Biology subjects

Dussor, G.

Publications and source records attributed to Dussor, G..

At least 19 recordsLinked to original sources

bioRxiv2026

History of opioid use disorder correlates with altered neuroimmune signatures in the human dorsal root ganglia

Understanding mechanisms for the negative reinforcing effects of opioids are fundamental to improving patient care. Using human dorsal root ganglia (DRG) from donors with and without opioid use disorder (OUD), we set out to examine functional and molecular correlates of chronic opioid use. At a molecular level, we detected disrupted immune signatures throughout cells in the peripheral nervous system (PNS), spanning glial-neuroimmune interactions to changes in non-neuronal senescence. At the physiological level these changes are paired with sensitization of DRG sensory neurons. Our findings reveal a neuro-inflammatory state in the PNS of individuals with OUD. Targeting therapeutics towards these PNS-based mechanisms could be an approach to alleviating the negative reinforcing effects of opioids.

neuroscience↗

bioRxiv2026

Chronic lower limb pain is not associated with a loss of inhibitory neurons in the human lumbar spinal dorsal horn

The spinal dorsal horn is the primary processing site of nociceptive sensory input from the periphery. Excitatory spinal interneurons releasing glutamate can amplify this information before it is sent to the brain, whereas inhibitory neurons releasing GABA and/or glycine can suppress the outflow of nociceptive signals. An imbalance favoring excitation is thought to underlie certain aspects of chronic pain. Although rodent studies have identified spinal mechanisms underlying hyperalgesia and allodynia, little is known about the anatomical changes associated with chronic pain in the human spinal cord, a gap in knowledge we sought to address in this study. Using immunohistochemistry and in situ hybridization on lumbar spinal cord tissue recovered from organ donors, we characterized neuronal size and density across the human dorsal horn and confirmed the presence of the human equivalent of the lateral spinal nucleus in many individuals. Chronic lower limb pain was not associated with changes in neuronal density in the dorsal horn. Likewise, the ratio of excitatory (SLC17A6+) to inhibitory (PAX2+) neurons remained consistent across laminae for age, sex and chronic pain state, providing no evidence for selective loss of inhibitory neurons with chronic pain in humans. We found no differences in the size or density of the postsynaptic markers Homer1 and gephyrin between groups, suggesting glutamatergic and GABAergic postsynaptic sites remain structurally stable. These findings provide a thorough evaluation of cellular anatomy of the human dorsal horn and form a foundation for future studies investigating neuronal changes that may contribute to chronic pain in humans.

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bioRxiv2026

Antibiotics modulate activity of mouse and human dorsal root ganglia neurons

Antibiotics are among the most prescribed medications worldwide, yet their direct effects on eukaryotic tissues remain largely unexplored. Here, we used in vitro calcium imaging to determine if clinically relevant concentrations of common antibiotics alter mouse and human dorsal root ganglion (DRG) neuron activity. We found that {beta}-lactams, macrolides, and tetracyclines induce calcium flux in sensory neurons within minutes of application. Regardless of antibiotic class, neuronal responses depend on extracellular calcium entry. Pharmacological manipulations further revealed that cephalexin responses depend on TRPA1 activity whereas doxycycline responses require mitochondrial reactive oxygen species (ROS) production. These findings demonstrate that clinically relevant concentrations of antibiotics directly modulate sensory neuron activity through divergent mechanisms, thus expanding our current understanding of antibiotic side effects.

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bioRxiv2026

Progressive neurodegeneration in human dorsal root ganglion from diabetes to painful neuropathy

Diabetic painful neuropathy (DPN) is characterized by neuropathic pain accompanied by loss of sensory function. We hypothesized that neurodegeneration in the dorsal root ganglion (DRG) could underlie DPN progression. To address this question, we performed multi-omic evaluation on DRGs from otherwise healthy organ donors, donors with diabetes but no neuropathy, and donors with clinically diagnosed DPN. We discovered that the first stages of neurodegeneration begin early in diabetes before the onset of DPN, with Nageotte nodule formation accompanied by apoptotic gene expression and decreased proportion of specific populations of A-fibers in DPN with remodeling of non-neuronal cells. Our findings define DPN as a neurodegenerative disorder of the DRG, identify molecular markers of disease stage, and highlight the need for early intervention to prevent irreversible neurodegeneration.

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bioRxiv2025

A molecular map of the human spinal dorsal and ventral horn defines arrangement of neuronal types and glial sex differences

The spinal cord is the gateway for somatosensory and nociceptive information to the brain and a key locus for sensory-motor integration. Studies in mice have advanced our understanding of spinal cord circuitry, and transcriptomic studies have begun to characterize the human spinal cord; however, major gaps in knowledge persist. We conducted single-nucleus sequencing of lumbar spinal cord tissue from 11 adult organ donors and annotated spinal cord cell types with high resolution spatial transcriptomics. We identified 34 spatially and transcriptionally defined neuronal classes and detected sex-specific cell types and states across multiple glial populations. Electrophysiological recordings from dorsal horn neurons revealed firing patterns for neuronal subtypes and group I mGluR-dependent plasticity. Our work defines previously unknown aspects of human spinal cord molecular anatomy and physiology.

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bioRxiv2025

Enabling wider access to human molecular neuroscience research in pain: A simple preservation method for human dorsal root ganglion neurons in Hibernate A media

The use of human dorsal root ganglion (DRG) from organ donors opens the door for research into the molecular biology and physiology of human nociceptors; however, there are barriers to working with this tissue including logistical difficulties and limited access. We present an approach using Hibernate media to temporarily store either whole DRGs or dissociated DRG neurons prior to culturing and functional testing. Dissociation of DRGs following temporary storage (4-16hrs) in Hibernate media resulted in similar neuronal and immune cell yield as acutely dissociated DRGs. Neurons derived from DRGs stored in Hibernate media prior to dissociation exhibited similar electrophysiological properties and capsaicin responses as acutely dissociated DRG neurons. Similarly, neurons from acutely dissociated DRGs stored in Hibernate media (>24hrs) and shipped to geographically distant laboratories produced neuronal cultures displaying comparable electrophysiological properties as acutely cultured neurons. This approach overcomes insurmountable logistical burdens and increases access to freshly recovered human DRGs.

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bioRxiv2025

Mycobacterium tuberculosis sulfolipid-1 (Sl-1) increases the excitability of mouse and human TRPV1-positive sensory neurons in a YM254890-reversible fashion

Cough is a hallmark sign of tuberculosis and key driver of transmission. While traditionally attributed to host-driven inflammation, we previously demonstrated that Mycobacterium tuberculosis lipid extract (Mtb extract) and its component sulfolipid-1 (SL-1) directly activate nociceptive neurons to induce cough in guinea pigs. However, the cellular mechanisms by which Mtb extract and SL-1 modulate nociceptive sensory neurons remain incompletely understood. Here, we show that Mtb extract enhances action potential (AP) generation in mouse nodose nociceptors via an SL-1-dependent mechanism. Using calcium imaging, we found that Mtb extract and SL-1 increased intracellular Ca{superscript 2} signals in TRPV1 neurons from both mouse nodose and human dorsal root ganglia (hDRG). These Ca{superscript 2} signals were attenuated by the Gq/11 pathway inhibitor YM254890, even in the absence of extracellular Ca{superscript 2}, suggesting involvement of intracellular Ca{superscript 2} stores. Together, these findings indicate that SL-1 engages Gq/11-coupled pathways to sensitize nociceptors via intracellular Ca2+ release, providing mechanistic insight into tuberculosis-associated cough and potential targets for therapeutic intervention.

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bioRxiv2025

Suzetrigine (VX-548) exhibits activity-dependent effects on human dorsal root ganglion neurons

Non-selective antagonists of voltage-gated sodium channels (VGSCs) provide effective local analgesia, but systemic administration is fraught with unwanted cardiovascular and central nervous system toxicity. The development of antagonists targeting VGSCs preferentially expressed in peripheral neurons, such as NaV1.7, 1.8, and 1.9, could mitigate these risks. One such new small molecule that selectively inhibits NaV1.8, is orally bioavailable, and has recent FDA approval for the treatment of acute pain is suzetrigine (VX-548). Here we tested the effects of this agent on human dorsal root ganglion (hDRG) neurons obtained from either patients undergoing surgical thoracic vertebrectomy or from organ donors in parallel electrophysiology studies across 2 laboratories. Bath application of 10 nM suzetrigine abolished spontaneous discharges previously shown to be associated with on-going neuropathic pain within minutes. In contrast, suppression of discharges evoked by intracellular current injection required more prolonged application times. These results suggest that suzetrigine will likely show efficacy versus spontaneous pain but may have less robust effects on evoked or breakthrough pain.

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bioRxiv2025

Expansion of OSMR expression and signaling in the human dorsal root ganglion links OSM to neuropathic pain

RNA sequencing studies on human dorsal root ganglion (hDRG) from patients suffering from neuropathic pain show upregulation of OSM, linking this IL-6 family cytokine to pain disorders. In mice, however, OSM signaling causes itch behaviors through a direct effect on its cognate receptor expressed uniquely by pruriceptive sensory neurons. We hypothesized that an expansion in function of OSM-OSM receptor (OSMR) in sensory disorders in humans could be explained by species differences in receptor expression and signaling. Our in situ hybridization and immunohistochemical findings demonstrate broad expression of OSMR in DRG nociceptors and afferent fibers innervating the superficial and deep skin of humans. In patch-clamp electrophysiology, OSM directly activates human sensory neurons engaging MAPK signaling to promote action potential firing. Using CRISPR editing we show that OSM activation of MAPK signaling is dependent on OSMR and not LIFR in hDRG. Bulk, single-nuclei, and single-cell RNA-seq of OSM-treated hDRG cultures reveal expansive similarities in the transcriptomic signature observed in pain DRGs from neuropathic patients, indicating that OSM alone can orchestrate transcriptomic signatures associated with pain. We conclude that OSM-OSMR signaling via MAPKs is a critical signaling factor for DRG plasticity that may underlie neuropathic pain in patients.

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bioRxiv2025

Decreased KCC2 expression in the human spinal dorsal horn associated with chronic pain and long-term opioid use

Loss of GABAergic and glycinergic inhibitory efficacy in the spinal dorsal horn is associated with neuropathic pain and opioid-induced hyperalgesia in rodent models. Downregulation of the KCC2 chloride extrusion transporter is a key mechanism underlying this decreased inhibitory efficacy, but to-date there is no evidence supporting or opposing this hypothesis in humans. Here we demonstrate that KCC2 expression is decreased in superficial dorsal horn neurons of organ donors who died with a documented history of pain, or of long-term opioid use. We show profoundly decreased KCC2 dorsal horn membrane expression in a primary cohort associated with either chronic pain or opioid use, and in a replication cohort of mixed chronic pain and opioid use history. These results show that decreased dorsal horn inhibitory efficacy likely promotes chronic pain in humans and support the development of therapeutics augmenting KCC2 function as a treatment for chronic pain and opioid use disorders.

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bioRxiv2024

Profiling Human iPSC-Derived Sensory Neurons for Analgesic Drug Screening Using a Multi-Electrode Array

Chronic pain is a major global health issue, yet effective treatments are limited by poor translation from preclinical studies to humans. To address this, we developed a high-content screening (HCS) platform for analgesic discovery using hiPSC-derived nociceptors. These cells were cultured on multi-well micro-electrode arrays to monitor activity, achieving nearly 100% active electrodes by week two, maintaining stable activity for at least two weeks. After maturation (28 days), we exposed the nociceptors to various drugs, assessing their effects on neuronal activity, with excellent assay performance (Z values >0.5). Pharmacological tests showed responses to analgesic targets, including ion channels (Nav, Cav, Kv, TRPV1), neurotransmitter receptors (AMPAR, GABA-R), and kinase inhibitors (tyrosine, JAK1/2). Transcriptomic analysis confirmed the presence of these drug targets, although expression levels varied compared to primary human dorsal root ganglion cells. This HCS platform facilitates the rapid discovery of novel analgesics, reducing the risk of preclinical-to-human translation failure. MotivationChronic pain affects approximately 1.5 billion people worldwide, yet effective treatments remain elusive. A significant barrier to progress in analgesic drug discovery is the limited translation of preclinical findings to human clinical outcomes. Traditional rodent models, although widely used, often fail to accurately predict human responses, while human primary tissues are limited by scarcity, technical difficulties, and ethical concerns. Recent advancements have identified human induced pluripotent stem cell (hiPSC)-derived nociceptors as promising alternatives; however, current differentiation protocols produce cells with inconsistent and physiologically questionable phenotypes. To address these challenges, our study introduces a novel high-content screening (HCS) platform using hiPSC-derived nociceptors cultured on multi-well micro-electrode arrays (MEAs). The "Anatomic" protocol, used to generate these nociceptors, ensures cells with transcriptomic profiles closely matching human primary sensory neurons. Our platform achieves nearly 100% active electrode yield within two weeks and demonstrates sustained, stable activity over time. Additionally, robust Z factor analysis (exceeding 0.5) confirms the platforms reliability, while pharmacological validation establishes the functional expression of critical analgesic targets. This innovative approach improves both the efficiency and clinical relevance of analgesic drug screening, potentially bridging the translational gap between preclinical studies and human clinical trials, and offering new hope for effective pain management.

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bioRxiv2024

Nageotte nodules in human DRG reveal neurodegeneration in painful diabetic neuropathy

Diabetic neuropathy is frequently accompanied by pain and loss of sensation attributed to axonal dieback. We recovered dorsal root ganglia (DRGs) from 90 organ donors, 19 of whom had medical indices for diabetic painful neuropathy (DPN). Nageotte nodules, dead sensory neurons engulfed by non-neuronal cells, were abundant in DPN DRGs and accounted for 25% of all neurons. Peripherin-and Nav1.7-positive dystrophic axons invaded Nageotte nodules, forming small neuroma-like structures. Using histology and spatial sequencing, we demonstrate that Nageotte nodules are mainly composed of satellite glia and non-myelinating Schwann cells that express SPP1 and are intertwined with sprouting sensory axons originating from neighboring neurons. Our findings solve a 100-year mystery of the nature of Nageotte nodules linking these pathological structures to pain and sensory loss in DPN.

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bioRxiv2024

Ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans

Ephrin-B-EphB signaling promotes pain through signaling between dorsal root ganglion (DRG) neurons and spinal cord neurons in the dorsal horn, and through signaling between peripheral cells and EphB receptors expressed by DRG neurons. Previous findings link ephrin-B expression in painful peripheral tissues in patients to chronic pain, suggesting the clinical significance of this signaling, but the direct effects of ephrins on DRG neurons have not been widely studied. We hypothesized that ephrin-B2 would promote nociceptor plasticity and hyperalgesic priming through MNK-eIF4E signaling, a critical mechanism for nociceptive plasticity induced by growth factors, cytokines and nerve injury. Our work demonstrates that ephrin-B2-EphB2 signaling drives activation of MNK-eIF4E in DRG neurons to cause an enhanced response to inflammatory mediator signaling in both mice and humans and hyperalgesic priming in two models in mice. Both male and female mice developed dose-dependent mechanical hypersensitivity in response to ephrin-B2, and both sexes showed hyperalgesic priming when challenged with PGE2 injection into the same hindpaw. Acute nociceptive behaviors and hyperalgesic priming were blocked in mice lacking MNK1 (Mknk1 knockout mice) and by the MNK inhibitor eFT508. Similar effects on hyperalgesic priming were seen in a dural injection model. We generated a sensory neuron specific knockout of EphB2 using Pirt-Cre mice and found that these mice lacked responses to ephrin-B2 injection. We used Ca2+-imaging to determine direct effects of ephrin-B2 on DRG neurons and found that ephrin-B2 treatment enhanced Ca2+ transients in response to PGE2 which were absent in DRG neurons from MNK1-/- and EphB2-PirtCre mice. In experiments on human DRG neurons we found that ephrin-B2 increased eIF4E phosphorylation and enhanced Ca2+ responses to PGE2 treatment, both of which were blocked by eFT508 treatment. We conclude that ephrin-B2 acts directly on mouse and human sensory neurons to induce nociceptor plasticity via MNK-eIF4E signaling. The findings offer insight into how ephrin-B signaling promotes pain, and suggests treatment avenues for prevention or reversal of chronic pain associated with EphB activation in sensory neurons. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=153 HEIGHT=200 SRC="FIGDIR/small/581414v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@9ff5c9org.highwire.dtl.DTLVardef@1c17916org.highwire.dtl.DTLVardef@f4a5b0org.highwire.dtl.DTLVardef@1aa00c6_HPS_FORMAT_FIGEXP M_FIG C_FIG

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bioRxiv2023

Protease-Activated Receptor 2 (PAR2) expressed in sensory neurons contributes to signs of pain and neuropathy in paclitaxel treated mice

Background and PurposeChemotherapy-Induced Peripheral Neuropathy (CIPN) is a common, dose-limiting side effect of cancer therapy. Protease-activated receptor 2 (PAR2) is implicated in a variety of pathologies, including CIPN. In this study, we demonstrate the role of PAR2 expressed in sensory neurons in a paclitaxel (PTX)-induced model of CIPN in mice. Experimental ApproachCIPN was induced in both PAR2 knockout/WT mice and mice with PAR2 ablated in sensory neurons via the intraperitoneal injection of paclitaxel. In vivo behavioral studies were done in mice using von Frey filaments and the Mouse Grimace Scale. We then examined immunohistochemical staining of dorsal root ganglion (DRG) and hind paw skin samples from CIPN mice to measure satellite cell gliosis and intra-epidermal nerve fiber (IENF) density. Pharmacological reversal of CIPN pain was tested with the PAR2 antagonist C781 Key ResultsMechanical allodynia caused by paclitaxel treatment was alleviated in PAR2 knockout mice of both sexes. In the PAR2 sensory neuronal conditional knockout (cKO) mice, both mechanical allodynia and facial grimacing were attenuated in mice of both sexes. In the dorsal root ganglion of the paclitaxel-treated PAR2 cKO mice, satellite glial cell activation was reduced compared to control mice. IENF density analysis of the skin showed that the paclitaxel-treated control mice have a reduction in nerve fiber density while the PAR2 cKO mice had a comparable skin innervation as the vehicle-treated animals. Similar results were seen with satellite cell gliosis in the DRG where gliosis induced by PTX was absent in PAR cKO mice. Finally, C781 was able to transiently reverse established PTX-evoked mechanical allodynia. Conclusions and ImplicationsOur work demonstrates that PAR2 expressed in sensory neurons plays a key role in paclitaxel-induced mechanical allodynia, spontaneous pain and signs of neuropathy, suggesting PAR2 as a possible therapeutic target in multiple aspects of paclitaxel CIPN.

neuroscience↗

bioRxiv2023

NaV1.7 mRNA and protein expression in putative projection neurons of the human spinal dorsal horn

NaV1.7, a membrane-bound voltage-gated sodium channel, is preferentially expressed along primary sensory neurons, including their peripheral & central nerve endings, axons, and soma within the dorsal root ganglia and plays an integral role in amplifying membrane depolarization and pain neurotransmission. Loss- and gain-of-function mutations in the gene encoding NaV1.7, SCN9A, are associated with a complete loss of pain sensation or exacerbated pain in humans, respectively. As an enticing pain target supported by human genetic validation, many compounds have been developed to inhibit NaV1.7 but have disappointed in clinical trials. The underlying reasons are still unclear, but recent reports suggest that inhibiting NaV1.7 in central terminals of nociceptor afferents is critical for achieving pain relief by pharmacological inhibition of NaV1.7. We report for the first time that NaV1.7 mRNA is expressed in putative projection neurons (NK1R+) in the human spinal dorsal horn, predominantly in lamina 1 and 2, as well as in deep dorsal horn neurons and motor neurons in the ventral horn. NaV1.7 protein was found in the central axons of sensory neurons terminating in lamina 1-2, but also was detected in the axon initial segment of resident spinal dorsal horn neurons and in axons entering the anterior commissure. Given that projection neurons are critical for conveying nociceptive information from the dorsal horn to the brain, these data support that dorsal horn NaV1.7 expression may play an unappreciated role in pain phenotypes observed in humans with genetic SCN9A mutations, and in achieving analgesic efficacy in clinical trials.

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bioRxiv2022

Fragile X Mental Retardation Protein (FMRP) expression in human nociceptor axons of the spinal dorsal horn-- Implications for RNA targeting and localized translation

Fragile X Mental Retardation Protein (FMRP) regulates activity-dependent RNA localization and local translation to modulate synaptic plasticity throughout the CNS. Mutations in the FMR1 gene that hinder or ablate FMRP function cause Fragile X Syndrome (FXS), a disorder associated with sensory processing dysfunction. FXS pre-mutations are associated with increased FMRP expression and neurological impairments including sex dimorphic presentations of chronic pain. In mice, FMRP ablation causes dysregulated DRG neuron excitability and synaptic vesicle exocytosis, spinal circuit activity, and decreased translation-dependent nociceptive sensitization. Activity-dependent, local translation is a key mechanism for enhancing primary nociceptor excitability which promotes pain in animals and humans. These works indicate that FMRP likely regulates nociception and pain at the level of the primary nociceptor or spinal cord. Therefore, we sought to better understand FMRP expression in the human dorsal root ganglion (DRG) and spinal cord using immunostaining in organ donor tissues. We find that FMRP is highly expressed in DRG and spinal neuron subsets with substantia gelatinosa exhibiting the most abundant immunoreactivity in spinal synaptic fields. Here, it is expressed in nociceptor axons. FMRP puncta colocalized with Nav1.7 and TRPV1 receptor signals suggesting a pool of axoplasmic FMRP localizes to plasma membrane-associated loci in these branches. Interestingly, FMRP puncta exhibited notable colocalization with calcitonin gene-related peptide (CGRP) immunoreactivity selectively in female spinal cord. Our results support a regulatory role for FMRP in human nociceptor axons of the dorsal horn and implicate it in the sex dimorphic actions of CGRP signaling in nociceptive sensitization and chronic pain.

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bioRxiv2022

Resveratrol increases tear production and spontaneous ocular pain after corneal abrasion in male, but not female, rats using a preclinical model of photorefractive keratectomy (PRK)

Photorefractive keratectomy (PRK) is an alternative to LASIK and can cause intense acute pain that is often not relieved by standard treatments. To assess potential therapeutics for this type of acute pain, appropriate preclinical models are needed. Herein we describe a rodent preclinical model of PRK and a multi-faceted approach to determine the therapeutic potential of resveratrol, a natural phytoestrogen, on pain, tear production, and the corneal epithelium. Studies were conducted in male and female Sprague-Dawley rats. Heptanol was applied to one eye and the superficial corneal epithelium was removed, mimicking the abrasion seen in PRK. Spontaneous pain was assessed with orbital tightening (OT) scores for 7 days. Corneal abrasion increased OT scores in both male and female rats with peak responses at 24 - 48 hours. Topical application of resveratrol had a sex-specific effect on OT scores and tear production. Resveratrol increased OT scores in abraded males, but not females, at 72 hours and 1 week after abrasion. Resveratrol dose-dependently increased tear production in abraded males, but had no effect in abraded females. While there was no correlation between OT score at 1 week and tear production, CGRP content of corneal nerves was positively correlated with 1 week OT score. There was also a significant increase in CD68-labeled macrophages in resveratrol-treated abraded corneas as compared to naive corneas. These findings demonstrate the usefulness of our preclinical PRK model for the assessment of ocular pain therapeutics and indicate that topical resveratrol may not be useful for managing PRK-induced pain.

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bioRxiv2021

RNA Profiling of Neuropathic Pain-Associated Human DRGs Reveal Sex-differences in Neuro-immune Interactions Promoting Pain

Neuropathic pain is a leading cause of high impact pain, is often disabling and is poorly managed by current therapeutics. Here we focused on a unique group of neuropathic pain patients undergoing thoracic vertebrectomy where the DRG is removed as part of the surgery allowing for molecular characterization and identification of mechanistic drivers of neuropathic pain independently of preclinical models. Our goal was to quantify whole transcriptome RNA abundances using RNA-seq in pain-associated human DRGs from these patients, allowing comprehensive identification of molecular changes in these samples by contrasting them with non-pain associated DRGs. We sequenced 70 human DRGs, including over 50 having mRNA libraries with neuronal mRNA. Our expression analysis revealed profound sex differences in differentially expressed genes including increase of IL1B, TNF, CXCL14, and OSM in male and including CCL1, CCL21, PENK and TLR3 in female DRGs associated with neuropathic pain. Co-expression modules revealed enrichment in members of JUN-FOS signaling in males, and centromere protein coding genes in females. Neuro-immune signaling pathways revealed distinct cytokine signaling pathways associated with neuropathic pain in males (OSM, LIF, SOCS1) and females (CCL1, CCL19, CCL21). We validated cellular expression profiles of a subset of these findings using RNAscope in situ hybridization. Our findings give direct support for sex differences in underlying mechanisms of neuropathic pain in patient populations.

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