Neurobiology of Pain最新文献

{"title":"Glutamate levels in the cingulate cortex are associated with objective markers of pain sensitivity by way of pre-stimulus alpha band oscillations","authors":"Paulina S. Scheuren ,&nbsp;Oscar Ortiz ,&nbsp;Lukas D. Linde ,&nbsp;Cassandra M. Choles ,&nbsp;Erin L. MacMillan ,&nbsp;John L.K. Kramer","doi":"10.1016/j.ynpai.2025.100204","DOIUrl":"10.1016/j.ynpai.2025.100204","url":null,"abstract":"<div><div>Pain varies substantially from one individual to the next. Understanding the role of brain function in variations to pain, both in health and disease, represents an important steppingstone towards individualized pain management. This study aimed to investigate the association between glutamate levels and pain sensitivity, and whether this is mediated by alpha band oscillations. Fifty-one healthy individuals were recruited for this study. Laser evoked potentials (LEPs) and pain ratings were recorded in response to 20 stimuli applied at 4 different intensities (2.75, 3, 3.25, 3.5 J) to the right volar forearm. Brain alpha band oscillations (7–13 Hz) were extracted from the pre-stimulus timeframe (−1000 ms to −100 ms). Single-voxel magnetic resonance spectroscopy data were collected to estimate regional differences in glutamate levels across the anterior (ACC) and posterior cingulate cortex (PCC) using a 3 T scanner. Cluster analysis of LEPs revealed two clusters (high vs. low N2P2 amplitudes). Glutamate levels were reduced in the PCC versus ACC in the ‘low LEP’ (t = 3.6, p &lt; 0.001), but not ‘high LEP’ cluster (t = 1.08, p = 0.285). Causal mediation analysis revealed that the effect of ACC:PCC glutamate ratio on LEP peak-to-peak amplitudes was mediated via pre-stimulus alpha band oscillations (β_indirect = −25.6(−63.9, −2.4), p = 0.034]. This study indicates that glutamate levels across the cingulate cortexshape subsequent brain responses to noxious input, and that this is mediated by pre-stimulus alpha band oscillations. Both brain metabolites and oscillations thus likely play a vital role in individual variabilities in experimental pain.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100204"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The RNA-binding protein CELF4 is a negative regulator of sensory neuron excitability and mechanical and heat behavioral sensitivity","authors":"Madison G. Mueth ,&nbsp;Peter Neufeld ,&nbsp;Merilla Michael ,&nbsp;Aidan McGrath-Conwell ,&nbsp;Eliza Grlickova-Duzevik ,&nbsp;Tamara King ,&nbsp;Christoph Straub ,&nbsp;Benjamin J. Harrison","doi":"10.1016/j.ynpai.2025.100184","DOIUrl":"10.1016/j.ynpai.2025.100184","url":null,"abstract":"<div><div>RNA-binding proteins (RBPs) regulate gene function by controlling RNA processing, transport, stability, and translation. Recent mechanistic and pre-clinical studies demonstrate that nociceptive sensitivity and plasticity are regulated by RNA-protein interactions. Investigating RBP function in sensory neurons may reveal new strategies to modulate nociceptor excitability and/or sensitivity and improve our understanding of mechanisms that contribute to pain chronification. We previously identified the RBP CUG triplet repeat binding protein (<u>C</u>UGBP) embryonic lethal abnormal vision (<u>E</u>lav)-<u>l</u>ike <u>f</u>amily member <u>4</u> (CELF4) as co-expressed with nociceptive markers in mouse, rat, and macaque dorsal root ganglia (DRG). In the central nervous system, CELF4 limits the translation of synaptic mRNAs, and loss of CELF4 results in hyperexcitability of excitatory neurons and spontaneous seizures. To elucidate the function of CELF4 in sensory neurons, we employed conditional knockout (KO) mouse models, with <em>Celf4</em> deleted selectively in populations of adult DRG neurons. Using patch-clamp electrophysiology in acutely dissociated neurons, we observed a striking reduction in rheobase and hyperexcitability of capsaicin-sensitive adult <em>Celf4</em> KO DRG neurons compared to controls. Behavioral assessments revealed that these mice display robust mechanical and thermal hypersensitivity and an exaggerated evoked hypersensitivity response to intraplantar capsaicin and nerve growth factor. These studies reveal that the translational regulator CELF4 is a powerful negative regulator of sensory neuron excitability and sensory thresholds to heat and mechanical stimuli resulting in thermal and mechanical hypersensitivity in uninjured mice and exacerbating hypersensitivity in injured mice. These findings elucidate a novel mechanism for modulating sensory neuron excitability with high specificity to putative nociceptors.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100184"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating microRNAs differentiate nociceptive and nociplastic pain: An exploratory study","authors":"Hiroyuki Nishie ,&nbsp;Hideki Nakatsuka ,&nbsp;Kazunori Iwasa ,&nbsp;Yuka Sakuta ,&nbsp;Yuichiro Toda ,&nbsp;Shigeru Mitani ,&nbsp;Takeshi Nagasaka","doi":"10.1016/j.ynpai.2025.100191","DOIUrl":"10.1016/j.ynpai.2025.100191","url":null,"abstract":"<div><h3>Background</h3><div>Nociceptive and nociplastic pain arise from distinct biological mechanisms, yet their differentiation remains clinically challenging. Circulating microRNAs (miRNAs) are promising candidates for objective, mechanism-based pain classification.</div></div><div><h3>Objective</h3><div>To explore whether specific circulating miRNAs can differentiate nociceptive pain in patients with hip osteoarthritis (HO) from nociplastic pain in patients with chronic primary pain (CPP), and to assess their relationship with clinical and psychological outcomes.</div></div><div><h3>Methods</h3><div>In this exploratory, single-center study, plasma samples were collected from patients with HO (n = 13), CPP (n = 11), and healthy controls (n = 7). Microarray screening identified candidate miRNAs, which were validated via real-time PCR. Pain intensity (NRS), disability (PDAS), quality of life (EQ-5D), and psychological factors (PCS, PSEQ, TSK-11, PHQ-9) were assessed. Classification accuracy was evaluated using decision tree modeling and ROC analysis.</div></div><div><h3>Results</h3><div><em>Let-7a</em>, <em>miR-26a</em>, and <em>miR-16</em> showed distinct expression profiles and contributed to a predictive model with strong performance (<em>R²</em> = 0.677; AUC &gt; 0.94). <em>Let-7a</em> expression was associated with structural joint changes in HO but not subjective pain ratings. <em>MiR-26a</em> correlated with cognitive-affective pain traits in CPP, and <em>miR-16</em> decreased following CBT, suggesting a role in treatment-related neuroplasticity. <em>MiR-126</em> and <em>miR-146a</em> were linked to reductions in pain intensity post-surgery in the HO group. QOL improved in HO, while psychological factors remained prominent in CPP.</div></div><div><h3>Conclusions</h3><div>This pilot study suggests that circulating miRNAs may aid in differentiating nociceptive and nociplastic pain mechanisms and tracking treatment effects. While preliminary, these findings support the potential utility of miRNA-based biomarkers in precision pain diagnostics and personalized management strategies.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100191"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"R and S enantiomers of CBD3063, a CaV2.2 N-type calcium channel modulator, alleviate capsaicin-induced inflammatory pain","authors":"Santiago Loya-López ,&nbsp;Erick J. Rodríguez-Palma ,&nbsp;Aida Calderón-Rivera ,&nbsp;Kimberly Gomez ,&nbsp;Samantha Perez-Miller ,&nbsp;Rajesh Khanna","doi":"10.1016/j.ynpai.2025.100185","DOIUrl":"10.1016/j.ynpai.2025.100185","url":null,"abstract":"<div><div>N-type voltage-gated calcium channels (Ca_V2.2) play a pivotal role in pain signaling, rendering them promising targets for pain treatment. However, direct blockers of Ca_V2.2 have demonstrated limited efficacy due to adverse side effects and inadequate blood–brain barrier penetration. In previous work, we developed CBD3063, a small molecule peptidomimetic that disrupts the Ca_V2.2-CRMP2 (collapsin response mediator protein 2) interaction, resulting in a reduction of Ca_V2.2 currents and pain relief without side effects. In this study, we investigated the individual contributions of the (R) and (S) enantiomers of CBD3063 to its pharmacological effects. Whole-cell patch-clamp recordings from mouse dorsal root ganglion (DRG) sensory neurons indicated that the (S) and (R) enantiomers reduced Ca_V2.2 currents. Furthermore, racemic CBD3063 and the (S) enantiomer exhibited antinociceptive effects in the capsaicin-induced model of inflammatory pain. These findings suggest that the (S) and (R) enantiomers contribute to the therapeutic effects of CBD3063.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100185"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FL/FLT3 signaling enhances mechanical pain hypersensitivity through Interleukin-1 beta (IL-1β) in male mice","authors":"Corinne Sonrier ,&nbsp;Chamroen Sar ,&nbsp;Ivo Melo ,&nbsp;Lucie Dioufoulet ,&nbsp;Gabriel V. Lucena-Silva ,&nbsp;Sylvie Mallié ,&nbsp;Juliette Bertin ,&nbsp;Jean-Philippe Leyris ,&nbsp;Fabrice Ango ,&nbsp;Thiago M. Cunha ,&nbsp;Hamid Moha ou Maati ,&nbsp;Jean Valmier ,&nbsp;Cyril Rivat ,&nbsp;Ilana Méchaly","doi":"10.1016/j.ynpai.2025.100202","DOIUrl":"10.1016/j.ynpai.2025.100202","url":null,"abstract":"<div><div>Fms-like tyrosine kinase 3 (FLT3) plays a critical role in chronic pain through its ligand FL, a cytokine that triggers mechanical pain hypersensitivity. However, the underlying molecular mechanisms remain unclear. Here, we investigate the potential interplay between FL and IL-1β a key cytokine in DRG neurons sensitization and mechanical hyperalgesia through both <em>in vitro</em> and <em>in vivo</em> approaches. ELISA assays reveal that intrathecal FL administration significantly increases IL-1β protein levels in both the DRG and dorsal spinal cord of mice, by four hours post-injection. Using video microscopy and [Ca²⁺] ₁ fluorescence imaging in primary DRG neuron cultures, we demonstrate that FL potentiation of TRPV1 receptor responses to capsaicin is partially mediated by IL-1β signalling, as evidenced by a significant reduction in this potentiation in the presence of the IL-1 receptor antagonist, IL-1Ra. Furthermore, FLT3-driven acute mechanical pain hypersensitivity <em>in vivo</em> is reduced both by prior administration of IL-1Ra and in IL-1 receptor knockout mice. Importantly, IL-1β-induced mechanical pain hypersensitivity remains independent of FLT3 signalling as shown in <em>Flt3</em> knockout mice. Collectively our findings expand the understanding of neuro-immune interactions by demonstrating a potential functional link between FL/FLT3 and IL-1β/IL-1R signalling in nociceptive processing.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100202"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The contribution of clock genes BMAL1 and PER2 in osteoarthritis-associated pain","authors":"Erick J. Rodríguez-Palma ,&nbsp;Santiago Loya-Lopez ,&nbsp;Kyle Allen ,&nbsp;Yenisel Cruz-Almeida ,&nbsp;Rajesh Khanna","doi":"10.1016/j.ynpai.2024.100177","DOIUrl":"10.1016/j.ynpai.2024.100177","url":null,"abstract":"<div><div>Joint pain is the primary symptom of osteoarthritis (OA) and the main motivator for patients to seek medical care. OA-related pain significantly restricts joint function and diminishes quality of life. Despite the availability of various pain-relieving medications for OA, current treatment strategies often fall short in delivering adequate pain relief. Furthermore, long-term use of pain medications for OA management is frequently linked with notable side effects and toxicities, suggesting the need to explore new potential targets to treat pain in OA patients. In this context, clock genes, particularly brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (BMAL1) and period circadian protein homolog 2 (PER2), known for their role in circadian rhythms, represent promising opportunities for pharmacological interventions due to their involvement in both the development and maintenance of OA pain. While BMAL1 and PER2 have been extensively studied in neuropathic and inflammatory pain, their specific contributions to OA pain remain less clear, demanding further investigation. This narrative review aims to synthesize the relationship between OA pain and the BMAL1 and PER2 signaling pathways, ultimately exploring the potential therapeutic role of clock genes in addressing this challenging condition.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"17 ","pages":"Article 100177"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030301","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":"Glial activation and nociceptive neuropeptide elevation associated with the development of chronic post-traumatic headache following repetitive blast exposure","authors":"Amirah Wright ,&nbsp;Susan F. Murphy ,&nbsp;Pamela J. VandeVord","doi":"10.1016/j.ynpai.2024.100178","DOIUrl":"10.1016/j.ynpai.2024.100178","url":null,"abstract":"<div><div>Chronic headaches and pain are prevalent in those who are exposure to blast events, yet there is a gap in fundamental data that identifies the pathological mechanism for the chronification of pain. Blast-related post-traumatic headaches (PTH) are understudied and chronic pain behaviors in preclinical models can be vital to help elucidate PTH mechanisms. The descending pain modulatory system controls pain perception and involves<!--> <!-->specific brain regions such as the cortex, thalamus, pons, and medulla. In this study, male rats were exposed to repeated blast events to induce traumatic brain injury (bTBI) and subsequently assessed for the development of PTH by testing for chronic pain behaviors and examining the neuropathology of the descending pain pathway. The results demonstrated that facial hypersensitivity developed as early as week two following bTBI and persisted throughout the study (12 weeks). Depressive-like behaviors were observed at 12 weeks following bTBI, and these behaviors were associated with neuropathologies such as microglia ramification and neuropeptide elevation (Calcitonin Gene-Related Peptide, CGRP; Substance P, SP). Overall, these findings support the hypothesis that bTBI causes the activation of microglia and elevation of neuropeptides, which contribute to the development of chronic PTH behaviors.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"17 ","pages":"Article 100178"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030299","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":"Critical reflections on medication overuse headache in patients with migraine: An unsolved riddle in nociception","authors":"Alberto Chiarugi ,&nbsp;Daniela Buonvicino","doi":"10.1016/j.ynpai.2025.100179","DOIUrl":"10.1016/j.ynpai.2025.100179","url":null,"abstract":"<div><div>Migraine chronification very frequently exposes patients to the inevitable risk of excessive symptomatic intake that, in turn, prompts development of medication overuse headache (MOH). The latter further compromises headache severity establishing a vicious cycle of symptomatic intake and relapsing head pain that critically worsens the overall clinical status of patients. A great deal of attention has been focused on MOH pathogenesis, and thanks to preclinical and clinical studies knowledge about this disorder is now remarkably advanced. Still, some open questions remain regarding issues related to the neurobiology and neurochemistry underpinning pain chronification in MOH patients, as well as the remedies capable of interrupting pronociceptive cephalic sensitization and drug overuse. Here, a critical reappraisal of these issues is provided in an attempt to gain deeper insight and promote debate on a pain disorder that still represents a conundrum in the field of nociception.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"17 ","pages":"Article 100179"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427655","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":"Targeting Nav1.7 and Nav1.8 with a PIKfyve inhibitor to reverse inflammatory and neuropathic pain","authors":"Erick J. Rodríguez-Palma ,&nbsp;Santiago Loya-Lopez ,&nbsp;Sophia M. Min ,&nbsp;Aida Calderon-Rivera ,&nbsp;Kimberly Gomez ,&nbsp;Rajesh Khanna ,&nbsp;Alison D. Axtman","doi":"10.1016/j.ynpai.2024.100174","DOIUrl":"10.1016/j.ynpai.2024.100174","url":null,"abstract":"<div><div>PIKfyve (1-phosphatidylinositol 3-phosphate 5-kinase), a lipid kinase, plays an important role in generating phosphatidylinositol (3,5)-bisphosphate (PI(3,5)P₂). SGC-PIKFYVE-1, a potent and selective inhibitor of PIKfyve, has been used as a chemical probe to explore pathways dependent on PIKfyve activity. Based on reported changes in membrane dynamics and ion transport in response to PIKfyve inhibition, we hypothesized that pharmacological inhibition of PIKfyve could modulate pain. Acute treatment with SGC-PIKFYVE-1 (10 µM) inhibited voltage-gated sodium currents through the inhibition of Na_v1.7 and Na_v1.8 channels, without affecting voltage-gated calcium or potassium currents in sensory neurons. Additionally, systemic administration of SGC-PIKFYVE-1 (30 mg/kg) alleviated mechanical and cold sensitivity induced by neuropathic or inflammatory pain in both male and female mice, without causing motor impairments. Although other functions of PIKfyve are well characterized, its role in inhibiting chronic pain has not been fully elucidated. Our study provides proof-of-concept for this alternative approach to pain management. Collectively, these results highlight the inhibitory effects of PIKfyve as a promising avenue for further exploration in chronic pain treatment.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"17 ","pages":"Article 100174"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886485","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":"Evidence for glial reactivity using positron-emission tomography imaging of translocator Protein-18 kD [TSPO] in both sham and nerve-injured rats in a preclinical model of orofacial neuropathic pain","authors":"Gaelle M. Emvalomenos ,&nbsp;James W.M. Kang ,&nbsp;Sabrina Salberg ,&nbsp;Crystal Li ,&nbsp;Bianca Jupp ,&nbsp;Matthew Long ,&nbsp;Mohammad B. Haskali ,&nbsp;Sunil Kellapatha ,&nbsp;OIivia I. Davanzo ,&nbsp;Hyunsol Lim ,&nbsp;Richelle Mychasiuk ,&nbsp;Kevin A. Keay ,&nbsp;Luke A. Henderson","doi":"10.1016/j.ynpai.2024.100175","DOIUrl":"10.1016/j.ynpai.2024.100175","url":null,"abstract":"<div><div>Chronic neuropathic pain is a debilitating condition that results from damage to the nervous system. Current treatments are largely ineffective, with limited understanding of the underlying mechanisms hindering development of effective treatments. Preclinical models of neuropathic pain have revealed that non-neural changes are important for the development of neuropathic pain, although these data are derived almost exclusively from post-mortem histological analyses. Although these static snapshots have provided valuable data, they cannot provide insights into non-neural cell changes that could be also assessed in human patients with chronic pain. In this study we used translocator protein 18 kDa (TSPO) PET imaging with [¹⁸F]PBR06 to visualise in-vivo, the activity of macrophages and microglia in a rodent preclinical model of trigeminal neuropathic pain. Using chronic constriction injury of the infraorbital nerve (ION-CCI) we compared temporal changes in TSPO binding in male rats, prior to, and up to 28 days after ION-CCI compared with both sham-injured and naïve counterparts. Unexpectedly, we found significant increases in TSPO signal in both ION-CCI and sham-injured rats within the trigeminal ganglion, spinal trigeminal nucleus and paratrigeminal nucleus during the initial phase following surgery and/or nerve injury. This increased TSPO binding returned to control levels by day 28. Qualitative histological appraisal of macrophage accumulation and glial reactivity in both ION-CCI and sham-injured rats indicated macrophage accumulation in the trigeminal ganglion and microglial reactivity in the brainstem trigeminal complex. These findings show, glial changes in the peripheral nerve and brain in both nerve-injured and sham-injured rats in a preclinical model of neuropathic pain which provides a platform for translation into human patients.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"17 ","pages":"Article 100175"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933485","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}