Neurobiology of Pain最新文献

{"title":"Neurobiology of migraine progression","authors":"Wanakorn Rattanawong ,&nbsp;Alan Rapoport ,&nbsp;Anan Srikiatkhachorn","doi":"10.1016/j.ynpai.2022.100094","DOIUrl":"10.1016/j.ynpai.2022.100094","url":null,"abstract":"<div><p>Chronic migraine is one of the most devastating headache disorders. The estimated prevalence is 1.4–2.2% in the population. The factors which may predispose to the process of migraine progression include high frequency of migraine attacks, medication overuse, comorbid pain syndromes, and obesity. Several studies showed that chronic migraine results in the substantial anatomical and physiological changes in the brain. Despite no clear explanation regarding the pathophysiologic process leading to the progression, certain features such as increased sensory sensitivity, cutaneous allodynia, impaired habituation, identify the neuronal hyperexcitability as the plausible mechanism. In this review, we describe two main mechanisms which can lead to this hyperexcitability. The first is persistent sensitization caused by repetitive and prolonged trigeminal nociceptive activation. This process results in changes in several brain networks related to both pain and non-pain behaviours. The second mechanism is the decrease in endogenous brainstem inhibitory control, hence increasing the excitability of neurons in the trigeminal noceptive system and cerebral cortex. The combination of increased pain matrix connectivity, including hypothalamic hyperactivity and a weak serotonergic system, may contribute to migraine chronification.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"12 ","pages":"Article 100094"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6b/e5/main.PMC9204797.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40026632","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":"Delta opioid receptors in Nav1.8 expressing peripheral neurons partially regulate the effect of delta agonist in models of migraine and opioid-induced hyperalgesia","authors":"Zachariah Bertels,&nbsp;Isaac J. Dripps,&nbsp;Pal Shah,&nbsp;Laura S. Moye,&nbsp;Alycia F. Tipton,&nbsp;Kendra Siegersma,&nbsp;Amynah A. Pradhan","doi":"10.1016/j.ynpai.2022.100099","DOIUrl":"10.1016/j.ynpai.2022.100099","url":null,"abstract":"<div><p>Migraine is one of the most common pain disorders and causes disability in millions of people every year. Delta opioid receptors (DOR) have been identified as a novel therapeutic target for migraine and other headache disorders. DORs are present in both peripheral and central regions and it is unclear which receptor populations regulate migraine-associated effects. The aim of this study was to determine if DOR expressed in peripheral nociceptors regulates headache associated endpoints and the effect of delta agonists within these mouse models. We used a conditional knockout, in which DOR was selectively deleted from Nav1.8 expressing cells. Nav1.8-DOR mice and loxP control littermates were tested in models of chronic migraine-associated allodynia, opioid-induced hyperalgesia, migraine-associated negative affect, and aura. Nav1.8-DOR and loxP mice had comparable effect sizes in all of these models. The anti-allodynic effect of the DOR agonist, SNC80, was slightly diminished in the nitroglycerin model of migraine. Intriguingly, in the OIH model the peripheral effects of SNC80 were completely lost in Nav1.8-DOR mice while the cephalic effects remained intact. Regardless of genotype, SNC80 continued to inhibit conditioned place aversion associated with nitroglycerin and decreased cortical spreading depression events associated with migraine aura. These results suggest that DOR in Nav1.8-expressing nociceptors do not critically regulate the anti-migraine effects of delta agonist; and that brain-penetrant delta agonists would be a more effective drug development strategy.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"12 ","pages":"Article 100099"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/22/main.PMC9289726.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40524429","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":"Low-dose interleukin-2 reverses chronic migraine-related sensitizations through peripheral interleukin-10 and transforming growth factor beta-1 signaling","authors":"Zhaohua Guo ,&nbsp;Jintao Zhang ,&nbsp;Xuemei Liu ,&nbsp;Jacqueline Unsinger ,&nbsp;Richard S Hotchkiss ,&nbsp;Yu-Qing Cao","doi":"10.1016/j.ynpai.2022.100096","DOIUrl":"10.1016/j.ynpai.2022.100096","url":null,"abstract":"<div><p>Low-dose interleukin-2 (LD-IL-2) treatment has been shown to effectively reverse chronic migraine-related behaviors and the sensitization of trigeminal ganglion (TG) neurons through expansion and activation of peripheral regulatory T cells (Tregs) in mice. In this study, we investigated the molecular mechanisms underlying the effects of LD-IL-2 and Treg cells. LD-IL-2 treatment increases the production of cytokines interleukin-10 (IL-10) and transforming growth factor beta-1 (TGFβ1) in T cells, especially Treg cells, suggesting that they may mediate the therapeutic effect of LD-IL-2. Indeed, neutralizing antibodies against either IL-10 or TGFβ completely blocked the effects of LD-IL-2 on the facial mechanical hypersensitivity as well as the sensitization of TG neurons resulting from repeated nitroglycerin (NTG, a reliable trigger of migraine in patients) administration in mice, indicating that LD-IL-2 and Treg cells engage both peripheral IL-10 and TGFβ signaling pathways to reverse chronic-migraine related sensitizations. In an <em>in vitro</em> assay, incubation of TG culture with exogenous IL-10 or TGFβ1 fully reversed NTG-induced sensitization of TG neurons, suggesting that the IL-10 and TGFβ1 signaling in TG neurons contribute to LD-IL-2′s therapeutic effects. Collectively, these results not only elucidate the molecular mechanisms through which LD-IL-2 and Treg cells reverse chronic-migraine related sensitizations, but also suggest that the IL-10 and TGFβ1 signaling pathways in TG neurons are potential targets for chronic migraine therapy.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"12 ","pages":"Article 100096"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6e/42/main.PMC9207571.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40224133","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":"Interplay between exosomes and autophagy machinery in pain management: State of the art","authors":"Hamidreza Morteza Bagi ,&nbsp;Sajjad Ahmadi ,&nbsp;Faezeh Tarighat ,&nbsp;Reza Rahbarghazi ,&nbsp;Hassan Soleimanpour","doi":"10.1016/j.ynpai.2022.100095","DOIUrl":"10.1016/j.ynpai.2022.100095","url":null,"abstract":"<div><p>Despite recent progress regarding inexpensive medical approaches, many individuals suffer from moderate to severe pain globally. The discovery and advent of exosomes, as biological nano-sized vesicles, has revolutionized current knowledge about underlying mechanisms associated with several pathological conditions. Indeed, these particles are touted as biological bio-shuttles with the potential to carry specific signaling biomolecules to cells in proximity and remote sites, maintaining cell-to-cell communication in a paracrine manner. A piece of evidence points to an intricate relationship between exosome biogenesis and autophagy signaling pathways at different molecular levels. A close collaboration of autophagic response with exosome release can affect the body’s hemostasis and physiology of different cell types. This review is a preliminary attempt to highlight the possible interface of autophagy flux and exosome biogenesis on pain management with a special focus on neuropathic pain. It is thought that this review article will help us to understand the interplay of autophagic response and exosome biogenesis in the management of pain under pathological conditions. The application of therapies targeting autophagy pathway and exosome abscission can be an alternative strategy in the regulation of pain.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"12 ","pages":"Article 100095"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2a/ec/main.PMC9198378.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9179671","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":"Stimulation of CGRP-expressing neurons in the medial cerebellar nucleus induces light and touch sensitivity in mice","authors":"Mengya Wang ,&nbsp;William C. Castonguay ,&nbsp;Thomas L. Duong ,&nbsp;Michael W. Huebner ,&nbsp;Harold C. Flinn ,&nbsp;Agatha M. Greenway ,&nbsp;Andrew F. Russo ,&nbsp;Levi P. Sowers","doi":"10.1016/j.ynpai.2022.100098","DOIUrl":"10.1016/j.ynpai.2022.100098","url":null,"abstract":"<div><p>Calcitonin gene-related peptide (CGRP) is considered a major player in migraine pathophysiology. However, the location and mechanisms of CGRP actions in migraine are not clearly elucidated. One important question yet to be answered is: Does central CGRP signaling play a role in migraine? One candidate site is the cerebellum, which serves as a sensory and motor integration center and is activated in migraine patients. The cerebellum has the most CGRP binding sites in the central nervous system and a deep cerebellar nucleus, the medial nucleus (MN), expresses CGRP (MN^CGRP). A previous study demonstrated that CGRP delivery into the cerebellum induced migraine-like behaviors. We hypothesized that stimulation of MN^CGRP neurons might induce migraine-like behaviors. To test the hypothesis, we used an optogenetic strategy using <em>Calca^Cre/+</em> mice to drive Cre-dependent expression of channelrhodopsin-2 selectively in CGRP neurons in the cerebellar MN. A battery of behavioral tests was done to assess preclinical behaviors that are surrogates of migraine symptoms, including light aversion, cutaneous allodynia, and spontaneous pain when MN^CGRP neurons were optically stimulated. Motor functions were also assessed. Optical stimulation of MN^CGRP neurons decreased the time spent in the light, which was coupled to increased time spent resting in the dark, but not the light. These changes were only significant in female mice. Plantar tactile sensitivity was increased in the ipsilateral paws of both sexes, but contralateral paw data were less clear. There was no significant increase in anxiety-like behavior, spontaneous pain (squint), or changes in gait. These discoveries reveal that MN^CGRP neurons may contribute to migraine-like sensory hypersensitivity to light and touch.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"12 ","pages":"Article 100098"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40579648","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":"Comprehensive phenotyping of cutaneous afferents reveals early-onset alterations in nociceptor response properties, release of CGRP, and hindpaw edema following spinal cord injury","authors":"Olivia C. Eller ,&nbsp;Rena N. Stair ,&nbsp;Christopher Neal ,&nbsp;Peter S.N. Rowe ,&nbsp;Jennifer Nelson-Brantley ,&nbsp;Erin E. Young ,&nbsp;Kyle M. Baumbauer","doi":"10.1016/j.ynpai.2022.100097","DOIUrl":"10.1016/j.ynpai.2022.100097","url":null,"abstract":"<div><p>Spinal cord injury (SCI) is a complex syndrome that has profound effects on patient well-being, including the development of medically-resistant chronic pain. The mechanisms underlying SCI pain have been the subject of thorough investigation but remain poorly understood. While the majority of the research has focused on changes occurring within and surrounding the site of injury in the spinal cord, there is now a consensus that alterations within the peripheral nervous system, namely sensitization of nociceptors, contribute to the development and maintenance of chronic SCI pain. Using an <em>ex vivo</em> skin/nerve/DRG/spinal cord preparation to characterize afferent response properties following SCI, we found that SCI increased mechanical and thermal responding, as well as the incidence of spontaneous activity (SA) and afterdischarge (AD), in below-level C-fiber nociceptors 24 hr following injury relative to naïve controls. Interestingly, the distribution of nociceptors that exhibit SA and AD are not identical, and the development of SA was observed more frequently in nociceptors with low heat thresholds, while AD was found more frequently in nociceptors with high heat thresholds. We also found that SCI resulted in hindpaw edema and elevated cutaneous calcitonin gene-related peptide (CGRP) concentration that were not observed in naïve mice. These results suggest that SCI causes a rapidly developing nociceptor sensitization and peripheral inflammation that may contribute to the early emergence and persistence of chronic SCI pain.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"12 ","pages":"Article 100097"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/6a/main.PMC9218836.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40399650","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":"Cell specific regulation of NaV1.7 activity and trafficking in rat nodose ganglia neurons","authors":"Santiago I. Loya-López ,&nbsp;Paz Duran ,&nbsp;Dongzhi Ran ,&nbsp;Aida Calderon-Rivera ,&nbsp;Kimberly Gomez ,&nbsp;Aubin Moutal ,&nbsp;Rajesh Khanna","doi":"10.1016/j.ynpai.2022.100109","DOIUrl":"10.1016/j.ynpai.2022.100109","url":null,"abstract":"<div><p>The voltage-gated sodium NaV1.7 channel sets the threshold for electrogenesis. Mutations in the gene encoding human NaV1.7 (<em>SCN9A</em>) cause painful neuropathies or pain insensitivity. In dorsal root ganglion (DRG) neurons, activity and trafficking of NaV1.7 are regulated by the auxiliary collapsin response mediator protein 2 (CRMP2). Specifically, preventing addition of a small ubiquitin-like modifier (SUMO), by the E2 SUMO-conjugating enzyme Ubc9, at lysine-374 (K374) of CRMP2 reduces NaV1.7 channel trafficking and activity. We previously identified a small molecule, designated <strong>194</strong>, that prevented CRMP2 SUMOylation by Ubc9 to reduce NaV1.7 surface expression and currents, leading to a reduction in spinal nociceptive transmission, and culminating in normalization of mechanical allodynia in models of neuropathic pain. In this study, we investigated whether NaV1.7 control via CRMP2-SUMOylation is conserved in nodose ganglion (NG) neurons. This study was motivated by our desire to develop <strong>194</strong> as a safe, non-opioid substitute for persistent pain, which led us to wonder how <strong>194</strong> would impact NaV1.7 in NG neurons, which are responsible for driving the cough reflex. We found functioning NaV1.7 channels in NG neurons; however, they were resistant to downregulation via either CRMP2 knockdown or pharmacological inhibition of CRMP2 SUMOylation by <strong>194.</strong> CRMP2 SUMOylation and interaction with NaV1.7 was consered in NG neurons but the endocytic machinery was deficient in the endocytic adaptor protein Numb. Overexpression of Numb rescued CRMP2-dependent regulation on NaV1.7, rendering NG neurons sensitive to <strong>194.</strong> Altogether, these data point at the existence of cell-specific mechanisms regulating NaV1.7 trafficking.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"12 ","pages":"Article 100109"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/09/f1/main.PMC9755031.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10404950","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":"Investigation on how dynamic effective connectivity patterns encode the fluctuating pain intensity in chronic migraine","authors":"Iege Bassez ,&nbsp;Frederik Van de Steen ,&nbsp;Sophie Hackl ,&nbsp;Pauline Jahn ,&nbsp;Astrid Mayr ,&nbsp;Daniele Marinazzo ,&nbsp;Enrico Schulz","doi":"10.1016/j.ynpai.2022.100100","DOIUrl":"10.1016/j.ynpai.2022.100100","url":null,"abstract":"<div><p>Chronic migraine is characterised by persistent headaches for &gt;15 days per month; the intensity of the pain is fluctuating over time. Here, we explored the dynamic interplay of connectivity patterns between regions known to be related to pain processing and their relation to the ongoing dynamic pain experience. We recorded EEG from 80 sessions (20 chronic migraine patients in 4 separate sessions of 25 min). The patients were asked to continuously rate the intensity of their endogenous headache. On different time-windows, a dynamic causal model (DCM) of cross spectral responses was inverted to estimate connectivity strengths. For each patient and session, the evolving dynamics of effective connectivity were related to pain intensities and to pain intensity changes by using a Bayesian linear model. Hierarchical Bayesian modelling was further used to examine which connectivity-pain relations are consistent across sessions and across patients.</p><p>The results reflect the multi-facetted clinical picture of the disease. Across all sessions, each patient with chronic migraine exhibited a distinct pattern of pain intensity-related cortical connectivity. The diversity of the individual findings are accompanied by inconsistent relations between the connectivity parameters and pain intensity or pain intensity changes at group level. This suggests a rejection of the idea of a common neuronal core problem for chronic migraine.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"12 ","pages":"Article 100100"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6b/d8/main.PMC9424568.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40343105","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":"Investigation on how dynamic effective connectivity patterns encode the fluctuating pain intensity in chronic migraine","authors":"I. Bassez, Frederik Van de Steen, Sophie Hackl, Pauline Jahn, A. Mayr, D. Marinazzo, E. Schulz","doi":"10.1101/2022.02.23.481583","DOIUrl":"https://doi.org/10.1101/2022.02.23.481583","url":null,"abstract":"Chronic migraine is characterised by persistent headaches for more than 15 days per month; the intensity of the pain is fluctuating over time. Here, we explored the dynamic interplay of connectivity patterns between regions known to be related to pain processing and their relation to the ongoing dynamic pain experience. We recorded EEG from 80 sessions (20 chronic migraine patients in 4 separate sessions of 25 minutes). The patients were asked to continuously rate the intensity of their endogenous headache. On different time-windows, a dynamic causal model (DCM) of cross spectral responses was inverted to estimate connectivity strengths. For each patient and session, the evolving dynamics of effective connectivity were related to pain intensities and to pain intensity changes by using a Bayesian linear model. Hierarchical Bayesian modelling was further used to examine which connectivity-pain relations are consistent across sessions and across patients. The results reflect the multi-facetted clinical picture of the disease. Across all sessions, each patient with chronic migraine exhibited a distinct pattern of pain intensity-related cortical connectivity. The diversity of the individual findings are accompanied by inconsistent relations between the connectivity parameters and pain intensity or pain intensity changes at group level. This suggests a rejection of the idea of a common neuronal core problem for chronic migraine.","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44198126","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":"Cortical spreading depression and meningeal nociception","authors":"Simone Carneiro-Nascimento,&nbsp;Dan Levy","doi":"10.1016/j.ynpai.2022.100091","DOIUrl":"10.1016/j.ynpai.2022.100091","url":null,"abstract":"<div><p>Migraine results in an enormous burden on individuals and societies due to its high prevalence, significant disability, and considerable economic costs. Current treatment options for migraine remain inadequate, and the development of novel therapies is severely hindered by the incomplete understanding of the mechanisms responsible for the pain. The sensory innervation of the cranial meninges is now considered a key player in migraine headache genesis. Recent studies have significantly advanced our understanding of some of the processes that drive meningeal nociceptive neurons, which may be targeted therapeutically to abort or prevent migraine pain. In this review we will summarize our current understanding of the mechanisms that contribute to the genesis of the headache in one migraine subtype – migraine with aura. We will focus on animal studies that address the notion that cortical spreading depression is a critical process that drives meningeal nociception in migraine with aura, and discuss recent insights into some of the proposed underlying mechanisms.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"11 ","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452073X22000083/pdfft?md5=40c3bcd08027c20c065bd225488cd5a8&pid=1-s2.0-S2452073X22000083-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41389722","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}