"Sara Muller, James Bailey, Ram Bajpai, Toby Helliwell, Sarah A Harrisson, Rebecca Whittle, Christian D Mallen, Julie Ashworth","doi":"10.1097/j.pain.0000000000003454","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003454","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"166 2","pages":"464-465"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962381","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}
Pub Date : 2025-02-01Epub Date: 2024-09-19DOI: 10.1097/j.pain.0000000000003395
Sulayman D Dib-Hajj, Stephen G Waxman
{"title":"Species-specific differences and the role of Na v 1.9 in pain pathophysiology.","authors":"Sulayman D Dib-Hajj, Stephen G Waxman","doi":"10.1097/j.pain.0000000000003395","DOIUrl":"10.1097/j.pain.0000000000003395","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"231-233"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293020","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}
Pub Date : 2025-02-01Epub Date: 2024-07-18DOI: 10.1097/j.pain.0000000000003334
Laura A Payne, Laura C Seidman, Vitaly Napadow, Lisa D Nickerson, Poornima Kumar
Abstract: Menstrual pain is associated with deficits in central pain processing, yet neuroimaging studies to date have all been limited by focusing on group comparisons of adult women with vs without menstrual pain. This study aimed to investigate the role of the triple network model (TNM) of brain networks in adolescent girls with varied menstrual pain severity ratings. One hundred participants (ages 13-19 years) completed a 6-min resting state functional magnetic resonance imaging (fMRI) scan and rated menstrual pain severity, menstrual pain interference, and cumulative menstrual pain exposure. Imaging analyses included age and gynecological age (years since menarche) as covariates. Menstrual pain severity was positively associated with functional connectivity between the cingulo-opercular salience network (cSN) and the sensory processing regions, limbic regions, and insula, and was also positively associated with connectivity between the left central executive network (CEN) and posterior regions. Menstrual pain interference was positively associated with connectivity between the cSN and widespread brain areas. In addition, menstrual pain interference was positively associated with connectivity within the left CEN, whereas connectivity both within the right CEN and between the right CEN and cortical areas outside the network (including the insula) were negatively associated with menstrual pain interference. Cumulative menstrual pain exposure shared a strong negative association with connectivity between the default mode network and other widespread regions associated with large-scale brain networks. These findings support a key role for the involvement of TNM brain networks in menstrual pain characteristics and suggest that alterations in pain processing exist in adolescents with varying levels of menstrual pain.
{"title":"Functional connectivity associations with menstrual pain characteristics in adolescents: an investigation of the triple network model.","authors":"Laura A Payne, Laura C Seidman, Vitaly Napadow, Lisa D Nickerson, Poornima Kumar","doi":"10.1097/j.pain.0000000000003334","DOIUrl":"10.1097/j.pain.0000000000003334","url":null,"abstract":"<p><strong>Abstract: </strong>Menstrual pain is associated with deficits in central pain processing, yet neuroimaging studies to date have all been limited by focusing on group comparisons of adult women with vs without menstrual pain. This study aimed to investigate the role of the triple network model (TNM) of brain networks in adolescent girls with varied menstrual pain severity ratings. One hundred participants (ages 13-19 years) completed a 6-min resting state functional magnetic resonance imaging (fMRI) scan and rated menstrual pain severity, menstrual pain interference, and cumulative menstrual pain exposure. Imaging analyses included age and gynecological age (years since menarche) as covariates. Menstrual pain severity was positively associated with functional connectivity between the cingulo-opercular salience network (cSN) and the sensory processing regions, limbic regions, and insula, and was also positively associated with connectivity between the left central executive network (CEN) and posterior regions. Menstrual pain interference was positively associated with connectivity between the cSN and widespread brain areas. In addition, menstrual pain interference was positively associated with connectivity within the left CEN, whereas connectivity both within the right CEN and between the right CEN and cortical areas outside the network (including the insula) were negatively associated with menstrual pain interference. Cumulative menstrual pain exposure shared a strong negative association with connectivity between the default mode network and other widespread regions associated with large-scale brain networks. These findings support a key role for the involvement of TNM brain networks in menstrual pain characteristics and suggest that alterations in pain processing exist in adolescents with varying levels of menstrual pain.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"338-346"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748835","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}
Pub Date : 2025-02-01Epub Date: 2024-08-13DOI: 10.1097/j.pain.0000000000003361
Qian Xu, Qin Zheng, Xiang Cui, Andrew Cleland, Juan Hincapie, Srinivasa N Raja, Xinzhong Dong, Yun Guan
Abstract: Spinal cord stimulation (SCS) is an effective modality for pain treatment, yet its underlying mechanisms remain elusive. Neurokinin 1 receptor-positive (NK1R + ) neurons in spinal lamina I play a pivotal role in pain transmission. To enhance our mechanistic understanding of SCS-induced analgesia, we investigated how different SCS paradigms modulate the activation of NK1R + neurons, by developing NK1R-Cre;GCaMP6s transgenic mice and using in vivo calcium imaging of superficial NK1R + neurons under anesthesia (1.5% isoflurane). Neurokinin 1 receptor-positive neurons in the lumbar spinal cord (L4-5) showed a greater activation by electrical test stimulation (TS, 3.0 mA, 1 Hz) at the hindpaw at 2 weeks after tibia-sparing nerve injury (SNI-t) than in naïve mice. Spinal cord stimulation was then delivered through a bipolar plate electrode placed epidurally at L1-2 level. The short-term 50-Hz high-intensity SCS (80% motor threshold [MoT], 10 minutes) induced robust and prolonged inhibition of NK1R + neuronal responses to TS in both naïve and SNI-t mice. The 30-minute 50-Hz and 900-Hz SCS applied at moderate intensity (50% MoT) also significantly inhibited neuronal responses in SNI-t mice. However, at low intensity (20% MoT), the 30-minute 900-Hz SCS only induced persistent neuronal inhibition in naïve mice, but not in SNI-t mice. In conclusion, both 10-minute high-intensity SCS and 30-minute SCS at moderate intensity inhibit the activation of superficial NK1R + neurons, potentially attenuating spinal nociceptive transmission. Furthermore, in vivo calcium imaging of NK1R + neurons provides a new approach for exploring the spinal neuronal mechanisms of pain inhibition by neuromodulation pain therapies.
{"title":"Visualizing the modulation of neurokinin 1 receptor-positive neurons in the superficial dorsal horn by spinal cord stimulation in vivo.","authors":"Qian Xu, Qin Zheng, Xiang Cui, Andrew Cleland, Juan Hincapie, Srinivasa N Raja, Xinzhong Dong, Yun Guan","doi":"10.1097/j.pain.0000000000003361","DOIUrl":"10.1097/j.pain.0000000000003361","url":null,"abstract":"<p><strong>Abstract: </strong>Spinal cord stimulation (SCS) is an effective modality for pain treatment, yet its underlying mechanisms remain elusive. Neurokinin 1 receptor-positive (NK1R + ) neurons in spinal lamina I play a pivotal role in pain transmission. To enhance our mechanistic understanding of SCS-induced analgesia, we investigated how different SCS paradigms modulate the activation of NK1R + neurons, by developing NK1R-Cre;GCaMP6s transgenic mice and using in vivo calcium imaging of superficial NK1R + neurons under anesthesia (1.5% isoflurane). Neurokinin 1 receptor-positive neurons in the lumbar spinal cord (L4-5) showed a greater activation by electrical test stimulation (TS, 3.0 mA, 1 Hz) at the hindpaw at 2 weeks after tibia-sparing nerve injury (SNI-t) than in naïve mice. Spinal cord stimulation was then delivered through a bipolar plate electrode placed epidurally at L1-2 level. The short-term 50-Hz high-intensity SCS (80% motor threshold [MoT], 10 minutes) induced robust and prolonged inhibition of NK1R + neuronal responses to TS in both naïve and SNI-t mice. The 30-minute 50-Hz and 900-Hz SCS applied at moderate intensity (50% MoT) also significantly inhibited neuronal responses in SNI-t mice. However, at low intensity (20% MoT), the 30-minute 900-Hz SCS only induced persistent neuronal inhibition in naïve mice, but not in SNI-t mice. In conclusion, both 10-minute high-intensity SCS and 30-minute SCS at moderate intensity inhibit the activation of superficial NK1R + neurons, potentially attenuating spinal nociceptive transmission. Furthermore, in vivo calcium imaging of NK1R + neurons provides a new approach for exploring the spinal neuronal mechanisms of pain inhibition by neuromodulation pain therapies.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"428-437"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976326","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}