Pub Date : 2024-08-26DOI: 10.1097/j.pain.0000000000003355
Hannah Schmidt, Armin Drusko, Malika Pia Renz, Lea Schlömp, Heike Tost, Sigrid Schuh-Hofer, Jonas Tesarz, Andreas Meyer-Lindenberg, Rolf-Detlef Treede
Abstract: The concept "nociplastic pain" has been developed for patients with features of nociceptive system sensitization that are not explained as nociceptive or neuropathic. Here, we tested how well the recently published grading system differentiates between chronic primary and secondary pain conditions. We recruited patients with fibromyalgia (FMS, n = 41), complex regional pain syndrome (CRPS, n = 11), osteoarthritis (OA, n = 21), or peripheral nerve injury (PNI, n = 8). We used clinical history, pain drawings, quantitative sensory testing (QST), and questionnaires to classify their pains as possibly or probably "nociplastic." All patients with chronic primary pain exhibited widespread/regional pain not explainable by either nociceptive or neuropathic mechanisms. Widespread pain occurred in 12 patients with OA but was identified as nociceptive in 11 of 12. Regional pain occurred in 4 patients with PNI but was identified as neuropathic in 3 of 4. At this step, the grading system had 100% sensitivity and 93% specificity. Clinical evidence for pain hypersensitivity by QST, and history of hypersensitivity and mental comorbidities did not differentiate between chronic primary pain (QST: 36/52 = 69%, history: 43/52 = 83%) and secondary pain conditions (QST: 20/29 = 69%, history: 24/29 83%). Based on these data, specificity remained excellent (93%), but sensitivity dropped substantially (60%) due to lacking evidence for pain hypersensitivity in many patients with FMS. This low sensitivity suggests that the published grading system is not suitable for screening purposes. We suggest structural and content modifications to improve sensitivity, including placement of patient history before clinical examination and addition of a high tender point count as evidence for widespread pain hypersensitivity.
{"title":"Application of the grading system for \"nociplastic pain\" in chronic primary and chronic secondary pain conditions: a field study.","authors":"Hannah Schmidt, Armin Drusko, Malika Pia Renz, Lea Schlömp, Heike Tost, Sigrid Schuh-Hofer, Jonas Tesarz, Andreas Meyer-Lindenberg, Rolf-Detlef Treede","doi":"10.1097/j.pain.0000000000003355","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003355","url":null,"abstract":"<p><strong>Abstract: </strong>The concept \"nociplastic pain\" has been developed for patients with features of nociceptive system sensitization that are not explained as nociceptive or neuropathic. Here, we tested how well the recently published grading system differentiates between chronic primary and secondary pain conditions. We recruited patients with fibromyalgia (FMS, n = 41), complex regional pain syndrome (CRPS, n = 11), osteoarthritis (OA, n = 21), or peripheral nerve injury (PNI, n = 8). We used clinical history, pain drawings, quantitative sensory testing (QST), and questionnaires to classify their pains as possibly or probably \"nociplastic.\" All patients with chronic primary pain exhibited widespread/regional pain not explainable by either nociceptive or neuropathic mechanisms. Widespread pain occurred in 12 patients with OA but was identified as nociceptive in 11 of 12. Regional pain occurred in 4 patients with PNI but was identified as neuropathic in 3 of 4. At this step, the grading system had 100% sensitivity and 93% specificity. Clinical evidence for pain hypersensitivity by QST, and history of hypersensitivity and mental comorbidities did not differentiate between chronic primary pain (QST: 36/52 = 69%, history: 43/52 = 83%) and secondary pain conditions (QST: 20/29 = 69%, history: 24/29 83%). Based on these data, specificity remained excellent (93%), but sensitivity dropped substantially (60%) due to lacking evidence for pain hypersensitivity in many patients with FMS. This low sensitivity suggests that the published grading system is not suitable for screening purposes. We suggest structural and content modifications to improve sensitivity, including placement of patient history before clinical examination and addition of a high tender point count as evidence for widespread pain hypersensitivity.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073522","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 : 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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-26","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 : 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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-26","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 : 2024-08-23DOI: 10.1097/j.pain.0000000000003325
Paraskevi Sgourdou, Melanie Schaffler, Kyuhyun Choi, Nora M McCall, Justin Burdge, Joelle Williams, Gregory Corder, Marc V Fuccillo, Ishmail Abdus-Saboor, Douglas J Epstein
Abstract: The thalamus plays an important role in sensory and motor information processing by mediating communication between the periphery and the cerebral cortex. Alterations in thalamic development have profound consequences on sensory and motor function. In this study, we investigated a mouse model in which thalamic nuclei formation is disrupted because of the absence of Sonic hedgehog (Shh) expression from 2 key signaling centers that are required for embryonic forebrain development. The resulting defects observed in distinct thalamic sensory nuclei in Shh mutant embryos persisted into adulthood prompting us to examine their effect on behavioral responses to somatosensory stimulation. Our findings reveal a role for first-order posterior medial thalamic neurons and their projections to layer 4 of the secondary somatosensory cortex in the transmission of nociceptive information. Together, these results establish a connection between a neurodevelopmental lesion in the thalamus and a modality-specific disruption in pain perception.
{"title":"Impaired pain in mice lacking first-order posterior medial thalamic neurons.","authors":"Paraskevi Sgourdou, Melanie Schaffler, Kyuhyun Choi, Nora M McCall, Justin Burdge, Joelle Williams, Gregory Corder, Marc V Fuccillo, Ishmail Abdus-Saboor, Douglas J Epstein","doi":"10.1097/j.pain.0000000000003325","DOIUrl":"10.1097/j.pain.0000000000003325","url":null,"abstract":"<p><strong>Abstract: </strong>The thalamus plays an important role in sensory and motor information processing by mediating communication between the periphery and the cerebral cortex. Alterations in thalamic development have profound consequences on sensory and motor function. In this study, we investigated a mouse model in which thalamic nuclei formation is disrupted because of the absence of Sonic hedgehog (Shh) expression from 2 key signaling centers that are required for embryonic forebrain development. The resulting defects observed in distinct thalamic sensory nuclei in Shh mutant embryos persisted into adulthood prompting us to examine their effect on behavioral responses to somatosensory stimulation. Our findings reveal a role for first-order posterior medial thalamic neurons and their projections to layer 4 of the secondary somatosensory cortex in the transmission of nociceptive information. Together, these results establish a connection between a neurodevelopmental lesion in the thalamus and a modality-specific disruption in pain perception.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073524","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 : 2024-08-21DOI: 10.1097/j.pain.0000000000003382
Emma E Biggs, Inge Timmers, Lauren C Heathcote, Alexandra G Tremblay-McGaw, Melanie Noel, David Borsook, Laura E Simons
Abstract: Memory biases for pain-related information may contribute to the development and maintenance of chronic pain; however, evidence for when (and for whom) these biases occur is mixed. Therefore, we examined neural, stress, and psychological factors that could influence memory bias, focusing on memories that motivate disabling behaviors: pain perception, conditioned responses to threat-and-safety cues, and responses to aversive nonnoxious stimuli. Two studies were conducted with adolescents with and without chronic pain. Data from 58 participants were included in study 1 (chronic pain n = 34, pain free n = 24, mean age = 16 years), and 39 participants were included in study 2 (chronic pain n = 26, pain free n = 13, mean age = 16 years). Both studies used a threat-safety learning paradigm with memory recall (≈1 month later). Participants completed structural and functional (resting-state) magnetic resonance imaging, salivary cortisol measurements, and self-report measures. Adolescents with pain and pain-free peers consistently recalled being more afraid of safety cues (CS-) and, during heightened stress at encoding (higher cortisol levels), also reported being more afraid of threat cues (CS+). However, no memory bias was present for the emotional response to an aversive stimulus (US; loud scream) or for the recall of pain intensity. Functional connectivity of the amygdala and hippocampus with memory circuits related to the degree of memory bias, but the specific connections varied between the studies, and we observed no relationship between memory bias and brain morphology. Our findings highlight the value of considering the interaction between implicit and explicit memory systems, contributing to a more comprehensive understanding of emotional memory biases in the context of chronic pain.
{"title":"Emotional memory bias in adolescents with chronic pain: examining the relationship with neural, stress, and psychological factors.","authors":"Emma E Biggs, Inge Timmers, Lauren C Heathcote, Alexandra G Tremblay-McGaw, Melanie Noel, David Borsook, Laura E Simons","doi":"10.1097/j.pain.0000000000003382","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003382","url":null,"abstract":"<p><strong>Abstract: </strong>Memory biases for pain-related information may contribute to the development and maintenance of chronic pain; however, evidence for when (and for whom) these biases occur is mixed. Therefore, we examined neural, stress, and psychological factors that could influence memory bias, focusing on memories that motivate disabling behaviors: pain perception, conditioned responses to threat-and-safety cues, and responses to aversive nonnoxious stimuli. Two studies were conducted with adolescents with and without chronic pain. Data from 58 participants were included in study 1 (chronic pain n = 34, pain free n = 24, mean age = 16 years), and 39 participants were included in study 2 (chronic pain n = 26, pain free n = 13, mean age = 16 years). Both studies used a threat-safety learning paradigm with memory recall (≈1 month later). Participants completed structural and functional (resting-state) magnetic resonance imaging, salivary cortisol measurements, and self-report measures. Adolescents with pain and pain-free peers consistently recalled being more afraid of safety cues (CS-) and, during heightened stress at encoding (higher cortisol levels), also reported being more afraid of threat cues (CS+). However, no memory bias was present for the emotional response to an aversive stimulus (US; loud scream) or for the recall of pain intensity. Functional connectivity of the amygdala and hippocampus with memory circuits related to the degree of memory bias, but the specific connections varied between the studies, and we observed no relationship between memory bias and brain morphology. Our findings highlight the value of considering the interaction between implicit and explicit memory systems, contributing to a more comprehensive understanding of emotional memory biases in the context of chronic pain.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036612","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 : 2024-08-21DOI: 10.1097/j.pain.0000000000003381
Dana Rubenstein, Michael J Green, Maggie M Sweitzer, Francis J Keefe, F Joseph McClernon
Abstract: One-fifth of US adults experience chronic pain, which is associated with increased tobacco and cannabis use. Although bidirectional relationships between tobacco and pain have been demonstrated, pathways between pain, cannabis use, and co-use of cannabis and tobacco are understudied. We aimed to estimate the effects of (1) substance use (exclusive and co-use of cannabis and tobacco) on later pain intensity, and (2) pain intensity on later substance use. Data were from 31,983 adults in biennial surveys (2015-2021) of the US nationally representative longitudinal Population Assessment of Tobacco and Health Study (n = 71,055 pairs of consecutive surveys; T1 and T2). Past-week pain intensity was dichotomized (≤4/10 no/low pain; >4/10 moderate/severe pain). Mutually exclusive substance use categories (past 30 days) were no cannabis/tobacco use; exclusive cannabis/tobacco use; and co-use. Logistic regression assessed whether T1 substance use affected moderate/severe pain at T2. Multinomial models assessed whether pain status at T1 affected substance use at T2. Compared with no cannabis/tobacco use at T1, co-use (OR: 2.29 [95% CI: 2.09-2.51]), exclusive tobacco use (2.00 [1.86-2.14]), and exclusive cannabis use (1.35 [1.13-1.61]) were all associated with moderate/severe pain at T2. Moderate/severe pain at T1 increased odds of co-use (2.43 [2.22-2.66]), exclusive tobacco (2.12 [1.98-2.28]), and exclusive cannabis use (1.46 [1.29-1.65]) compared with no cannabis/tobacco use at T2, and increased odds of co-use at T2 compared with exclusive cannabis/tobacco use. Findings demonstrated bidirectional relationships between pain and the exclusive use and co-use of cannabis and tobacco and indicate potential synergy in the co-use of cannabis and tobacco with respect to pain.
{"title":"Bidirectional relationships between pain and patterns of cannabis and tobacco use in a US nationally representative sample.","authors":"Dana Rubenstein, Michael J Green, Maggie M Sweitzer, Francis J Keefe, F Joseph McClernon","doi":"10.1097/j.pain.0000000000003381","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003381","url":null,"abstract":"<p><strong>Abstract: </strong>One-fifth of US adults experience chronic pain, which is associated with increased tobacco and cannabis use. Although bidirectional relationships between tobacco and pain have been demonstrated, pathways between pain, cannabis use, and co-use of cannabis and tobacco are understudied. We aimed to estimate the effects of (1) substance use (exclusive and co-use of cannabis and tobacco) on later pain intensity, and (2) pain intensity on later substance use. Data were from 31,983 adults in biennial surveys (2015-2021) of the US nationally representative longitudinal Population Assessment of Tobacco and Health Study (n = 71,055 pairs of consecutive surveys; T1 and T2). Past-week pain intensity was dichotomized (≤4/10 no/low pain; >4/10 moderate/severe pain). Mutually exclusive substance use categories (past 30 days) were no cannabis/tobacco use; exclusive cannabis/tobacco use; and co-use. Logistic regression assessed whether T1 substance use affected moderate/severe pain at T2. Multinomial models assessed whether pain status at T1 affected substance use at T2. Compared with no cannabis/tobacco use at T1, co-use (OR: 2.29 [95% CI: 2.09-2.51]), exclusive tobacco use (2.00 [1.86-2.14]), and exclusive cannabis use (1.35 [1.13-1.61]) were all associated with moderate/severe pain at T2. Moderate/severe pain at T1 increased odds of co-use (2.43 [2.22-2.66]), exclusive tobacco (2.12 [1.98-2.28]), and exclusive cannabis use (1.46 [1.29-1.65]) compared with no cannabis/tobacco use at T2, and increased odds of co-use at T2 compared with exclusive cannabis/tobacco use. Findings demonstrated bidirectional relationships between pain and the exclusive use and co-use of cannabis and tobacco and indicate potential synergy in the co-use of cannabis and tobacco with respect to pain.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036611","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 : 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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036614","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 : 2024-08-20DOI: 10.1097/j.pain.0000000000003351
Nicola Neumann, Martin Domin, Martin Lotze
Abstract: This study set out to investigate in a population-based longitudinal cohort, whether chronification of back pain (BP) is related to structural gray matter changes in corticolimbic brain structures. Gray matter volume (GMV) was measured in participants with chronic BP (CBP, n = 168) and controls without chronic pain (n = 323) at 2 time points with an interval of 7 years (baseline t1, follow-up t2). Over this time period, participants with CBP showed an increase of GMV in the left ventral striatum, whereas controls showed a decrease. By contrast, participants with CBP had a GMV decrease in the left parahippocampal gyrus. Within the CBP group, pain duration was negatively associated with GMV in the left caudate. Those with emerging CBP had less GMV in the right entorhinal area, right amygdala, and left medial frontal cortex. Additional variables differing between those who had BP at t1 and later developed CBP or not were pain intensity, body mass index, and depression score. In sum, these findings are in accordance with the notion that limbic brain properties are both predisposing risk factors and drivers of brain reorganization during the development of CBP.
{"title":"Gray matter volume of limbic brain structures during the development of chronic back pain: a longitudinal cohort study.","authors":"Nicola Neumann, Martin Domin, Martin Lotze","doi":"10.1097/j.pain.0000000000003351","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003351","url":null,"abstract":"<p><strong>Abstract: </strong>This study set out to investigate in a population-based longitudinal cohort, whether chronification of back pain (BP) is related to structural gray matter changes in corticolimbic brain structures. Gray matter volume (GMV) was measured in participants with chronic BP (CBP, n = 168) and controls without chronic pain (n = 323) at 2 time points with an interval of 7 years (baseline t1, follow-up t2). Over this time period, participants with CBP showed an increase of GMV in the left ventral striatum, whereas controls showed a decrease. By contrast, participants with CBP had a GMV decrease in the left parahippocampal gyrus. Within the CBP group, pain duration was negatively associated with GMV in the left caudate. Those with emerging CBP had less GMV in the right entorhinal area, right amygdala, and left medial frontal cortex. Additional variables differing between those who had BP at t1 and later developed CBP or not were pain intensity, body mass index, and depression score. In sum, these findings are in accordance with the notion that limbic brain properties are both predisposing risk factors and drivers of brain reorganization during the development of CBP.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018234","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}
Abstract: Although the behavioral response to pain is complex and involves supraspinal processes, assessment of pain symptoms in animal models still mainly relies on reflex-based nociceptive tests, which do not account for the affective-motivational nor cognitive components of pain. We introduce a double avoidance place preference paradigm, an integrated testing procedure in freely moving rats that relies on the conflict between the avoidance of a dark compartment in which a thermal ramp is activated, and the escape towards an aversive brightly lit compartment. We were able to differentiate the first nociceptive threshold from the temperature of definitive escape from the dark compartment, conveying information on the adaptive behavior of animals. Measures were repeated after an hour to evaluate the adaptive learning response upon reexposure. In naive animals, there was a significant decrease in the time spent in the dark compartment at all stages of the testing paradigm upon reexposure, leading to a final escape before the flood had reached nociceptive values. This adaptive behavior was blunted by anxiolytic treatment. In animals exhibiting hyperalgesia following intraplantar complete Freund adjuvant injection, escape thresholds were significantly higher than that of control animals, hinting at a maladaptive affective-motivational response to noxious stimulation. However, in cuff animals, we failed to reveal any hot nociceptive hypersensitivity, but animals exhibited a strong adaptive response to cold simulation upon reexposure. Overall, the proposed paradigm allows for an integrated cortical response leading to a proactive avoidance behavior, while fully complying with ethical standards in animal experimentation.
{"title":"Between Scylla and Charybdis: assessing the multidimensional aspects of pain behaviors in rats using a double avoidance place preference paradigm.","authors":"Clémence Gieré, Andréa Thevenot, Yannick Menger, Géraldine Gazzo, Pierrick Poisbeau","doi":"10.1097/j.pain.0000000000003383","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003383","url":null,"abstract":"<p><strong>Abstract: </strong>Although the behavioral response to pain is complex and involves supraspinal processes, assessment of pain symptoms in animal models still mainly relies on reflex-based nociceptive tests, which do not account for the affective-motivational nor cognitive components of pain. We introduce a double avoidance place preference paradigm, an integrated testing procedure in freely moving rats that relies on the conflict between the avoidance of a dark compartment in which a thermal ramp is activated, and the escape towards an aversive brightly lit compartment. We were able to differentiate the first nociceptive threshold from the temperature of definitive escape from the dark compartment, conveying information on the adaptive behavior of animals. Measures were repeated after an hour to evaluate the adaptive learning response upon reexposure. In naive animals, there was a significant decrease in the time spent in the dark compartment at all stages of the testing paradigm upon reexposure, leading to a final escape before the flood had reached nociceptive values. This adaptive behavior was blunted by anxiolytic treatment. In animals exhibiting hyperalgesia following intraplantar complete Freund adjuvant injection, escape thresholds were significantly higher than that of control animals, hinting at a maladaptive affective-motivational response to noxious stimulation. However, in cuff animals, we failed to reveal any hot nociceptive hypersensitivity, but animals exhibited a strong adaptive response to cold simulation upon reexposure. Overall, the proposed paradigm allows for an integrated cortical response leading to a proactive avoidance behavior, while fully complying with ethical standards in animal experimentation.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018231","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 : 2024-08-15DOI: 10.1097/j.pain.0000000000003321
Andrew H Cooper, Allison M Barry, Paschalina Chrysostomidou, Romane Lolignier, Jinyi Wang, Magdalena Redondo Canales, Heather F Titterton, David L Bennett, Greg A Weir
Abstract: There is a rich literature describing the loss of dorsal root ganglion (DRG) neurons following peripheral axotomy, but the vulnerability of discrete subpopulations has not yet been characterised. Furthermore, the extent or even presence of neuron loss following injury has recently been challenged. In this study, we have used a range of transgenic recombinase driver mouse lines to genetically label molecularly defined subpopulations of DRG neurons and track their survival following traumatic nerve injury. We find that spared nerve injury leads to a marked loss of cells containing DRG volume and a concomitant loss of small-diameter DRG neurons. Neuron loss occurs unequally across subpopulations and is particularly prevalent in nonpeptidergic nociceptors, marked by expression of Mrgprd. We show that this subpopulation is almost entirely lost following spared nerve injury and severely depleted (by roughly 50%) following sciatic nerve crush. Finally, we used an in vitro model of DRG neuron survival to demonstrate that nonpeptidergic nociceptor loss is likely dependent on the absence of neurotrophic support. Together, these results profile the extent to which DRG neuron subpopulations can survive axotomy, with implications for our understanding of nerve injury-induced plasticity and pain.
{"title":"Peripheral nerve injury results in a biased loss of sensory neuron subpopulations.","authors":"Andrew H Cooper, Allison M Barry, Paschalina Chrysostomidou, Romane Lolignier, Jinyi Wang, Magdalena Redondo Canales, Heather F Titterton, David L Bennett, Greg A Weir","doi":"10.1097/j.pain.0000000000003321","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003321","url":null,"abstract":"<p><strong>Abstract: </strong>There is a rich literature describing the loss of dorsal root ganglion (DRG) neurons following peripheral axotomy, but the vulnerability of discrete subpopulations has not yet been characterised. Furthermore, the extent or even presence of neuron loss following injury has recently been challenged. In this study, we have used a range of transgenic recombinase driver mouse lines to genetically label molecularly defined subpopulations of DRG neurons and track their survival following traumatic nerve injury. We find that spared nerve injury leads to a marked loss of cells containing DRG volume and a concomitant loss of small-diameter DRG neurons. Neuron loss occurs unequally across subpopulations and is particularly prevalent in nonpeptidergic nociceptors, marked by expression of Mrgprd. We show that this subpopulation is almost entirely lost following spared nerve injury and severely depleted (by roughly 50%) following sciatic nerve crush. Finally, we used an in vitro model of DRG neuron survival to demonstrate that nonpeptidergic nociceptor loss is likely dependent on the absence of neurotrophic support. Together, these results profile the extent to which DRG neuron subpopulations can survive axotomy, with implications for our understanding of nerve injury-induced plasticity and pain.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000523","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}