Neurobiology of Pain最新文献

{"title":"Exercise-induced hypoalgesia in healthy males is best explained by mechanisms selectively affecting deep-tissue pain sensitivity within exercising body parts","authors":"Vladimir Aron,&nbsp;Thomas Graven-Nielsen,&nbsp;Louise Deldicque,&nbsp;André Mouraux","doi":"10.1016/j.ynpai.2026.100221","DOIUrl":"10.1016/j.ynpai.2026.100221","url":null,"abstract":"<div><h3>Background</h3><div>The mechanisms driving the transient reduction in pain sensitivity following a single bout of physical exercise—a phenomenon known as exercise-induced hypoalgesia (EIH)—remain unclear despite proposed contributions from central and peripheral processes. So far it is unknown whether EIH selectively modulates the perception of specific types of nociceptive stimuli and whether this modulation is confined to exercising limbs or generalized to the entire body.</div></div><div><h3>Methods</h3><div>In 38 healthy males (18–30 years) the effects of a single session of moderate/high-intensity cycling exercise (25 min at 75% of the heart rate reserve) were assessed against a control condition (25 min of light cycling exercise) on the sensitivity to stimuli preferentially activating skin mechano- and heat-sensitive nociceptors versus deep-tissue nociceptors, applied to the exercising lower limbs versus the non-exercising upper limbs. Pressure pain thresholds (PPT), heat pain thresholds (HPT), cold detection thresholds (CDT), and mechanical pinprick ratings (PP), as well as auditory detection thresholds (ADT) serving as control, were recorded before and immediately after the exercise and control conditions.</div></div><div><h3>Results</h3><div>Linear mixed models revealed that exercise increased the PPT selectively at the exercising limb. No significant effects of exercise were found for other types of stimuli, except for a reduction of CDT at the exercising limb, which was not significant when controlling for skin temperature.</div></div><div><h3>Conclusions</h3><div>These findings suggest that processes preferentially modulating deep-tissue nociceptor sensitivity within exercising muscles contribute to EIH in young healthy males.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100221"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148377907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain in the claustrum","authors":"Christian Faig,&nbsp;Chun Yin Liu,&nbsp;Jesse Jackson,&nbsp;Brian N. Mathur,&nbsp;David A. Seminowicz,&nbsp;Anna M.W. Taylor","doi":"10.1016/j.ynpai.2026.100228","DOIUrl":"10.1016/j.ynpai.2026.100228","url":null,"abstract":"<div><div>Pain arises from coordinated activity across distributed brain networks. The claustrum, a thin subcortical nucleus with extensive bidirectional connectivity with the neocortex, has recently emerged as a potential hub in this network. Although historically difficult to isolate due to its thin anatomical structure and proximity to other pain-associated regions, recent advances in neuroimaging and circuit-specific manipulations have revealed new insights into its role in pain. This review synthesizes the evidence from human and animal studies and evaluates the evidential strength of current approaches, ranging from incidental reporting in whole-brain neuroimaging studies to claustrum-targeted imaging, electrophysiology and projection-specific manipulations. The literature suggests that the claustrum contributes to pain not as a primary sensory relay, but as a modulatory and integrative structure influencing various facets of cognition. We have organized these findings into three theory-guided frameworks: (1) sensory filtering of salient stimuli, (2) cognitive network engagement, and (3) offline consolidation of pain-related memory during rest and sleep. In chronic pain, claustrocortical function is altered in ways that map onto each of these frameworks, with rodent models pointing to depressed claustrocingulate output and loss of inhibitory control, and human imaging linking claustrum signals to catastrophizing, expectancy, and altered network recruitment. Taken together, the evidence highlights the claustrum as a promising but incompletely understood node in pain circuitry and underscores the need for more anatomically precise and mechanistically decisive studies to define its contribution to normal and pathological pain states.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100228"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148656672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation DNA methylation sequencing: loci and regions differentially methylated in adolescents with chronic postsurgical pain","authors":"Siva Athitya Lakshamana Vijayarajan,&nbsp;Kristen N. Krolick,&nbsp;Xue Zhang,&nbsp;Lisa J. Martin,&nbsp;Susan Glynn,&nbsp;Kristi Cole,&nbsp;Victor Garcia,&nbsp;Hong Ji,&nbsp;R.J. Ramamurthi,&nbsp;L.M. Einhorn,&nbsp;C.L. Monitto,&nbsp;A. Ganesh,&nbsp;Vidya Chidambaran","doi":"10.1016/j.ynpai.2026.100229","DOIUrl":"10.1016/j.ynpai.2026.100229","url":null,"abstract":"<div><div>DNA methylation (DNAm) may link environmental exposures to pain susceptibility. We examined preoperative DNAm patterns (using next-generation enzymatic-methylation sequencing) associated with chronic postsurgical pain (CPSP), a major biopsychosocial problem in adolescents undergoing musculoskeletal surgeries, recruited across six sites (<em>n</em> = 166; 15.5 (IQR 14.3–16.8) years; 51% male). Pain and functional measures were followed longitudinally. CPSP was defined as pain&gt;3/10 beyond two months post-surgery. We identified 289 differentially methylated loci (DML; HB <em>p</em> &lt; 0.1) that satisfied robustness criteria after bootstrapping, and 20 regions (DMR) (FDR <em>p</em> &lt; 0.05) associated with CPSP. Using CPSP-specific background, DMLs, annotated to 57 genes, were enriched for biological processes (Cellular response to cAMP (<em>p</em> = 0.001), neuronal action potential (<em>p</em> = 0.01), sodium ion transmembrane transport (<em>p</em> = 0.03), potassium ion transmembrane transport (<em>P</em> = 0.035) and regulation of postsynaptic membrane potential (<em>P</em> = 0.041)), molecular functions (Intracellular camp-activated cation channel activity (<em>p</em> = 0.001), cAMP binding (<em>p</em> = 0.003), voltage-gated sodium channel activity (<em>p</em> = 0.01), and voltage-gated potassium channel activity (<em>p</em> = 0.02)), and cellular components (HCN channel complex (<em>p</em> = 0.002), presynaptic active zone membrane (<em>p</em> = 0.006), and postsynaptic membrane (<em>p</em> = 0.049)). DMRs did not enrich gene pathways but showed transcription factor motif enrichment for stress response (TGF-β/SMAD), neuronal differentiation/plasticity (NR4A/TEAD), inflammation/immunity (STATs), and circadian signaling (RORA/RORB/NPAS2). Study findings suggest potential DNAm signatures associated with CPSP and generate hypotheses regarding their possible role in CPSP development.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100229"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148735216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant anterior insula-sensorimotor interaction modulates pain empathy in women with primary dysmenorrhea","authors":"Meiling Shang,&nbsp;Tongtong Fan,&nbsp;Yanran Chen,&nbsp;Huiping Liu,&nbsp;Jing Yang,&nbsp;Ke Wang,&nbsp;Hui Li,&nbsp;Wanghuan Dun","doi":"10.1016/j.ynpai.2026.100225","DOIUrl":"10.1016/j.ynpai.2026.100225","url":null,"abstract":"<div><div><em>Background:</em> Pain empathy engages multiple neural networks. Neuroimaging research has identified anterior insula (aINS) and the sensorimotor network in processing pain empathy among women with primary dysmenorrhea (PDM). However, it remains unclear how the interaction between the two networks modulates pain empathy during menstrual pain.</div><div><em>Methods:</em> This case–control study included 56 women with PDM and 55 healthy controls (HCs). Participants were instructed to take functional MRI (fMRI) scans during the menstrual phase and view images depicting painful and non-painful situations to elicit empathy, as well as the short form of McGill Pain Questionnaire to elicit pain intensity. Functional connectivity (FC) analyses of the aINS-related and sensorimotor networks, and their interactions, were conducted to investigate their relationship with pain and pain empathy. Mediation analysis was performed to investigate the role of FC mediating menstrual pain and empathy.</div><div><em>Results:</em> PDM patients exhibited higher scores of pain empathy, which was significantly correlated with pain intensity. With comparable bilateral aINS-precentral/postcentral FC, left aINS–postcentral connectivity showed positive correlations with both pain intensity and empathy in PDM patients, whereas.</div><div>the positive interaction between the left aINS- and precentral-centered networks was inversely associated with pain empathy in HCs. Furthermore, correlation and mediation analyses revealed that left aINS-right postcentral FC mediated the relationship between menstrual pain and pain empathy in PDM women.</div><div><em>Conclusion:</em> aINS–sensorimotor network interactions play a critical role in pain empathy, which may nonetheless engage in divergent regulatory processes under menstrual pain, shaping psychological adaptation and empathic responses.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100225"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148587563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cooling a burning mouth: is TRPM8 the therapeutically relevant target of clonazepam in burning mouth disorder?","authors":"Logan Elkin,&nbsp;Jonathan S. Marchant","doi":"10.1016/j.ynpai.2026.100232","DOIUrl":"10.1016/j.ynpai.2026.100232","url":null,"abstract":"<div><div>Burning mouth disorder (BMD) is an extremely painful oral condition that occurs at the highest prevalence in post-menopausal women. Treatment options remain limited and remission rates poor, highlighting a need for identification of relevant molecular targets that can be prosecuted for effective therapeutics. One treatment that realizes benefit in patients with burning mouth disorder is clonazepam, a benzodiazepine known to work by augmenting currents through gamma aminobutyric acid A (GABA_A) ion channels to inhibit neuronal firing. Here, we highlight an ancillary target for clonazepam as the transient receptor potential melastatin 8 (TRPM8) ion channel. In this commentary, evidence supporting the idea that TRPM8 acts as the therapeutically relevant local mediator of clonazepam action in BMD is summarized, with the goal of spurring new treatments for this debilitating and painful condition.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100232"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149050970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional–secretory uncoupling in RDEB skin creates a non-permissive microenvironment for sensory nerve regeneration","authors":"Paula Diaz,&nbsp;Carolina Flores-Muñoz,&nbsp;Margarita Calvo","doi":"10.1016/j.ynpai.2026.100223","DOIUrl":"10.1016/j.ynpai.2026.100223","url":null,"abstract":"<div><div>Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin fragility disorder caused by mutations in <em>COL7A1</em> gene, leading to chronic injury, inflammation, and debilitating sensory symptoms, including pain and itch. While structural defects in the dermo-epidermal junction are well characterized, the mechanisms underlying impaired sensory reinnervation and neuropathic manifestations remain poorly understood. Here, we investigated whether defective reinnervation in RDEB is driven by intrinsic neuronal deficits or by alterations in the cutaneous microenvironment. Using a prospective cohort of RDEB patients with small fiber neuropathy (SFN), combined with high-resolution digital PCR and multiplex cytokine profiling, we analyzed the transcriptional and secretory responses of wounded skin and primary keratinocytes. RDEB tissue exhibited a markedly blunted transcriptional response to injury, with failure to induce key inflammatory, proteolytic, and axonal guidance genes, despite a sustained pro-inflammatory secretome characterized by elevated IL-6, TNF-α, IL-1β, CCL2, and MMP9. Functionally, RDEB blister fluid induced growth cone collapse and impaired neurite outgrowth in sensory neurons. These findings reveal a dissociation between transcriptional activation and extracellular signalling, resulting in a non-permissive niche for nerve regeneration. We propose that this altered microenvironment simultaneously impairs reinnervation and promotes maladaptive nociceptive signalling, providing a mechanistic link between chronic denervation and neuropathic pain in RDEB.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100223"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148431492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory T cells promote sensory neuron growth and protect against neurotoxicity","authors":"Jessica P. Hayes,&nbsp;Sandra Fok,&nbsp;Renee Whan,&nbsp;Gary D. Housley,&nbsp;Gila Moalem-Taylor","doi":"10.1016/j.ynpai.2026.100224","DOIUrl":"10.1016/j.ynpai.2026.100224","url":null,"abstract":"<div><div>Regulatory T cells (Tregs) maintain immune homeostasis and suppress inflammation, and emerging evidence indicates they also modulate neuronal function and regeneration. Dorsal root ganglion (DRG) sensory neurons transmit pain signals and are damaged by chemotherapeutic agents such as paclitaxel (PTX), leading to neuropathic pain. Although Tregs show therapeutic promise in neuropathic pain, the mechanisms of Treg–neuron interactions remain poorly defined. Using in vitro co-culture, we examined interactions between primary DRG neurons and Tregs and their effect on PTX-induced neurotoxicity. Live-cell imaging showed that activated Tregs enhanced neurite length and branching and preferentially localised to neuron/neurite-rich regions. Additionally, activated Tregs rescued PTX-induced inhibition of neurite outgrowth. Pharmacological blockade identified Treg-derived amphiregulin (AREG) as essential for neurite outgrowth, while both AREG and neuropeptide Y were required for Treg-mediated protection against PTX-induced neurotoxicity. These findings identify Tregs as direct promoters of sensory neuron growth and protection from PTX-induced neurotoxicity through specific molecular mediators, supporting their potential therapeutic relevance in peripheral neuropathic pain.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100224"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148587564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific differences in nociceptive behaviour and the amygdala endocannabinoid system in the rat monoiodoacetate-induced knee osteoarthritis model","authors":"Mehnaz I. Ferdousi,&nbsp;Rosmara Infantino,&nbsp;Maria C. Redmond,&nbsp;Santhosh D. Krishnan,&nbsp;Canny K. Adjei,&nbsp;Barry McDermott,&nbsp;Alison Liddy,&nbsp;Leo Quinlan,&nbsp;Martin O'Halloran,&nbsp;David P. Finn","doi":"10.1016/j.ynpai.2026.100227","DOIUrl":"10.1016/j.ynpai.2026.100227","url":null,"abstract":"<div><h3>Introduction</h3><div>Osteoarthritis (OA) is a chronic, progressive joint disorder with higher prevalence and pain severity in women than men. The endocannabinoid system (ECS) modulates pain and shows sexual dimorphism, yet sex-specific alterations in central ECS signalling in OA pain remain under-investigated.</div></div><div><h3>Objectives</h3><div>We investigated sex-dependent differences in pain-related behaviours and central ECS signalling in the rat monoiodoacetate (MIA) model of knee OA pain.</div></div><div><h3>Methods</h3><div>Adult male and female Sprague-Dawley rats (8-9 weeks old) received an intra-articular injection of either MIA (2 mg/50 μL) or saline (Sham control) in the left knee. Pain-related behaviours were assessed over 63 days post-injection. The influence of oestrous cycle stage on pain-related behaviours was examined in 100 additional MIA-injected female rats. Endocannabinoids [anandamide (AEA), 2-arachidonoylglycerol (2-AG)] and <em>N</em>-acylethanolamines [palmitoylethanolamide (PEA), oleoylethanolamide (OEA)] were quantified in brain and spinal cord regions (LC-MS/MS), and ECS-related gene expression (<em>Faah</em>, <em>Mgll</em>, <em>Cnr1</em>, <em>Cnr2</em>) was assessed (RT-qPCR).</div></div><div><h3>Results</h3><div>MIA females exhibited greater weight-bearing deficits and hind paw mechanical hypersensitivity than males throughout the study period. Oestrous cycle stage did not influence MIA-induced pain-related behaviours. MIA males showed lateralised ECS signalling in the amygdala, with elevated endocannabinoid and <em>N</em>-acylethanolamine levels in the ipsilateral/left amygdala, a pattern absent in females. A bilateral reduction of <em>Mgll</em> expression in the amygdala was observed in MIA female rats compared to Sham controls.</div></div><div><h3>Conclusions</h3><div>In the MIA model, female rats demonstrate greater nociceptive behaviour and a different amygdala ECS profile, compared with males, paving the way for further investigation of ECS-mediated mechanisms underlying sex differences in OA pain.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100227"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148656675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma levels and peripheral DNA methylation of IGF-1 and IGF-2 across knee osteoarthritis pain phenotypes in middle-aged and older adults","authors":"Muhammad Abbas,&nbsp;Javier A. Tamargo,&nbsp;Yutao Zhang,&nbsp;Carlos J. Cruz,&nbsp;John Gilliam,&nbsp;Stephanie Wohlgemuth,&nbsp;Kevin Wu,&nbsp;Roland Staud,&nbsp;Li Chen,&nbsp;Burel R. Goodin,&nbsp;Roger B. Fillingim,&nbsp;Christiaan Leeuwenburgh,&nbsp;Yenisel Cruz-Almeida","doi":"10.1016/j.ynpai.2026.100233","DOIUrl":"10.1016/j.ynpai.2026.100233","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a leading cause of pain and disability, yet the biological mechanisms linking structural disease and pain remain incompletely understood. Insulin-like growth factors (IGFs) are involved in cartilage homeostasis, inflammation, and pain signaling and may serve as biomarkers or therapeutic targets in OA. This exploratory cross-sectional study examined associations between circulating levels and peripheral blood DNA methylation of <em>IGF1 and IGF2</em> with chronic knee OA pain phenotypes in 158 adults aged 45–85 years with and without symptomatic knee OA. Participants were classified into five radiographic OA (ROA)-pain phenotypes based on pain impact and Kellgren-Lawrence grade: no pain/no ROA, pain/no ROA, pain/late ROA, high-impact pain/early ROA, and low-impact pain/early ROA. In adjusted analyses, ROA-pain phenotypes were associated with circulating IGF-1 and IGF-2 levels in a sex-dependent manner. Females with low-impact pain and early ROA had higher IGF-1 levels than males in the same phenotype. For IGF-2, males with no ROA, with and without pain, had higher levels than males with high-impact pain and early ROA, and males with no pain/no ROA also had higher IGF-2 levels than females. Mean DNA methylation levels of <em>IGF1</em> and <em>IGF2</em> showed limited associations after covariate adjustment, and no probe-level findings survived multiple-testing correction. These findings identify sex-dependent associations between circulating IGF-1 and IGF-2 and knee OA pain phenotypes, most notably lower IGF-2 in males with high-impact pain and early radiographic disease. The largely null peripheral methylation results suggest that tissue-level epigenetic regulation of IGF pathways, beyond what the buffy coat captures, warrants further investigation in larger cohorts.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100233"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypertension and pain: A state-based framework for cardiovascular–nociceptive coupling","authors":"Basak Donertas-Ayaz,&nbsp;Carlos J. Cruz,&nbsp;John K. Neubert,&nbsp;Robert M. Caudle","doi":"10.1016/j.ynpai.2026.100236","DOIUrl":"10.1016/j.ynpai.2026.100236","url":null,"abstract":"<div><div>Experimental and epidemiological studies suggest that blood pressure (BP)-pain associations vary across normotension, hypertension, and chronic pain, but the mechanisms underlying these differences remain unclear. In pain-free individuals, higher resting BP is often associated with lower experimental pain sensitivity. Similar hypoalgesia is reported in some normotensive individuals with familial hypertension risk and in established hypertension, suggesting that reduced pain sensitivity is unlikely to be attributable to elevated BP alone. Acute baroreceptor activation can inhibit nociceptive reflexes and pain ratings, and current evidence points to contributions from baroreflex, autonomic, opioid, sensory, vascular, and renin-angiotensin pathways in BP-related hypoalgesia across groups. In chronic pain, the inverse BP-pain association is often weaker, absent, or reversed for selected pain facilitation measures. Prospective epidemiological studies suggest that chronic pain may be associated with increased later hypertension risk, although these observational findings do not establish causality. This review organizes the literature into four states: familial hypertension risk without sustained hypertension, inverse BP-pain associations in normotensive individuals, hypoalgesia in established hypertension, and attenuated or reversed BP-pain associations in chronic pain. Longitudinal studies are needed to determine whether these patterns reflect distinct phenotypes, transitional processes, overlapping mechanisms, or study-context differences.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100236"},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149211193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}