European Journal of Pain最新文献

{"title":"Postoperative Pain Treatment After Pancreatic Surgery: A Systematic Review With Meta-Analyses and Trial Sequential Analyses","authors":"Caroline D. Lassen, Fatieh Yousef, Eske Kvanner Aasvang, Waqas Farooqui, Sermed Ellebæk Nicolae, Anja Geisler","doi":"10.1002/ejp.70428","DOIUrl":"https://doi.org/10.1002/ejp.70428","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Major pancreatic surgery is associated with significant postoperative pain that impairs early mobilisation and recovery. ERAS guidelines for pancreaticoduodenectomy recommend multimodal opioid-sparing analgesia, with a strong recommendation for epidural analgesia and continuous wound infiltration as an alternative. Other techniques may be beneficial, but their efficacy and safety remain uncertain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the efficacy and adverse events of different postoperative analgesic modalities for patients undergoing total pancreatectomy, pancreaticoduodenectomy and distal pancreatectomy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Databases and Data Treatment</h3>\u0000 \u0000 <p>This PROSPERO-registered systematic review (ID CRD420251085003) reported in accordance with the PRISMA guidelines. A search for randomised controlled trials was conducted in Medline, Cochrane Central Register of Controlled Trials and Embase. Meta-analyses were performed in Review Manger, risk of bias was assessed with RoB 2, trial sequential analyses were performed, and the certainty of evidence was evaluated using GRADE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighteen RCTs comprising 1468 patients were included, and 10 meta-analyses were performed. Meta-analyses demonstrated reduced pain scores at rest on postoperative day (POD) two with COX-inhibitors compared with placebo/no intervention. Pain scores were similar when comparing epidural analgesia with less invasive strategies (paravertebral block and wound infiltration) on POD1–POD2, but lower with the less invasive techniques on POD3. Meta-analyses were small, and GRADE recommendations ranged from very low to low.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The available evidence was insufficient to establish the superiority of any single analgesic strategy after major pancreatic surgery. Several analgesic strategies, including COX inhibitors, paravertebral block and continuous wound infiltration, showed promising results. Larger RCTs are needed to provide stronger evidence-based recommendations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Epidural analgesia has long been considered the gold standard for treatment of postoperative pain after major pancreatic surgery. The present review adds to the field by demonstrating that less i","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejp.70428","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149259365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intact Conditioned Pain Modulation Despite Altered Pain Sensitivity in Migraine Across Phases and Sites","authors":"Tibor M. Szikszay, Jakob Poehlmann, Waclaw M. Adamczyk, Kerstin Luedtke, Gabriela F. Carvalho","doi":"10.1002/ejp.70433","DOIUrl":"https://doi.org/10.1002/ejp.70433","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Altered endogenous pain-inhibitory pathways have been proposed as a mechanistic contributor to migraine. However, results from conditioned pain modulation (CPM) paradigms are inconsistent, potentially reflecting limited assessment of trigeminal nociception and a paucity of data stratified by migraine phase. Accordingly, this study aimed to evaluate the site- and phase-dependence of CPM and somatosensory sensitivity in migraine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a cross-sectional study, 50 adults with migraine and 50 age-/sex- headache-free controls underwent assessor-blinded, standardized CPM and quantitative sensory testing (QST) at a trigeminal site (V1, forehead) and an extra-trigeminal site (C6, forearm). CPM was calculated as the change in heat pain thresholds measured during a heterotopic ischemic conditioning stimulus relative to baseline. QST captured thermal, pressure and mechanical pain measures, also including mechanical pain sensitivity and allodynia. Repeated-measures ANOVAs tested effects of CPM, site, diagnosis and migraine phase (peri-ictal vs. interictal).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A robust inhibitory CPM effect was observed in both migraine and control groups, with no between-group or phase-specific differences across sites (all <i>p</i> > 0.05). Compared with controls and not considering the stimulated region, migraine was associated with lower pressure pain thresholds (<i>p</i> < 0.001) and higher mechanical pain sensitivity (<i>p</i> = 0.001), alongside elevated central sensitization and catastrophizing scores (<i>p</i> < 0.001). Across migraine phases, pain sensitivity measures were largely stable; however, trigeminal mechanical pain sensitivity was selectively higher during the peri-ictal phase (<i>p</i> = 0.017).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CPM appears preserved in migraine across phases and anatomical territories, whereas sensory alterations may be modality- and region-specific, supporting a pain sensitivity amplification phenotype rather than a generalized deficit in endogenous inhibition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Patients with migraine could inhibit pain similarly to controls, but they present in general lower pressure and mechanical pain thresholds in contrast to controls and increased mechanical sensitivity on the forehead during the peri-ictal phase. This suggests that migraine involves specific changes in pain processing rather than a general disruption of the descending inhibitory","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149259490","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":"Expectations in Pain Research: Measured or Assumed?","authors":"Przemysław Bąbel","doi":"10.1002/ejp.70436","DOIUrl":"https://doi.org/10.1002/ejp.70436","url":null,"abstract":"<p>This journal recently published a paper by Lunde et al. (<span>2026</span>) entitled ‘To ask or not to ask: Does inquiring about participants' expectations influence the placebo effect? A placebo mechanism study in healthy volunteers’. The study addresses whether measuring expectations influences placebo analgesia.</p><p>In 64 healthy volunteers, placebo effects were numerically larger when participants rated expected pain before stimulation, but between-group differences were not statistically significant. As the authors acknowledge, the study was not powered to detect these differences or establish equivalence. The results therefore leave the question of measurement reactivity open and call for further evaluation of expectation assessment. The study is important because it also prompts two broader questions: what evidence establishes expectations as a mechanism, and what exactly do expectation measures capture?</p><p>Expectations are widely proposed as a principal mechanism of placebo and nocebo effects, and these effects are sometimes defined in terms of expectations. Yet their involvement is sometimes inferred without measurement. When verbal suggestion, classical conditioning, observational learning or their combination produces placebo hypoalgesia/analgesia or nocebo hyperalgesia, the outcome alone does not establish that expectations changed or caused the effect. Induction procedures and their mechanisms must be distinguished. Inferring expectation mediation from the occurrence of a placebo or nocebo effect treats a theoretical explanation as an empirical finding (Bąbel <span>2019</span>).</p><p>This problem also concerns the definition of expectations. In Kirsch's response expectancy theory, expectations concern anticipated nonvolitional reactions, such as pain (Trusz and Bąbel <span>2016</span>). These expectations are understood as consciously accessible and, in principle, reportable (Bąbel <span>2019</span>). Lunde et al.'s interviews are informative here: participants predominantly described expectations as thoughts or assumptions about future outcomes. Measuring expectations is therefore crucial for understanding their role.</p><p>Proposals that expectations can be unconscious or implicit require an explicit definition and evidence independent of the effect being explained. Inferring unreported expectations simply because pain changed makes the explanation circular (Bąbel <span>2019</span>). Neither missing expectation measures nor unsuccessful mediation analyses establish that implicit expectations produced the effect. Unconscious learning remains a possible explanation, but labelling it expectancy without independent evidence obscures distinctions between mechanisms. Conversely, a null association with reported expectations does not rule out their involvement; measurement sensitivity and statistical precision must be considered.</p><p>Expectations and pain should also be examined as separate outcomes. Learning procedures may cha","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejp.70436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149259339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Variations of Pressure Sensitivity Within and Between Chronic Painful Jaw Muscles—A Case–Control Clinical Study","authors":"Juan Fernando Oyarzo,&nbsp;Manolis Jusakos,&nbsp;Paula Zamora,&nbsp;Eduardo Castrillón,&nbsp;Fernando G. Exposto,&nbsp;Peter Svensson","doi":"10.1002/ejp.70423","DOIUrl":"https://doi.org/10.1002/ejp.70423","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Orofacial myofascial pain shows variable muscle sensitivity, referred pain, and complex spatiotemporal pressure processing profiles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This participant-, examiner- and data analyst-blinded case–control study compared masticatory muscle sensitivity and entropy patterns between 28 chronic myofascial TMD pain patients and 28 age- and sex-matched controls, introducing a comprehensive approach for ‘topoalgesia’ assessment. Mechanical pain sensitivity (MPS) was assessed at nine sites on the masseter and temporalis muscles bilaterally using a palpometer with 0.5, 1.0 and 2.0 kgf for 2 s. Participants rated MPS on a 0–50–100 numeric rating scale after each palpation and reported referred sensations. Entropy and center of gravity (COG) were analysed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Chronic myofascial TMD pain patients reported significantly greater MPS scores than controls across all force levels and muscles (<i>p</i> &lt; 0.05). Both groups showed increased MPS with higher applied forces. TMD patients exhibited significantly greater entropy in the masseter muscle at 0.5 and 1.0 kgf, and in the temporalis muscle at 2.0 kgf (<i>p</i> &lt; 0.001). TMD patients also reported more referred sensations than controls across all force levels (<i>p</i> &lt; 0.001). COG analysis showed myofascial TMD patients presented more centrally located COG within the masseter muscle than controls particularly at lower forces.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Results suggest that chronic myofascial TMD patients present greater muscle sensitivity, differing entropy profiles across muscles and force levels, and distinct spatiotemporal patterns compared to controls, associated with more frequent referred sensations. These findings contribute to understanding chronic muscle pain manifestations, and topoalgesia may help better track disease progression or remission over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Quantification of spatial variation in pressure sensitivity (topoalgesia) showed that chronic myofascial TMD patients diverge from healthy controls at 0.5 kg and 2.0 kg palpation forces, but not at 1.0 kg, identifying force-specific parameters that could sharpen diagnostic sensitivity for orofacial pain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149258976","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":"Unravelling Sleep-Pain Interactions: Methodological Advantages and Inflammation","authors":"Stefan Lautenbacher","doi":"10.1002/ejp.70438","DOIUrl":"https://doi.org/10.1002/ejp.70438","url":null,"abstract":"&lt;p&gt;This journal recently published a paper by the research group of Monika Haak entitled ‘Effects of low-dose acetylsalicylic acid on spontaneous pain, pain sensitivity, and central pain modulation in response to a sleep restriction challenge in healthy individuals’ (Nett et al. &lt;span&gt;2026&lt;/span&gt;). The study builds on the well-established bidirectional relationship between sleep disturbances and pain, in which each can exacerbate the other. The authors hypothesized that inflammatory processes may be key mediators of this relationship. In a randomized, double-blind crossover study, they investigated whether pre-emptive administration of low-dose acetylsalicylic acid (ASA; aspirin) could mitigate the pain-enhancing effects of sleep restriction in healthy adults. Sleep restriction involved five consecutive nights with only 4 h of sleep opportunity. Although 14 days of ASA administration did not affect baseline pain ratings, pain sensitivity, or pain modulation, it attenuated the increase in widespread and muscle pain associated with sleep restriction and reduced the impairment of endogenous pain inhibition compared with placebo. These findings suggest that inflammatory pathways may contribute to the effects of insufficient sleep on pain processing.&lt;/p&gt;&lt;p&gt;The merit of this study rests on two major achievements: (1) the methodological excellence of experimentally simulating everyday sleep disturbances through repeated sleep restriction and (2) the opportunity to not only investigate the relationship between disturbed sleep and pain but also to experimentally modify their pathological linkage, thereby gaining insights into the underlying mechanisms.&lt;/p&gt;&lt;p&gt;Natural variations in sleep among healthy individuals are not always sufficient to demonstrate reliable changes in the pain system. More pronounced effects can be observed when sleep is experimentally restricted or fragmented (Lautenbacher &lt;span&gt;2018&lt;/span&gt;). The research group of Monika Haak has developed excellent experimental designs and protocols with high ecological validity that produce sufficiently robust and reproducible effects on pain processing. The partial sleep restriction paradigm used in the present study was designed to reflect common patterns of insufficient sleep during the working week, followed by recovery sleep on weekends, as frequently observed in modern societies. Developing such ecologically valid paradigms is essential to model the transition from a at first relatively balanced pain system to one increasingly affected by initially subclinical and potentially later clinically relevant sleep disturbances (Simpson et al. &lt;span&gt;2018&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;The mechanisms underlying the relationship between sleep disturbances and pain remain largely unknown. One reason for that is the considerable time, effort, and resources required to design and conduct studies capable of identifying specific mechanisms. The present study illustrates these challenges, requiring substantial commitment fro","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejp.70438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149258079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specificity and Equivalence in Chronic Pain Psychological Therapy: We Need to Look Beyond Average Package Comparison","authors":"Sérgio A. Carvalho","doi":"10.1002/ejp.70437","DOIUrl":"https://doi.org/10.1002/ejp.70437","url":null,"abstract":"&lt;p&gt;This journal recently published a paper by Torrijos-Zarcero et al. (&lt;span&gt;2026&lt;/span&gt;), entitled ‘Shared and Differential Psychological Processes Associated with Treatment Response in Mindful Self-Compassion and Cognitive-Behavioral Therapy for Chronic Pain: An Exploratory Secondary Analysis of a Randomized Controlled Trial’. The authors revisit a valuable previously published head-to-head trial to ask whether changes in pain acceptance, catastrophizing, and self-compassion relate (dis)similarly to outcomes in mindful self-compassion (MSC) and cognitive-behavioural therapy (CBT). Their findings invite a broader question that cuts through psychological intervention research: what exactly do we mean when we call treatments equivalent or specific?&lt;/p&gt;&lt;p&gt;Similar average results across psychotherapies do not necessarily mean treatments work through identical processes, benefit the same individuals, or yield equivalent change across outcomes and time. Robust meta-analytic work underscores that established therapies help many, but not all, and, perhaps more importantly, that ‘new’ treatment labels have not reliably brought superior average outcomes (Cuijpers &lt;span&gt;2024&lt;/span&gt;). This evidence tempers assumptions that multiplying named packages will itself improve care. It also points to identifying what helps nonresponders and whether/how approaches differ across outcomes and recovery durability.&lt;/p&gt;&lt;p&gt;These questions matter especially in chronic pain, given its multi-level domains: sensory intensity, interference with activity, emotional distress, social participation, and pain-related expectations, meanings, and beliefs can change together, but need not do so. Therefore, an average comparison of treatment packages can conceal convergence at one level alongside divergence at another. A process may also be modified by both therapies yet differ in when or for whom it does. So, we argue that treatment (non)specificity is best framed as a comparative, conditional claim: which interventions engage which processes, for which individuals, in what contexts, and causally changing which outcomes?&lt;/p&gt;&lt;p&gt;Torrijos-Zarcero et al. (&lt;span&gt;2026&lt;/span&gt;) tentatively contribute to this clarification: MSC and CBT shared associations between changes in several candidate processes and clinical outcomes, but differed in patterns involving acceptance and helplessness. These results should not be read as showing that the therapies are interchangeable, or that either differing process is a causal therapeutic mechanism (processes and outcomes were measured only at baseline and post-treatment, thus the study cannot establish temporal order, that is, that change in processes precedes change in outcomes), but it is a valid effort in generating evidence-based hypotheses about treatment specificity. Given that acceptance/self-compassion and cognitive strategies are not exclusive to MSC and CBT, respectively, the relevant question is not which therapy ‘owns’ a process, but whether it","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejp.70437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149258078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Reorganization of Hypothalamic Subfields in Postherpetic Neuralgia: Volumetric and Morphometric Covariance Network Analyses","authors":"Daeseok Oh,&nbsp;Dong Ah Lee,&nbsp;Ho-Joon Lee,&nbsp;Kang Min Park","doi":"10.1002/ejp.70434","DOIUrl":"https://doi.org/10.1002/ejp.70434","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Postherpetic neuralgia (PHN) is a chronic neuropathic pain condition associated with central nervous system reorganization, but hypothalamic alterations remain poorly understood. We investigated hypothalamic subfield volumes and morphometric covariance network organization in patients with PHN.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This prospective cross-sectional study included 42 patients with PHN and 41 healthy controls whose hypothalamic subfield volumes were obtained from T1-weighted MRI using automated FreeSurfer segmentation. Bilateral mean raw subfield volumes were compared between groups using analysis of covariance, adjusting for age, sex and estimated total intracranial volume, with false discovery rate correction for multiple comparisons. Morphometric covariance networks were constructed from age- and sex-residualized subfield volumes and graph-theoretical measures were compared using permutation testing.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;After adjustment for estimated total intracranial volume, age and sex, the tubular superior subfield was nominally larger in PHN (adjusted difference, 4.95 mm&lt;sup&gt;3&lt;/sup&gt;; 95% CI, 0.05–9.85; &lt;i&gt;p&lt;/i&gt; = 0.048), but did not survive FDR correction. No other subfield or whole-hypothalamic volume differed significantly. PHN showed reduced local efficiency and clustering coefficient and increased characteristic path length, without a significant difference in global efficiency. No pain-side-dependent lateralization or significant associations between subfield volumes and pain measures or disease duration were observed.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;PHN was associated with altered hypothalamic morphometric covariance organization, characterized by reduced local network segregation and increased characteristic path length, while regional volume differences were limited after intracranial volume correction. These findings suggest that PHN-related central reorganization may involve hypothalamic systems related to homeostatic regulation and stress adaptation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance Statement&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study demonstrates altered morphometric covariance organization of hypothalamic subfields in postherpetic neuralgia, despite limited evidence of regional volumetric differences after intracranial volume adjustment. These findings suggest that hypothalamic involvement in PHN may be better reflected by altered coordinated structural organization than by regional volume changes alone.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 ","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222836","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 Andrea Truini: Diagnosing a Lesion or Diagnosing Neuropathic Pain?","authors":"Didier Bouhassira,&nbsp;Nadine Attal","doi":"10.1002/ejp.70435","DOIUrl":"https://doi.org/10.1002/ejp.70435","url":null,"abstract":"&lt;p&gt;We thank Professor Andrea Truini for his thoughtful and constructive commentary (Truini &lt;span&gt;2026&lt;/span&gt;) on our position paper related to the NeuPSIG diagnostic algorithm for neuropathic pain (Bouhassira and Attal &lt;span&gt;2026&lt;/span&gt;). We are pleased that we share substantial common ground: diagnostic confidence in neuropathic pain should emerge from the convergence of multiple sources of information rather than from a rigid hierarchy privileging supposedly objective findings over patients' reports. Our disagreement concerns a narrower but fundamental question: should investigations demonstrating a somatosensory lesion contribute directly to the classification of pain as neuropathic?&lt;/p&gt;&lt;p&gt;We entirely agree that ‘imperfect tests are not uninformative tests’. We never argued otherwise. Paraclinical investigations are clinically valuable and often essential for identifying an underlying neurological lesion or disease. Our proposal is to reconsider their role in pain classification, not to dismiss their clinical utility. The critical distinction concerns what these investigations really demonstrate. Nerve conduction abnormalities establish peripheral nerve dysfunction, reduced intraepidermal nerve fibre density indicates small-fibre pathology, and imaging may identify structural lesions. However, none establishes that the identified abnormality causes the patient's pain. This distinction matters because neurological lesions are frequently painless, and structural abnormalities may also occur in conditions not conventionally classified as neuropathic pain. Even a hypothetical test with perfect sensitivity and specificity for detecting a neurological lesion would not necessarily establish whether that specific lesion causes pain. Hence, accuracy for diagnosing a lesion and accuracy for classifying pain are fundamentally different purposes.&lt;/p&gt;&lt;p&gt;Adrea Truini refers to the studies by Peter Dyck and colleagues to support objective anchoring when clinical examination is unreliable. However, these studies evaluated the diagnosis of diabetic polyneuropathy, not whether patients' pain was neuropathic. Nerve conduction studies provide an excellent reference for diagnosing neuropathy, but do not constitute an equivalent reference for classifying pain. The same reasoning applies to small-fibre neuropathy. Diagnostic criteria combining clinical signs, thermal thresholds and intraepidermal nerve fibre density illustrate the value of convergence for identifying neuropathy. They do not establish that these findings reliably distinguish painful from painless neuropathy. Indeed, the weak association between intraepidermal nerve fibre density and pain was a central argument in our position paper.&lt;/p&gt;&lt;p&gt;We acknowledge Andrea Truini's point that some laser evoked potential parameters may be less influenced by psychological modulation than response amplitude, and that methodological standardisation may improve test reliability. Nevertheless, improved reliability in d","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 10","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejp.70435","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Veratramine Alleviates Neuropathic Pain in Male Rats With Chronic Constriction Injury and Inhibits the PI3K/Akt Pathway","authors":"Yaoping Yu,&nbsp;Lijun Wang,&nbsp;Jie Cui,&nbsp;Yu Zhang,&nbsp;Fei Zhang","doi":"10.1002/ejp.70383","DOIUrl":"10.1002/ejp.70383","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuropathic pain (NP), a debilitating complication of chronic diseases such as diabetes and cancer, remains inadequately managed by current therapies; approximately 30% of patients are unresponsive to monotherapy. This study investigates the effects and potential mechanisms of veratramine, a natural compound, in a rodent model of chronic constriction injury (CCI)–induced neuropathic pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>NP was induced via CCI in rodents. Veratramine's effects were assessed through behavioural tests (mechanical withdrawal threshold [MWT] and thermal withdrawal latency [TWL]). Apoptosis and inflammation in the sciatic nerve were analysed. Western blotting and immunofluorescence evaluated phosphorylation of NF-κB, IκB, p38 MAPK, and spinal glial activation. Transcriptome profiling identified key pathways, validated using the PI3K/Akt agonist 740 Y-P.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Veratramine significantly increased MWT and TWL, alleviating mechanical and thermal hypersensitivity. It reduced neuronal apoptosis and inflammatory cytokine release at injury sites. Protein analysis showed suppressed phosphorylation of NF-κB, IκB, and p38 MAPK, alongside reduced numbers of Iba-1-positive and GFAP-positive cells in the spinal dorsal horn. Transcriptome data implicated PI3K/Akt signalling pathway inhibition, confirmed by 740 Y-P co-treatment reversing veratramine's anti-inflammatory and analgesic effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings indicate that veratramine attenuates neuropathic pain in CCI rats, and its effects may involve inhibition of the PI3K/Akt signalling pathway, leading to reduced neuroinflammation and apoptosis. This study supports a role for veratramine in the modulation of neuropathic pain and highlights the PI3K/Akt pathway as a potential target for further investigation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>The results of this study suggest that veratramine alleviates neuropathic pain in a rat model of CCI, and this effect is associated with suppression of the PI3K/Akt signalling pathway. These findings support a role for veratramine in modulating neuroinflammation and apoptosis, and may contribute to a better understanding of the molecular mechanisms involved in neuropathic pain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 9","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180197","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":"Hospital Anxiety and Depression Scale Trajectories and Risk of Complex Regional Pain Syndrome in Middle-Aged Women After Surgical Treatment of Acute Distal Radial Fracture: A Prospective Longitudinal Cohort Study","authors":"Meihui Gao,&nbsp;Jun Xiong,&nbsp;Ran Gao,&nbsp;Yun Shen,&nbsp;Shengdi Lu,&nbsp;Xiaoru Yang","doi":"10.1002/ejp.70422","DOIUrl":"10.1002/ejp.70422","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To identify Hospital Anxiety and Depression Scale–Anxiety (HADS-A) trajectories after surgical treatment of distal radius fracture (DRF) in middle-aged women, and their association with complex regional pain syndrome (CRPS).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Design&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Prospective longitudinal cohort study.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Setting&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Tertiary hospital, China.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Participants&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;One thousand eight hundred seventy-five consecutive women aged 40–65 years undergoing surgical fixation of acute unilateral DRF (January 2019–December 2022).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Main Outcome Measures&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Primary outcome was CRPS diagnosed by the Budapest Clinical Criteria at 3 months. HADS-A was measured at baseline and 1, 2, 3 and 6 months, with CRPS assessed at each follow-up. Latent class trajectory modelling (LCTM) defined trajectory classes; time in target range (TTR) was the proportion of assessments with HADS-A &lt; 8.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;During 6-month follow-up, 150 women (8.0%) developed CRPS. LCTM identified four trajectories: low-stable (&lt;i&gt;n&lt;/i&gt; = 983, 52.4%), moderate-recovering (&lt;i&gt;n&lt;/i&gt; = 448, 23.9%), high-persistent (&lt;i&gt;n&lt;/i&gt; = 265, 14.1%) and delayed-onset (&lt;i&gt;n&lt;/i&gt; = 179, 9.5%). Incidence was 19.2% (high-persistent) versus 4.9% (low-stable). After adjustment, the high-persistent trajectory was associated with CRPS (odds ratio [OR] 4.85, 95% confidence interval [CI] 1.85–12.71; &lt;i&gt;p&lt;/i&gt; = 0.001). TTR showed a graded exposure–response relationship: 0% versus 100% TTR carried higher risk (adjusted OR: 4.97, 95% CI: 2.51–9.86; &lt;i&gt;p&lt;/i&gt; &lt; 0.001; &lt;i&gt;p&lt;/i&gt; for trend &lt; 0.001). Subgroup interactions were non-significant.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Persistently elevated postoperative anxiety, rather than transient distress confined to the perioperative period, was associated with CRPS after DRF surgery, with a graded exposure–response relationship between cumulative anxiety burden (HADS-A TTR) and risk. Serial psychological monitoring beyond baseline may help identify at-risk patients.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance Statement&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study provides the first evidence that longitudinal anxiety trajectory patterns, not single-timepoint assessments, independent","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 9","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180217","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}