Journal of Pain最新文献

{"title":"How to experimentally induce fear of movement-related pain and measure psychophysiological and behavioral reactions as a proxy – A scoping review","authors":"Larissa Pagels ,&nbsp;Ann Meulders ,&nbsp;Tibor M. Szikszay ,&nbsp;Waclaw M. Adamczyk ,&nbsp;Marvin Barnekow ,&nbsp;Kerstin Luedtke","doi":"10.1016/j.jpain.2025.105410","DOIUrl":"10.1016/j.jpain.2025.105410","url":null,"abstract":"<div><div>Fear can significantly increase the experienced pain intensity in individuals with chronic musculoskeletal pain and limit their ability to engage in daily activities. Fear of movement-related pain (FMRP) is commonly assessed via self-report, but research suggests measuring psychophysiological or behavioral parameters as an alternative. The objective of this scoping review was to identify and evaluate existing paradigms to induce FMRP, as well as the psychophysiological, behavioral and neural measurements used for its assessment. Experimental studies, with adult participants (≥18 years, healthy and chronic pain) observing or performing movements, were included if they used a FMRP induction paradigm or measured psychophysiological and behavioral proxies of FMRP. A total of 1883 studies were screened; 34 eligible studies were included. Paradigms inducing FMRP involved anticipated pain paired with movement (via classical or operant conditioning) or elicited pre-existing FMRP through the observation of movements potentially associated with pain. The identified studies employed various psychophysiological and behavioral measures indicating FMRP, such as response latency/duration, decision-making behavior, eyeblink startle response, and autonomic nervous system responses (e.g., skin conductance, heart rate, respiratory rate), as well as neural correlates (fMRI). fMRI studies revealed activation in fear- and pain-processing brain areas that correlated with patient-reported measurements (e.g., amygdala, hippocampus, lateral orbitofrontal cortex). Among the psychophysiological and behavioral measures displaying significant differences between fear-evoking, and neutral conditions, heart rate, respiratory response, skin conductance, and eyeblink-startle response demonstrated the largest effect sizes. In conclusion, physiological reactions can be measured during imagined, observed, or performed movements as a proxy for FMRP.</div></div><div><h3>Perspective</h3><div>This review provides an overview of existing paradigms to induce or elicit already conditioned FMRP in participants with chronic pain and in healthy participants. Therefore, the results of this review can inform future research projects that aim to further analyze the learning mechanisms behind and the processing of FMRP at brain level. Furthermore, measuring psychophysiological or behavioral proxies of FMRP can be beneficial not only in research settings, but also in clinical settings, to complement patient-reported outcome measures or to measure the FMRP of people with communicating issues, that are not able to complete a self-reported questionnaire.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"32 ","pages":"Article 105410"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Letter to the Editor: Future research directions on neuroplasticity in manual therapy and exercise for chronic neck pain","authors":"Rungtawan Chaikla ,&nbsp;Munlika Sremakaew ,&nbsp;Suwit Saekho ,&nbsp;Suchart Kothan ,&nbsp;Sureeporn Uthaikhup","doi":"10.1016/j.jpain.2025.105444","DOIUrl":"10.1016/j.jpain.2025.105444","url":null,"abstract":"","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"32 ","pages":"Article 105444"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain phenotype trajectories and links to family relationship quality among black older adults","authors":"Sarah B. Woods PhD ,&nbsp;Patricia N.E. Roberson PhD ,&nbsp;Bhaskar Thakur PhD ,&nbsp;Zureyat Sola-Odeseye BS ,&nbsp;Victoria Udezi MD, MPH ,&nbsp;Beatrice Wood PhD ,&nbsp;Staja Booker PhD, RN, FAAN","doi":"10.1016/j.jpain.2025.105484","DOIUrl":"10.1016/j.jpain.2025.105484","url":null,"abstract":"<div><div>Given persistent pain disparities experienced by older Black adults, understanding associations between family relationships and how chronic pain unfolds during aging has important clinical implications. This study aims to identify distinct longitudinal pain phenotype trajectories and whether these are associated with family relationship quality among older Black Americans. We included Black participants (<em>N</em>=2586; 64% women; mean age=66.65) from eight biennial waves (2006–2020) of the nationally representative Health and Retirement Study who reported on pain incidence at baseline. Latent class analyses (LCA) of pain incidence, severity, interference, and prescription pain medication use identified three cross-sectional pain phenotypes, consistently, at each wave: no pain; mild-to-moderate chronic pain; and severe high-impact chronic pain. Second-order LCA determined each participant’s probability of experiencing each pain phenotype at each wave, simultaneously, and identified five 14-year pain phenotype trajectories: No Chronic Pain; Persistent Mild-to-Moderate Chronic Pain; Persistent Severe High-Impact Chronic Pain; Chronic Pain Recovery; Chronic Pain Worsening. Compared to pain-free adults, the odds of persistent mild-to-moderate pain were lower with greater intimate partner support and higher with greater intimate partner strain. The odds of persistent severe high-impact chronic pain were lower with greater intimate partner, family, and parent-child support, each, and higher with greater family and parent-child strain. Greater parent-child strain was also linked to higher odds of pain worsening over time. Ameliorating strained relationships and leveraging supportive relationship benefits may provide a culturally-attuned biopsychosocial approach to improving older Black Americans’ pain. Research is needed to determine mediating mechanisms for identification of precise intervention targets.</div></div><div><h3>Perspective</h3><div>This article describes trajectories of pain phenotypes (clusters of distinct pain indicators) for older Black Americans. Identified links between supportive and strained family relationships and ways in which aging Black adults’ pain unfolds over time may provide apt intervention targets in biopsychosocial pain management approaches.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"34 ","pages":"Article 105484"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synchronal dual brain stimulation over the somatosensory cortex modulated social touch-induced analgesia depending on empathy.","authors":"Naoyuki Takeuchi, Yoshino Terui","doi":"10.1016/j.jpain.2025.105483","DOIUrl":"10.1016/j.jpain.2025.105483","url":null,"abstract":"<p><p>Social touch, when provided as emotional support, can induce pain relief. Alpha inter-brain synchrony in the somatosensory cortex may be a neural factor contributing to the pain relief induced by social touch. This study investigated whether artificial manipulation of inter-brain communication in the pain-receiver and touch-giver could modulate touch-induced analgesia using transcranial alternating current stimulation. Sixteen same-sex pairs of participants were assigned the roles of pain-receiver and touch-giver during alpha-band transcranial alternating current stimulation applied to the somatosensory cortex. Three transcranial alternating current stimulation conditions were randomized, and the participant roles changed between sessions: (1) the pain-receiver received transcranial alternating current stimulation and the touch-giver received sham stimulation; (2) both received transcranial alternating current stimulation (hyper-transcranial alternating current stimulation); and (3) both received sham stimulation. Social touch reduced pain, although there were no significant differences in pain perception among the three conditions. Analgesia by social touch during hyper-transcranial alternating current stimulation, compared with sham transcranial alternating current stimulation, was negatively correlated with the empathy level of the pain-receiver. No relationship was observed between pain relief and empathy levels when transcranial alternating current stimulation was administered only to the pain-receiver. Hyper-transcranial alternating current stimulation aimed to enhance alpha-band synchrony between dyads could promote touch-induced analgesia, especially in pain-receivers with low emotional empathy. These findings indicate a possible association between synchrony of somatosensory alpha activity and pain relief through social interactions. Manipulating brain synchrony by considering a patient's empathy level may support therapeutic analgesia influenced by the clinician-patient relationship. PERSPECTIVE: This study provides preliminary evidence for a possible association between alpha inter-brain synchrony in the somatosensory cortex and touch-induced analgesia from temporarily altering brain oscillations using hyper-transcranial alternating current stimulation. Manipulating inter-brain synchrony while considering a patient's empathy level may enhance therapeutic analgesia influenced by the clinician-patient relationship.</p>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":" ","pages":"105483"},"PeriodicalIF":4.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do health outcomes following pain service utilization vary for young people experiencing chronic pain according to pain phenotype? An exploratory analysis using the electronic Persistent Pain Outcomes Collaboration database.","authors":"Robert Waller, Helen Slater, Andrew M Briggs, Susan M Lord, Anne J Smith","doi":"10.1016/j.jpain.2025.105482","DOIUrl":"https://doi.org/10.1016/j.jpain.2025.105482","url":null,"abstract":"<p><p>The prevalence of chronic pain in young people increases with age, approaching rates observed in adults. Utilizing Australiasian electronic Persistent Pain Outcomes Collaboration (ePPOC) data for young people, we previously derived three phenotypes (\"low\", \"moderate\", \"high\") characterized by an increasing symptom-severity gradient in multi-dimensional pain-related variables measured at referral to pain service. In this study, we explored whether health outcomes varied by phenotypes at the end of care episode. We included young people captured in the Australian adult ePPOC data registry representing 80 tertiary and private pain services, within a 5-year period (2018 to 2022) if previously phenotyped and had episode end patient reported outcome measures. Self-reported global rating of change was measured at episode end, while pain severity and interference, pain-related worry (quasisurrogate 'catastrophizing'), emotional functioning and pain self-efficacy were measured at referral and episode end. Differences in outcomes across phenotypes were estimated using logistic regression for binary indicators and clinically significant improvements, and linear regression for mean change. Of 3518 young people initially phenotyped from adult service data, 477 (13.6%) aged 15-25 years had episode end outcomes. The proportion of participants reporting meaningful improvement in outcomes ranged from 24.0%-74.2%, with differences observed across phenotypes. Although the limited proportion of participants with episode end data may have introduced bias, those with and without end episode outcomes were broadly comparable on baseline demographics. Results suggests tailoring care to symptom-severity may be important for optimising outcomes, particularly for young people with \"high\" symptom-severity whose care needs are more complex. PERSPECTIVE: This study reports unique exploration of whether the outcomes following specialized pain service care supporting young people living with chronic pain varied according to their symptom-severity phenotype. This evidence provides impetus for system and service improvements to more equitably and efficiently meet young people's needs by providing timely, differential care.</p>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":" ","pages":"105482"},"PeriodicalIF":4.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-wave study on intrapersonal stigma, social isolation, well-being, and functioning in individuals with chronic pain: A structural equation modeling approach.","authors":"Van Alboom Maité, F Bernardes Sónia, Baert Fleur, Bracke Piet, Goubert Liesbet","doi":"10.1016/j.jpain.2025.105479","DOIUrl":"https://doi.org/10.1016/j.jpain.2025.105479","url":null,"abstract":"<p><p>Stigmatization poses significant challenges for individuals living with chronic pain (CP), particularly when pain complaints lack a clear pathophysiological basis, referred to as primary CP. Although the negative impact of stigmatization on well-being and functioning of individuals with CP is acknowledged, its systematic and theory-driven investigations are sparse. Moreover, the underlying mechanisms linking CP stigmatization to adverse outcomes have yet to be examined. This study conducted an online, two-wave prospective questionnaire, collecting data from 332 individuals with chronic pain in the first wave (271 women, M age = 50y) and a subset of the same sample (N= 295; 241 women, M age = 54y) in the second wave (1 year later). Structural equation modeling revealed several key findings: (1) Individuals with primary CP perceived higher intrapersonal stigma compared to those with secondary CP. (2) Higher perceived stigma was related to increased mental distress and to decreased functioning/participation, both via higher levels of social isolation. 3) The structural relationships were not statistically equivalent across primary and secondary CP, suggesting moderation. 4) Finally, changes in perceived stigma were related to changes in functioning/participation in daily life and changes in mental distress, but only the model with mental distress was mediated by changes in social isolation. The findings underscore the importance of addressing perceived stigma and social isolation to improve mental health outcomes in CP patients. Clinically, tailored interventions that consider the unique needs of patients with primary versus secondary CP are necessary. PERSPECTIVE: This paper presents results of a two-wave questionnaire study on perceived stigma, social isolation, well-being, and functioning. The role of chronic pain type, namely primary versus secondary chronic pain is being examined.</p>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":" ","pages":"105479"},"PeriodicalIF":4.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eight-year chronic pain trajectory and risk of cardiovascular disease: Evidence from 10 years of multicenter follow-up","authors":"Xiongda Yao M.D. ,&nbsp;Yurong Leng M.D. ,&nbsp;Junda Cao M.D. ,&nbsp;Miao Yu M.D. ,&nbsp;Yue Zhou M.D.","doi":"10.1016/j.jpain.2025.105478","DOIUrl":"10.1016/j.jpain.2025.105478","url":null,"abstract":"<div><div>Previous studies have shown that chronic pain is associated with an increased risk of cardiovascular disease. However, there are no studies reporting the relationship between chronic pain trajectories and cardiovascular disease. The pooled data from two prospective cohorts, the Health Retirement Study (HRS) and the English Longitudinal Study of Ageing (ELSA), were included in this study, and five chronic pain trajectories were established based on eight years of follow-up. Cox proportional risk regression models were used to assess the association between different chronic pain trajectories and cardiovascular disease. A total of 19,234 participants were included in the study and were followed for 10 years. With the no pain trajectory as the reference group, increasing pain (HR:1.41, 95% CI: 1.24–1.61) and consistent pain (HR:1.27, 95% CI:1.14–1.43) trajectories were all significantly associated with an increased risk of cardiovascular disease. Conversely, the decreasing pain (HR:1.04, 95% CI:0.90–1.21) and fluctuating (HR:1.02, 95% CI:0.95–1.10) trajectory was not significantly associated with cardiovascular disease. However, no significant association was observed between chronic pain trajectories and stroke risk. The present study demonstrates that both increasing and consistent pain trajectories are significantly associated with an elevated risk of cardiovascular disease. In contrast, decreasing pain trajectories were not associated with cardiovascular risk. Therefore, incorporating chronic pain assessment into cardiovascular disease management is warranted.</div></div><div><h3>Perspective</h3><div>This longitudinal study highlights the importance of chronic pain trajectories in predicting cardiovascular disease. Findings support the integration of long-term pain patterns into cardiovascular risk assessments to improve prevention and management strategies.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"34 ","pages":"Article 105478"},"PeriodicalIF":4.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opposing effects of mu opioid receptors on dopamine D1 and D2 receptor expressing neurons in opioid mediated antinociception.","authors":"Jacob Alderete, Anthony Tanzillo, Jason Miller, Lorna Barrall, Hazem Nasef, Emily Ellis, Gabriella Sigal, Flora D'Oliveira Da Silva, Merel Dagher, Christopher J Evans, Catherine M Cahill","doi":"10.1016/j.jpain.2025.105474","DOIUrl":"https://doi.org/10.1016/j.jpain.2025.105474","url":null,"abstract":"<p><p>There is extensive interaction between systems involved in pain processing and motivation, where the aberrant functioning of salience circuits likely contributes to chronic pain, as well as increased susceptibility to opioid misuse and opioid use disorder. This study asks to what extent mu opioid receptors (MORs) in dopamine D1 receptor (D1R), D2 receptor (D2R) or adenosine A2a receptor (A2aR) expressing neurons contribute to the expression of pain and opioid antinociception. We ablated MORs in dopamine receptor expressing neurons by breeding D1R, D2R or A2aR-cre with MOR^loxP mice, which was confirmed by RNAscope multiplex fluorescent in situ hybridization. To determine the role of these MORs in nociception, we assessed the nociceptive responses in the hot plate and formalin tests with and without treatment with oxycodone (3 mg/kg, i.p.). Pain-like behavior in a thermal assay, mechanical thresholds following nerve injury, and the formalin test were not altered by genotype. However, oxycodone-induced antinociception in the formalin test was differentially altered. Opioid antinociception was attenuated in mice that lacked MORs in D1R neurons, but was enhanced when MORs were ablated in either the D2R and A2aR neurons. In contrast, there was no effect of genotype on oxycodone-induced antinociception in the thermal nociceptive test. Together, these data show that MORs in D1R expressing neurons is necessary for opioid-induced antinociception in a model of tonic inflammatory pain, but not acute thermal pain. Whereas, MOR in D2R and A2aR expressing neurons had a tonic inhibitory tone on opioid-mediated antinociception in the formalin test. PERSPECTIVE: This article presents evidence that mu opioid receptors in dopamine receptor containing neurons differentially modulate opioid antinociception in the formalin test but not threshold evoked phasic pain. The endogenous opioid system in these neuronal populations does not appear to modulate various pain behaviors.</p>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":" ","pages":"105474"},"PeriodicalIF":4.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal white matter microstructure in the amygdala-related fiber tract pathways in patients with trigeminal neuralgia: A multivariate analysis","authors":"Chuan Zhang ,&nbsp;Baijintao Sun ,&nbsp;Tingdan Deng ,&nbsp;Wei Zhang ,&nbsp;Hongjian Li ,&nbsp;Ruhui Xiao ,&nbsp;Bing Li ,&nbsp;Xiaoxue Xu ,&nbsp;Jixin Liu ,&nbsp;Hanfeng Yang","doi":"10.1016/j.jpain.2025.105480","DOIUrl":"10.1016/j.jpain.2025.105480","url":null,"abstract":"<div><div>Trigeminal neuralgia (TN) is characterized by recurrent, severe facial pain often accompanied by negative emotional states such as anxiety and depression. However, the neurobiological mechanisms linking pain and emotion in TN remain unclear. In this cross-sectional study, we used diffusion tensor imaging (DTI) with seed-based fiber streamline analysis to examine amygdala-related white matter pathways in 46 TN patients and 35 age- and sex-matched healthy controls. Pain was quantified using the Penn Facial Pain Rating (PFPR) and the McGill Pain Questionnaire (MPQ), while emotional distress was assessed via the Pain Catastrophizing Scale (PCS) and the Pain Anxiety Symptom Scale (PASS). Compared with controls, TN patients exhibited significantly lower fractional anisotropy (FA) values (p &lt; 0.05) and higher mean diffusivity in these fiber tracts, mainly located at the splenium of the corpus callosum, bilateral anterior corona radiata, and bilateral external capsule. Correlation analysis revealed that higher PCS scores were significantly associated with increased PFPR scores (r = 0.56, p &lt; 0.001). Furthermore, mediation analysis demonstrated that abnormal FA in the amygdala-related fiber pathways partially mediated the relationship between negative emotions and facial pain intensity (direct effect: b = 0.475, p &lt; 0.001; indirect effect: b = 0.084, p = 0.008). These results suggest that alterations in amygdala-related white matter microstructure may underlie the interplay between negative emotions and pain in TN, providing a potential neurobiological basis for future targeted interventions.</div></div><div><h3>Perspective</h3><div>This study suggests that pain catastrophizing may alter brain structure and contribute to chronic facial pain in trigeminal neuralgia patients. Early interventions targeting negative emotions could prevent further structural changes and improve clinical outcomes.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"34 ","pages":"Article 105480"},"PeriodicalIF":4.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced functional resting-state connectivity in chronic pain patients with small fiber neuropathy.","authors":"Sebastian Scheliga, Han-Gue Jo, Maike F Dohrn, Thilo Kellermann, Angelika Lampert, Roman Rolke, Greta Z Peschke, Noortje W M van den Braak, Annette Lischka, Robin Bekrater-Bodmann, Ute Habel","doi":"10.1016/j.jpain.2025.105477","DOIUrl":"https://doi.org/10.1016/j.jpain.2025.105477","url":null,"abstract":"<p><p>Chronic neuropathic pain can lead to structural and functional brain reorganization. Neuropathic pain, the main symptom of small fiber neuropathy (SFN), may be linked to specific brain biosignatures. Functional connectivity changes during resting state (RS) have been observed in SFN patients, but little is known about these changes in idiopathic SFN. To explore this, we conducted RS-fMRI in 32 idiopathic SFN patients and 31 healthy controls (HC), focusing on the bilateral caudate nucleus (CN), where reduced gray matter volume (GMV) was previously reported. Functional connectivity analysis revealed that SFN patients had decreased connectivity between the right CN and the left supplementary motor area (SMA) compared to HC. This reduced connectivity correlated positively with both the patients' total pain score (painDETECT) and the GMV of both caudate nuclei, suggesting that decreased RS connectivity is associated with lower GMV and higher pain levels. Exploratory subgroup analyses in patients with rare heterozygous missense variants in voltage-gated sodium channels (Nav) showed distinct connectivity patterns, highlighting potential genetic influences. Our findings suggest that brain functional changes during RS may be linked to a structural basis in chronic pain and might serve as neural signature for SFN patients. Further studies are needed to confirm these results and to investigate the role of genetic factors in SFN-related brain changes.</p>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":" ","pages":"105477"},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}