Journal of Pain最新文献

{"title":"Next steps in understanding and addressing chronic pain risk among transgender people: Comment on Stocking et al. (2025).","authors":"Benjamin P Van Dyke","doi":"10.1016/j.jpain.2025.105405","DOIUrl":"https://doi.org/10.1016/j.jpain.2025.105405","url":null,"abstract":"","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":" ","pages":"105405"},"PeriodicalIF":4.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049745","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":"Trajectories of change in pediatric functional abdominal pain disorders during Internet cognitive behavior therapy: A single case experimental study","authors":"Eva Skovslund Nielsen MD, PhD-student ,&nbsp;Karen Kallesøe MD, PhD ,&nbsp;Maria Lalouni Msc, PhD ,&nbsp;Anders Helles Carlsen Msc ,&nbsp;Lisbeth Frostholm Msc, PhD ,&nbsp;Marianne Bonnert Msc, PhD ,&nbsp;Charlotte Ulrikka Rask MD, PhD","doi":"10.1016/j.jpain.2025.105407","DOIUrl":"10.1016/j.jpain.2025.105407","url":null,"abstract":"<div><div>Functional abdominal pain disorders (FAPDs) are prevalent in youth and affect daily life. Therapist-supported Internet-delivered cognitive-behavioral-therapy (ICBT) is promising, though the detailed trajectories of therapeutic effects unknown.</div><div>This study aimed to analyze trajectories of effect and timing of changes in abdominal symptoms (primary outcome) and psychological factors (catastrophizing, avoidance and control behavior, pain acceptance (secondary outcomes)) in children and adolescents during 10 weeks of exposure-based ICBT for FAPDs in a randomized multiple-baseline single-case experimental design study in six children and six adolescents with FAPDs, referred from pediatric departments. Outcomes were assessed daily during baseline (A), treatment (B1: Main treatment components, B2: Training repeated exposures), and three-month follow-up (C). Effects were evaluated with visual analyses, Tau-U effect sizes for each individual, and multilevel modeling for group-level effects.</div><div>All participants completed all treatment modules. Individually, treatment effectively reduced abdominal symptoms in half of the participants at three-month follow-up, following diverse trajectories with varying sequences of secondary outcome changes. At group-level, children demonstrated significant effects on estimated means of all outcomes at follow-up (P&lt;0.05), while adolescents did on all outcomes (P&lt;0.05) except one pain acceptance item (pain control). The group trajectories differed: children showed significant daily changes in abdominal symptoms during treatment B2, while adolescents exhibited significant slopes in most outcomes except one pain acceptance item (pain control) as early as during treatment B1.</div><div>The findings support the effect of ICBT for FAPDs in youth, although with varying effect trajectories and differences in the timing of outcome changes across individuals and age-groups.</div></div><div><h3>Perspectives</h3><div>This study provides evidence for the effect of ICBT in managing FAPDs in children and adolescents while uncovering individual and age-related differences in trajectories of changes in abdominal symptoms and psychological factors. Clinicians and researchers can use these findings to refine treatment protocols and explore mechanisms underlying these variations.</div></div><div><h3>Clinical trial preregistration</h3><div>NCT05237882</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"31 ","pages":"Article 105407"},"PeriodicalIF":4.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900111","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":"How the clinical encounter shapes diagnostic uncertainty in pediatric chronic pain","authors":"Alexandra Neville PhD ,&nbsp;Ignasi Clemente PhD ,&nbsp;Marcia L. Meldrum PhD ,&nbsp;Lonnie Zeltzer MD ,&nbsp;Abbie Jordan PhD ,&nbsp;Tim F. Oberlander MD, FRCPC ,&nbsp;Katelyn Watson ,&nbsp;Jennifer Daly-Cyr ,&nbsp;Melanie Noel PhD","doi":"10.1016/j.jpain.2025.105406","DOIUrl":"10.1016/j.jpain.2025.105406","url":null,"abstract":"<div><div>Approximately one third of youth with chronic primary pain receiving care in a tertiary care pediatric pain setting, and their parents, report diagnostic uncertainty, which is associated with poorer child pain outcomes and is intricately tied to clinical communication along the pain care journey. This study utilized archived data (collected 2003–2006) to explore components of the clinical encounter that influence diagnostic uncertainty among youth with chronic pain and their parents. Twenty-three youth with chronic primary pain and at least one of their parents who presented for an initial visit at a tertiary pediatric pain clinic participated. Initial clinic intake visits were audio and video recorded, and youth and parents participated in semi-structured interviews prior to, and several months following, their intake appointment. Transcripts of clinical encounters and pre- and post-interviews were analyzed using interpretative phenomenological analysis. Analyses generated four themes: 1) Diagnostic uncertainty is a social phenomenon critically shaped in clinical encounters; 2) (In)validation of pain, the journey, and diagnostic uncertainty; 3) The (missing) link between origin story &amp; pain explanation; and 4) The fragility of certainty. These themes illustrate that youth’s and parents’ experiences of diagnostic uncertainty are complex, dynamic, and shaped within clinical encounters. The actions taken and explanations provided by clinicians in the clinical encounter can heighten or lower diagnostic uncertainty. Clinician communication, including (in)validation, messages of (un)certainty, elicitation of youth’s and parents’ pain origin stories and their connection to a pain explanation, influence diagnostic uncertainty and could be targets for assessment, training, and intervention.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"32 ","pages":"Article 105406"},"PeriodicalIF":4.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928911","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":"Glycine N-acyltransferase deficiency in sensory neurons suppresses osteoarthritis pain","authors":"Lei Wang ,&nbsp;Junlong Luo ,&nbsp;Zengwei Mao ,&nbsp;Wenjing Zhao ,&nbsp;Shuai Du ,&nbsp;Yujie Zhang ,&nbsp;Qingzhuo Cui ,&nbsp;Hui Liu ,&nbsp;Bo Yang ,&nbsp;Rong Zheng ,&nbsp;Shuaibing Guo ,&nbsp;Yunshuang Wang ,&nbsp;Xiulin Huo ,&nbsp;Tianyun Zhang ,&nbsp;Fan Zhang ,&nbsp;Han Li","doi":"10.1016/j.jpain.2025.105408","DOIUrl":"10.1016/j.jpain.2025.105408","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a degenerative joint disease characterized by chronic pain, which profoundly impacts patients’ quality of life. The analgesic treatment for OA is an urgent clinical problem to be addressed. Glycine <em>N</em>-acyltransferase (GLYAT) is an enzyme that plays a vital role in facilitating biochemical reactions through the catalysis of glycine conjugation. Here, this study constructed an OA pain model using sodium monoiodoacetate (MIA) and discovered a significant upregulation of GLYAT in the dorsal root ganglia (DRG) of OA mice through transcriptomic sequencing. This study demonstrates GLYAT is predominantly expressed in DRG neurons and co-localizes with CGRP, IB4, or NF200-positive neurons. Overexpression of GLYAT leads to the development of prominent mechanical and thermal hyperalgesia. Loss of GLYAT effectively alleviates pain-like behaviors in OA mice without impairing baseline nociception and tactile sensations. Subsequent investigations show that GLYAT overexpression disrupts the redox balance and increases reactive oxygen species (ROS) levels within DRG neurons, leading to the upregulation of transient receptor potential vanilloid 1 (TRPV1) channel. Furthermore, ROS clearance or TRPV1 blockade in GLYAT-overexpressing mice significantly increased mechanical withdrawal threshold and thermal withdrawal latency. Collectively, these results demonstrate that GLYAT regulates OA pain by increasing ROS production and TRPV1 channel expression. This work also suggests the potential of GLYAT as a novel target for analgesic therapies.</div></div><div><h3>Perspective</h3><div>This article highlights the innovative finding of increased GLYAT levels in DRG neurons of the mice with OA pain. The role of GLYAT in regulating ROS and TRPV1 levels suggests its potential as a target for managing OA pain.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"33 ","pages":"Article 105408"},"PeriodicalIF":4.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055161","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":"Truncated TrkB: The predominant TrkB isoform in nociceptors","authors":"Jaclyn Merlo ,&nbsp;Fang-Mei Chang ,&nbsp;Michael Tran ,&nbsp;Jessie Alfaro ,&nbsp;Tarek Ibrahim ,&nbsp;Ping Wu ,&nbsp;Shivani Ruparel","doi":"10.1016/j.jpain.2025.105409","DOIUrl":"10.1016/j.jpain.2025.105409","url":null,"abstract":"<div><div>Truncated TrkB (TrkBT1), traditionally considered a dominant-negative regulator of full-length TrkB (TrkBTK+), remains poorly understood in peripheral sensory neurons, particularly nociceptors. Furthermore, sensory neuronal TrkB expression and function has been traditionally associated with non-nociceptive neurons, particularly Aδ low-threshold mechanoreceptors. This study challenges prevailing assumptions by demonstrating that TrkBT1 is the predominant TrkB isoform expressed in trigeminal sensory neurons and plays a functional role in modulating neuronal activity. We demonstrate that TrkBT1 is the predominant isoform expressed in trigeminal nociceptors, identified by markers such as TRPV1, TRPA1, TRPM8 and 5HT3A, as well as non-nociceptors, while the full-length isoform (TrkBTK+) is restricted to non-nociceptive subpopulation. Functionally, we show that acute application of BDNF induces modest calcium influx in nociceptors and prolonged BDNF exposure significantly potentiates capsaicin-induced calcium influx, an effect blocked by the TrkB-specific antagonist ANA12. Additionally, BDNF also promotes survival of both nociceptive and non-nociceptive neurons in culture, an effect dependent on TrkBT1 activity. Our data also reveal that ANA12 inhibits BDNF-mediated neuronal sensitization and survival in a concentration-dependent manner, implicating distinct TrkBT1 signaling pathways in these processes. Collectively, our findings redefine TrkBT1 as a functional modulator of trigeminal nociceptor activity rather than a passive regulator of full-length TrkB. By uncovering its dual roles in nociceptor sensitization and survival, this study provides new insights into the molecular mechanisms of BDNF/TrkB signaling in pain. Future work evaluating the role of TrkBT1 in sensory biology could offer new perspectives on how this receptor contributes to neuronal function and plasticity during chronic pain conditions.</div></div><div><h3>Perspective</h3><div>This study redefines TrkB-T1 as a functional modulator of trigeminal nociceptors, challenging the assumption that full-length TrkB is the primary isoform. It reveals TrkB-T1′s role in BDNF-induced sensitization and survival, providing new insights into BDNF/TrkB signaling in pain and potential therapeutic interventions.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"31 ","pages":"Article 105409"},"PeriodicalIF":4.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885546","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":"Beyond pain intensity: Validating single-item pain bothersomeness measures","authors":"Karlyn A. Edwards PhD ,&nbsp;Dokyoung Sophia You PhD ,&nbsp;Edward W. Lannon PhD ,&nbsp;Troy C. Dildine PhD ,&nbsp;Beth D. Darnall PhD ,&nbsp;Sean C. Mackey MD, PhD","doi":"10.1016/j.jpain.2025.105395","DOIUrl":"10.1016/j.jpain.2025.105395","url":null,"abstract":"<div><div>Chronic pain is a complex and multifaceted health condition, rendering pain intensity alone insufficient for comprehensively understanding the impact of pain. Pain bothersomeness scales have been developed to measure pain’s impact on life, however lack adequate validation. Our study examines the validity of two single-item measures (5-point and 11-point response scales) for pain bothersomeness. We collected data from 633 treatment-seeking adults with mixed-etiology chronic pain. Pearson correlations were conducted to examine the relationships between each pain bothersomeness item and 20 general and pain-related functioning measures. ANOVAs examined the ability of pain bothersomeness scores to discriminate between eight groupings based on general and pain-related functioning. Linear regressions analyzed pain bothersomeness as a predictor of 14 measures of general and pain-related functioning three months later. Both pain bothersomeness items correlated significantly with 19 functioning measures and discriminated between eight groupings. Controlling for covariates, both items were consistently predictive of worse pain interference (Total adj r² =.34), pain catastrophizing (Total adj r² =.21–.22), depression (Total adj r² =.25–.26), and satisfaction with social roles (Total adj r² =.13–.16) three months later. Both single-item pain bothersomeness items demonstrated consistent concurrent, discriminant, and predictive validity. These low-burden assessments provide valuable information about patient functioning in clinical settings, suggesting their utility in improving chronic pain care.</div></div><div><h3>Perspective</h3><div>Both single-item pain bothersomeness measures demonstrated consistent concurrent and discriminant validity. Both items predicted worse pain interference, pain catastrophizing, depression, and social functioning 3-months later.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"31 ","pages":"Article 105395"},"PeriodicalIF":4.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834505","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":"Systematic review of autistic representation in the treatment literature for pediatric chronic pain.","authors":"Katelynn E Boerner, Colleen Pawliuk, Aishwarya Heran, Bethany Donaghy, David Moore, Kai Leong, Hemakumar Devan, Tim F Oberlander","doi":"10.1016/j.jpain.2025.105390","DOIUrl":"10.1016/j.jpain.2025.105390","url":null,"abstract":"<p><p>Chronic pain disproportionately affects autistic children and young people, yet they are underrepresented in pain research. Research on psychological, physical, and pharmacological therapies for other conditions suggests modifications are required to ensure treatment accessibility and efficacy for autistic individuals. However, no such evidence base has been synthesized in pediatric pain. The aim of this review was to (1) review existing \"gold-standard\" treatment literature for pediatric chronic pain to determine the representation of autistic participants, and (2) review literature on treatment of chronic pain specifically in autistic children and young people to describe the current evidence landscape and identify next directions for research. 16.7% (12/72) of randomized controlled trials included in Cochrane reviews of interventions for pediatric chronic pain explicitly excluded youth with a developmental delay/disability, of which only 8.3% specifically named autism. However, 52.8% of Cochrane-included trials had criteria or protocols which may have disproportionately impacted autistic participants, such as excluding intellectual disability, psychiatric conditions, medical conditions, and/or requiring participants to communicate verbally. Twenty-nine studies of treating chronic pain in autistic children and young people were identified, of which the majority were case reports (k = 27, 93%) with large variation in pain condition, intervention applied, and outcomes measured. Given the high prevalence of chronic pain in autistic children and young people, there is an ethical imperative to ensure their representation in intervention trials, co-develop interventions that address the specific needs of autistic individuals who live with pediatric chronic pain, and to increase accessibility in chronic pain research more broadly. REGISTRATION: PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=491423 registered March 19 2024. Open Science Framework: https://osf.io/8na64/ registered December 18, 2023 PERSPECTIVE: Autistic children and young people (CYP) are not represented in reviews of chronic pain treatments, and the literature on treating chronic pain specifically in this population is so variable no clear conclusions can be drawn. Efforts to increase accessibility of chronic pain interventions and research for autistic CYP is needed.</p>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":" ","pages":"105390"},"PeriodicalIF":4.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047381","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":"The effect of online social support on experimental pain","authors":"Kai Karos ,&nbsp;Michel Meulders ,&nbsp;Imke Courtois ,&nbsp;Lisa De Wit ,&nbsp;Ali Gholamrezaei ,&nbsp;Ann Meulders","doi":"10.1016/j.jpain.2025.105392","DOIUrl":"10.1016/j.jpain.2025.105392","url":null,"abstract":"<div><div>Ample evidence shows that in-person social support can alleviate both acute and chronic pain complaints. However, less is known about the effectiveness of online social support. Disparities in availability of and access to in-person social support could make online social support a promising and cost-effective alternative. To this end we aimed to compare the effects of online versus in-person social support on pain induced with a cold-pressor task (CPT). Specifically, 62 pain-free female participants immersed their feet in cold water (1) alone, (2) in the physical presence of a supportive other, (3) while chatting with the supportive other online, and (4) while chatting online with a stranger, in a randomized order. We assessed self-reported pain intensity, pain unpleasantness, and threat value of pain, as well as pain tolerance (i.e. immersion time) and heart rate. Overall, pain intensity and unpleasantness ratings were higher in the alone condition compared to the other conditions. A similar pattern was found in pain tolerance, but the differences were not statistically significant. Heart rate increased during the CPT but was highest in the in-person support condition. Moreover, recovery after cold water immersion was slower in the alone condition compared to the other conditions. In sum, interaction with a supportive other or a stranger, be it online or in-person, led to a reduction in acute pain compared to being alone. This study presents initial evidence that online interaction with others might be an effective alternative to in-person social support in order to reduce acute pain in women.</div></div><div><h3>Perspective</h3><div>Online and in-person social support were equally effective in reducing acute experimental cold-pressor pain compared to being alone. There was no difference between social support from strangers or a supportive other.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"31 ","pages":"Article 105392"},"PeriodicalIF":4.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848017","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":"Pre-sleep alpha brain entrainment by audio or visual stimulation for chronic widespread pain and sleep disturbance: A randomised crossover feasibility trial","authors":"SJ Halpin ,&nbsp;L Xing ,&nbsp;DC Greenwood ,&nbsp;NKY Tang ,&nbsp;NJ Trujillo-Barreto ,&nbsp;CA Brown ,&nbsp;AKP Jones ,&nbsp;RJ O'Connor ,&nbsp;AJ Casson ,&nbsp;M Sivan","doi":"10.1016/j.jpain.2025.105393","DOIUrl":"10.1016/j.jpain.2025.105393","url":null,"abstract":"<div><div>Home-based neuromodulation is a potentially scalable option to assist with management of chronic widespread pain. Since sleep disturbance is closely interrelated with chronic pain, especially in conditions such as fibromyalgia, targeting symptoms pre-sleep could enhance treatment efficacy. Alpha entrainment is a neuromodulatory technique to improve pain which can be applied via a smartphone programme using 10 Hz stimulation through flickering light or binaural beats. The aim of this study was to assess feasibility, mechanistic effects on alpha spectral power during pre-sleep entrainment and indicate the potential effect on symptoms. Adults with fibromyalgia participated in two weeks of active and sham stimulation at home pre-sleep in a randomised, balanced sequence, with a one-week washout, in a two-period crossover design. Sham stimulation was non-rhythmic but otherwise perceptually similar, and participants and experimenters were masked to sequence. Effect of stimulation was assessed with daily symptom and sleep diary, nightly wearable EEG monitoring (Dreem 3 headband) and actigraphy. Alpha spectral power was enhanced during active compared to sham stimulation, substantiating the entrainment effect under pre-sleep, home based conditions. Pain at night (0–10 scale) decreased with active stimulation compared to sham: difference −0.53 (95 % CI −0.81 to −0.25, P&lt;0.001). Sleep quality (0–5 scale) improved with active stimulation compared to sham: difference +0.39 (95 % CI 0.15 to 0.64, P= 0.002). Pre-sleep sensory alpha entrainment with home-based EEG monitoring in fibromyalgia is feasible with potentially helpful effects on pain and sleep without significant unwanted effects. Longer duration study in larger trials is warranted.</div></div><div><h3>ClinicalTrials.gov registration ID</h3><div>NCT05699837</div></div><div><h3>Perspective</h3><div>This study applies a non-invasive pre-sleep neuromodulatory technique in individuals with fibromyalgia. It demonstrates the feasibility of the approach, verifies the mechanism of sensory alpha entrainment in this real-life environment and indicates self-reported improvements to pain and sleep quality compared to a sham stimulation. These findings can help refine interventions and design larger trials.</div></div><div><h3>Data availability</h3><div>Data will be made available on reasonable request.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"31 ","pages":"Article 105393"},"PeriodicalIF":4.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839568","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":"A Triple combination formulation of an HDAC inhibitor treats chronic pain in rodent spared nerve injury model","authors":"Maria V. Centeno ,&nbsp;Md. Suhail Alam ,&nbsp;Kasturi Haldar ,&nbsp;A. Vania Apkarian","doi":"10.1016/j.jpain.2025.105396","DOIUrl":"10.1016/j.jpain.2025.105396","url":null,"abstract":"<div><div>Histone deacetylase inhibitors (HDACi) that modulate epigenetic regulation and are approved for treating rare cancers have, in disease models, also been shown to mitigate neurological conditions, including chronic pain. They are of interest as non-opioid treatments, but achieving long-term efficacy with limited dosing has remained elusive. Here we employ a triple combination formulation (TCF) that includes the pan-HDAC vorinostat (Vo) administered at its FDA-approved daily dosage of 50 mg/Kg, along with the caging agent 2-hydroxypropyl-β-cyclodextrin (HPBCD) and polyethylene glycol (PEG). This formulation enhances plasma and brain exposure of Vo in mice and rat models and shows specific activity in the spared nerve injury (SNI) model of chronic neuropathic pain. TCF (but not HPBCD and PEG) decreased mechanical allodynia for 4 weeks without antagonizing weight, anxiety, or mobility. This was achieved at less than 1% of the total dose of Vo approved for 4 weeks of tumor treatment, decreased RNA levels of two major inflammatory markers (CD11b and GFAP), and reduced proliferation of microglia in the ipsilateral (but not contralateral) spinal cord. A single TCF injection was sufficient for 3–4 weeks of efficacy. Pharmacodynamics suggested pain relief was sustained for weeks after Vo elimination. Doubling Vo in a single TCF injection tripled the response amplitude and remained effective for &gt; 2 months in male rats. Together, these data suggest that the TCF enables single-dose effectiveness with extended action, reduces long-term HDACi dosage, and presents excellent potential to develop as a non-opioid treatment option for chronic pain.</div></div><div><h3>Perspective</h3><div>An epigenetic drug formulation (TCF) tested in rat and mouse chronic neuropathic pain models shows adequate and persistent pain relief, engaging spinal cord inflammatory mechanisms.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"31 ","pages":"Article 105396"},"PeriodicalIF":4.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834506","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}