Frontiers in pain research (Lausanne, Switzerland)最新文献

{"title":"Open and closed loop differential target multiplexed spinal cord stimulation in patients with persistent spinal pain syndrome type II: protocol for a one year European multicenter cohort study (ENDLESS).","authors":"Lisa Goudman, Kliment Gatzinsky, Vivek Mehta, Kavita Poply, Ashish Gulve, Iris Smet, Paul Murphy, Dirk Rasche, Georgios Matis, Jan Willem Kallewaard, José Manuel Trinidad, Pasquale De Negri, Philippe Rigoard, Maarten Moens","doi":"10.3389/fpain.2026.1922595","DOIUrl":"10.3389/fpain.2026.1922595","url":null,"abstract":"<p><p>Differential target multiplexed spinal cord stimulation (DTM SCS) is a stimulation paradigm for chronic pain management that aims to modulate neuron-glial interactions. In parallel, closed-loop SCS systems using evoked compound action potential (ECAP) sensing have been introduced to adjust stimulation output in response to measured neural activation. Although clinical evidence for DTM SCS has expanded, data remain limited for patients with Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), particularly regarding ECAP-controlled closed-loop DTM SCS and its implementation in routine European practice. ENDLESS aims to investigate the feasibility, safety, and longitudinal clinical outcomes associated with open-loop and closed-loop DTM SCS in patients with PSPS-T2 through a longitudinal European multicentre cohort study. ENDLESS is a prospective multicentre cohort study including at least 200 patients, with follow-up until 12 months after implantable pulse generator activation. Outcomes will be assessed at baseline and at 1, 6 and 12 months after DTM SCS initiation. The primary effectiveness endpoint is pain intensity, measured using the Visual Analogue Scale through ecological momentary assessment. Secondary effectiveness outcomes include pain intensity with and without medication use, negative affect, disability, health-related quality of life, pain medication use, clinical holistic responder status, patient impression of change, work status, pain catastrophising, symptoms of anxiety and depression, patient unwanted stimulation awareness and patient expectations. In a subset of patients, sleep, activity patterns and RR-intervals will be assessed using actigraphy. Device-derived outcomes will include time spent in different body postures, technical implantable pulse generator details, battery consumption, stimulation parameters, programming information and ECAP-related data when closed-loop DTM SCS is used. Technical issues, adverse events, serious adverse events and the proportion of successful DTM SCS trial periods will also be documented. Longitudinal mixed models will be used to evaluate changes in effectiveness outcomes over time.</p><p><strong>Trial registration number: </strong>ClinicalTrials.gov identifier NCT07211308.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"7 ","pages":"1922595"},"PeriodicalIF":2.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882610","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":"Management of pain for people with dementia living in nursing homes: stakeholders' perspectives on a prototype of a complex intervention.","authors":"Caroline Kreppen Overen, Adelheid Hummelvoll Hillestad, Maria Larsson, Cecilia Olsson, Siren Eriksen","doi":"10.3389/fpain.2026.1868719","DOIUrl":"10.3389/fpain.2026.1868719","url":null,"abstract":"<p><strong>Background: </strong>Healthcare personnel often report uncertainty about how to identify and alleviate pain in people with dementia. Up to 80% of nursing home residents with dementia are estimated to experience chronic pain. There is a lack of structured pain management interventions that focus on integrating and building upon the individual resources of people with dementia in the nursing home context. Although a prototype of such an intervention has been developed, further knowledge is needed regarding its functioning in clinical practice, relevance, and capacity to meet clinical needs. Stakeholders possess substantial field-specific knowledge. In this study, the prototype of the intervention is presented to stakeholders to increase the likelihood of a clinically relevant intervention and successful implementation.</p><p><strong>Objectives: </strong>To describe stakeholders' perspectives of the prototype regarding intervention content and relevance, and implementation strategy.</p><p><strong>Methods: </strong>Seven dyadic interviews were conducted with practice development nurses and first-line managers in nursing homes between May to June 2025 to describe their perspectives on the prototype. The transcripts were analyzed with a deductive framework analysis.</p><p><strong>Results: </strong>The intervention was regarded as relevant and as having the potential to enhance healthcare personnel competence, structure pain management, and integrate residents' resources. However, successful implementation requires integration into existing practice models, and potential moderators were identified at both the organizational and individual levels.</p><p><strong>Conclusions: </strong>This study presents an applied approach to collaborating with stakeholders in intervention development. The participants' perspectives on activities, moderators and potential outcomes of the intervention provides essential knowledge for further refinement of the intervention and future evaluation.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"7 ","pages":"1868719"},"PeriodicalIF":2.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882629","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":"Occipital nerve stimulation for refractory facial pain following occipital pain onset: a case report supporting cervicotrigeminal convergence.","authors":"Marina Raguž, Marko Tarle, Koraljka Hat, Petar Marčinković, Sven Krušić, Tonko Marinović, Darko Chudy","doi":"10.3389/fpain.2026.1917660","DOIUrl":"10.3389/fpain.2026.1917660","url":null,"abstract":"<p><strong>Introduction: </strong>Cervicotrigeminal convergence within the trigeminocervical complex (TCC) provides a neuroanatomical basis for referral of nociceptive input from upper cervical structures to trigeminal territories. However, clinical evidence linking occipital pain onset, trigeminal symptom propagation, and successful treatment with occipital nerve stimulation (ONS) remains limited.</p><p><strong>Case presentation: </strong>A 35-year-old woman developed persistent right-sided occipital, retroauricular, and upper cervical pain approximately eight years before presentation, which progressively spread into trigeminal territories. Multiple pharmacological therapies, greater occipital nerve neurolysis, microvascular decompression, and treatments targeting temporomandibular dysfunction failed to provide sustained relief. Following multidisciplinary evaluation, diagnostic greater occipital nerve (GON) blockade resulted in complete temporary resolution of pain. The patient subsequently underwent bilateral ONS, resulting in marked pain reduction (VAS 8-10/10 to 2/10), contraction of the pain distribution, discontinuation of opioid-containing analgesics, and sustained clinical improvement during follow-up.</p><p><strong>Conclusion: </strong>This case supports cervicotrigeminal convergence as a plausible mechanism underlying refractory facial pain following occipital pain onset. Complete temporary pain relief after diagnostic GON blockade and sustained improvement following ONS suggest that occipital neuromodulation may represent a therapeutic option in carefully selected patients.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"7 ","pages":"1917660"},"PeriodicalIF":2.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876710","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":"Mechanisms and clinical application of photobiomodulation in pain therapy: a mini review.","authors":"Yuxuan Ren, Weiwei Li, He Miao, Yushan Chen, Xiaowei Chen","doi":"10.3389/fpain.2026.1920821","DOIUrl":"10.3389/fpain.2026.1920821","url":null,"abstract":"<p><p>Chronic pain remains a major clinical challenge, creating a need for safe, non-pharmacological interventions. This narrative mini-review examines two light-based approaches that differ in their sites of action and treatment parameters: visual-light exposure and local red or near-infrared light-emitting diode photobiomodulation. Visual-light exposure acts through retinal and central neural circuits, including pathways involving the ventrolateral geniculate nucleus, dorsal raphe nucleus, periaqueductal gray, medial secondary visual cortex, and anterior cingulate cortex. Its effects are wavelength- and context-dependent. Green light has generally produced antinociceptive effects in preclinical studies and preliminary clinical benefits in migraine, whereas visual exposure to red light has predominantly been associated with increased pain. White light can either facilitate or suppress pain depending on irradiance, exposure duration, circadian timing, and clinical context. By contrast, locally applied red or near-infrared LEDs have reduced pain in several preclinical models and limited clinical studies through peripheral opioid signaling, modulation of nitric oxide and nociceptor sensitization, and anti-inflammatory and antioxidant effects. The opposing effects of visual and local red light indicate that wavelength alone does not determine the pain response; exposure route, target tissue, dose, timing, and baseline pain state are also critical. Although visual-light interventions and local LED PBM appear promising as adjuncts to conventional treatment, the evidence remains limited by heterogeneous protocols, small clinical samples, and incomplete dosimetric reporting. Future studies should use standardized parameters, rigorous controls, and condition-specific protocols to establish efficacy and identify patients most likely to benefit.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"7 ","pages":"1920821"},"PeriodicalIF":2.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876759","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":"Bilateral nervus intermedius neuralgia with neurovascular contact: a case report highlighting hypertension and eczema as potential precipitating factors.","authors":"Shusheng Jiao, Yi Zhou, Yanxia Zhu, Zhekai Zhang, Haoyuan Ma","doi":"10.3389/fpain.2026.1862625","DOIUrl":"10.3389/fpain.2026.1862625","url":null,"abstract":"<p><strong>Background: </strong>Nervus intermedius neuralgia (NIN) is a rare craniofacial pain syndrome. Bilateral involvement is extremely uncommon, and the pathophysiology and precipitating factors of NIN remain poorly understood.</p><p><strong>Case presentation: </strong>A 57-year-old female presented with a 3-month history of bilateral paroxysmal stabbing deep ear pain triggered by cold wind and auricular pressure, superimposed on a persistent dull ache. She had a 5-year history of hypertension, with poor blood pressure control (140-160/90-105 mmHg) for four months preceding symptom onset. Otoscopic examination revealed bilateral external auditory canal eczema. Dedicated cranial MRI demonstrated bilateral anterior inferior cerebellar artery (AICA) loops in contact with the facial-vestibulocochlear nerve complexes, with no vascular contact at the trigeminal or glossopharyngeal nerves. A clinical diagnosis of bilateral NIN was established according to ICHD-3 criteria. The patient responded favorably to pregabalin combined with strict blood pressure control. At three-month follow-up, her stabbing pain had essentially resolved (VAS: 0-1/10).</p><p><strong>Conclusion: </strong>This first case of bilateral NIN with radiologically confirmed bilateral neurovascular contact supports neurovascular conflict as a pathophysiological mechanism even in bilateral presentations. Uncontrolled hypertension and local inflammation may serve as potential precipitating factors. A conservative approach combining pharmacotherapy with cardiovascular risk factor management may achieve favorable outcomes, potentially avoiding surgery in selected patients.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"7 ","pages":"1862625"},"PeriodicalIF":2.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876654","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":"Electromagnetic neuromodulation for chronic pain: historical context, contemporary modalities, and evidence gaps.","authors":"Laura Dipietro, Ciro Ramos-Estebanez, Paola Gonzalez-Mego, Anna Carolyna Gianlorenco, Arisara Wongtanawat, Christopher Robinson, Salim M Hayek, Felipe Fregni, Timothy Wagner","doi":"10.3389/fpain.2026.1901466","DOIUrl":"10.3389/fpain.2026.1901466","url":null,"abstract":"<p><p>Electromagnetic neuromodulation is increasingly used as an adjunct or alternative to pharmacologic therapy for pain, with several approaches cleared for select indications and many others under active investigation. We review implanted neuromodulation approaches (intracranial and spinal), vagal neuromodulation, noninvasive central/cranial neuromodulation, peripheral neuromodulation, and hybrid/multimodal approaches, with a primary focus on chronic pain management and brief coverage of selected acute-use indications (e.g., primary headache disorders) where relevant. Beyond summarizing individual modalities, we highlight the recurring patterns that have shaped the evolution of pain neuromodulation. For each modality, we summarize putative mechanism of action, typical stimulation paradigms, and key strengths and limitations of the clinical evidence, emphasizing sources of heterogeneity that complicate cross-study comparison and translation. We conclude by outlining priorities for the field, including more rigorous trial design, standardized reporting of stimulation parameters and outcomes, and clearer indication-specific evidence to support clinical translation.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"7 ","pages":"1901466"},"PeriodicalIF":2.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876641","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":"Editorial: A lifespan approach towards paediatric pain management: from neonates to young adults.","authors":"L Caes, J McParland, H Durand","doi":"10.3389/fpain.2026.1933896","DOIUrl":"10.3389/fpain.2026.1933896","url":null,"abstract":"","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"7 ","pages":"1933896"},"PeriodicalIF":2.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876629","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":"Impact of genetic polymorphisms on the response to transdermal fentanyl in cancer patients-a single-center, prospective, biological study.","authors":"Lucia Angelini, Irene Azzali, Andrea Carlini, Vincenza Andrisano, Serena Montanari, Monia Dall'agata, Giorgia Simonetti, Maria Teresa Bochicchio, Matteo Paganelli, Vanessa Valenti, Paola Cravero, Margherita Currà, Linda Petrini, Costanza Maria Donati, Alessio G Morganti, Andrea Ardizzoni, Oscar Edoardo Corli, Marco Cesare Maltoni, Romina Rossi, Marianna Ricci","doi":"10.3389/fpain.2026.1834786","DOIUrl":"10.3389/fpain.2026.1834786","url":null,"abstract":"<p><strong>Background/objectives: </strong>Transdermal fentanyl (TDF) is widely used for moderate-to-severe cancer pain, yet substantial variability in fentanyl exposure, analgesic response, and tolerability remains incompletely explained by clinical factors. We evaluated whether pharmacogenetic variability is associated with pharmacokinetic parameters and clinical outcomes in cancer patients receiving TDF.</p><p><strong>Methods: </strong>In this prospective, single-center study, adults with solid or hematological malignancies and chronic cancer pain treated with stable-dose 72 h TDF were enrolled. Blood samples were collected for pharmacokinetic and pharmacogenetic analyses. Serum fentanyl concentrations were quantified using validated gas chromatography-mass spectrometry, and AUC, C_max, and t_max were calculated using non-compartmental analysis. Genotyping was performed using a predefined pharmacogenetic panel. Analgesic response was defined as a ≥2-point reduction in Numeric Rating Scale score or score = 0 at 72 h. Statistical analyses included correction for multiple testing.</p><p><strong>Results: </strong>49 patients were included (median age 65 years; 98% stage IV disease); 38 (77.5%) were responders. No significant differences in AUC, C_max, or t_max were observed between responders and non-responders. TPMT and UGT2B7 variants showed unadjusted associations with clinical response and pharmacokinetic parameters, respectively; however, none remained statistically significant after correction for multiple testing. No significant associations were observed for CYP3A4/5 or ABCB1 variants, nor between genetic variants and adverse events. Pain reduction correlated with improved functional outcomes.</p><p><strong>Conclusions: </strong>In this exploratory cohort, pharmacogenetic variability was not robustly associated with TDF pharmacokinetics, analgesic response, or tolerability after correction for multiple testing. These findings do not support the current clinical implementation of pharmacogenetic-guided TDF therapy, but provide hypothesis-generating signals for future studies.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"7 ","pages":"1834786"},"PeriodicalIF":2.5,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868108","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":"Orthobiologics are not all the same: a mechanism-based scoping review of PRP, cytokine-rich serum, and extracellular vesicle-based strategies in musculoskeletal conditions.","authors":"Luigi Di Lorenzo, Alfonso M Forte, Bruno De Meo, Francesco Forte, Carmine D'Avanzo, Hassan Zmerly","doi":"10.3389/fpain.2026.1772644","DOIUrl":"10.3389/fpain.2026.1772644","url":null,"abstract":"<p><p>Autologous blood-derived orthobiologics, including platelet-rich plasma and cytokine-rich serum, are widely used in musculoskeletal medicine. Extracellular vesicle-based approaches are increasingly investigated as related biologically active strategies, although they may derive from multiple autologous or allogeneic cellular and tissue sources. However, these biologics differ significantly in composition and mechanism of action, often leading to confusion in terminology and inconsistent clinical application. This scoping review critically maps current evidence (2020-2025) from randomized trials, systematic reviews, and meta-analyses to clarify the biological heterogeneity among these products. Platelet-based PRP acts primarily via growth factor release, supporting anabolic and reparative processes. Leukocyte- and monocyte-containing PRP formulations, conversely, engage immune modulation and inflammatory signaling pathways. Acellular cytokine-rich sera (e.g., autologous conditioned serum) offer immunomodulatory effects through soluble mediators like IL-1Ra. EVs and exosomes represent a promising but still experimental approach, functioning as paracrine modulators with unclear clinical efficacy. While some formulations yield similar clinical outcomes, these cannot be interpreted as biologically equivalent. The only triple-blind randomized trial on exosomes in knee osteoarthritis confirmed safety but no superiority over placebo. A mechanism-informed, indication-driven selection is essential to optimize treatment efficacy, avoid inappropriate expectations, and advance the field responsibly. This review proposes a biologically grounded classification of orthobiologics and highlights the need for standardized reporting, accurate product characterization, and rigorous clinical validation. Clinicians and researchers are urged to abandon the \"one-size-fits-all\" approach and embrace biological specificity when selecting orthobiologic therapies for musculoskeletal conditions.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"7 ","pages":"1772644"},"PeriodicalIF":2.5,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868090","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 and sensory abnormalities in prodromal and early Parkinson's disease: mechanisms, assessment, and clinical implications.","authors":"Maria Skallerup Andersen, Lorenz Martin Oppel, Boris Modrau, Kimmo Jensen, Parisa Gazerani","doi":"10.3389/fpain.2026.1888196","DOIUrl":"10.3389/fpain.2026.1888196","url":null,"abstract":"<p><p>Parkinson's disease (PD) is traditionally characterized by motor symptoms; however, non-motor symptoms, particularly pain and sensory disturbances, are increasingly recognized as potential early manifestations that precede motor onset. Pain has been reported in up to 59% of patients before the onset of motor symptoms and in up to 72% in the early stages of PD, yet its underlying mechanisms and clinical implications remain insufficiently understood. Emerging evidence suggests that dopaminergic dysfunction may alter nociceptive processing across both peripheral and central pathways, involving changes within spinal, brainstem, and cortical pain networks. Despite this, the heterogeneity of pain phenotypes and the lack of standardized assessment approaches continue to limit the diagnostic and clinical utility of pain as an early disease indicator. Importantly, early pain symptoms may lead to misinterpretation and unnecessary investigations, potentially delaying PD diagnosis. This narrative review critically examines four key aspects of pain in prodromal to early-stage PD: (1) pain as an early clinical feature, (2) underlying nociceptive and neurodegenerative mechanisms, (3) alterations in small-fiber function assessed by quantitative sensory testing, and (4) large-fiber involvement evaluated through nerve conduction studies. By integrating current evidence, this review highlights the role of pain as a potential early indicator of PD, synthesizes current knowledge on sensory dysfunction across the prodromal to early disease spectrum, and identifies key gaps to support diagnosis, improved patient stratification, and mechanism-based management strategies.</p>","PeriodicalId":73097,"journal":{"name":"Frontiers in pain research (Lausanne, Switzerland)","volume":"7 ","pages":"1888196"},"PeriodicalIF":2.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868153","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}