Neurobiology of Pain最新文献

{"title":"Metformin protects from oxaliplatin induced peripheral neuropathy in rats","authors":"N.W. Martinez ,&nbsp;A. Sánchez ,&nbsp;P. Diaz ,&nbsp;R. Broekhuizen ,&nbsp;J. Godoy ,&nbsp;S. Mondaca ,&nbsp;A. Catenaccio ,&nbsp;P. Macanas ,&nbsp;B. Nervi ,&nbsp;M. Calvo ,&nbsp;F.A. Court","doi":"10.1016/j.ynpai.2020.100048","DOIUrl":"10.1016/j.ynpai.2020.100048","url":null,"abstract":"<div><p>Oxaliplatin is a commonly used drug to treat cancer, extending the rate of disease-free survival by 20% in colorectal cancer. However, oxaliplatin induces a disabling form of neuropathy resulting in more than 60% of patients having to reduce or discontinue oxaliplatin, negatively impacting their chance of survival. Oxaliplatin-induced neuropathies are accompanied by degeneration of sensory fibers in the epidermis and hyperexcitability of sensory neurons. These morphological and functional changes have been associated with sensory symptoms such as dysesthesia, paresthesia and mechanical and cold allodynia. Various strategies have been proposed to prevent or treat oxaliplatin-induced neuropathies without success. The anti-diabetic drug metformin has been recently shown to exert neuroprotection in other chemotherapy-induced neuropathies, so here we aimed to test if metformin can prevent the development of oxaliplatin-induced neuropathy in a rat model of this condition. Animals treated with oxaliplatin developed significant intraepidermal fiber degeneration, a mild gliosis in the spinal cord, and mechanical and cold hyperalgesia. The concomitant use of metformin prevented degeneration of intraepidermal fibers, gliosis, and the altered sensitivity. Our evidence further supports metformin as a new approach to prevent oxaliplatin-induced neuropathy with a potential important clinical impact.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"8 ","pages":"Article 100048"},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ynpai.2020.100048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38002747","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":"Chronic inflammatory pain alters alcohol-regulated frontocortical signaling and associations between alcohol drinking and thermal sensitivity","authors":"M. Adrienne McGinn ,&nbsp;Kimberly N. Edwards ,&nbsp;Scott Edwards","doi":"10.1016/j.ynpai.2020.100052","DOIUrl":"10.1016/j.ynpai.2020.100052","url":null,"abstract":"<div><p>Alcohol use disorder (AUD) is a chronic, relapsing psychiatric disorder that is characterized by the emergence of negative affective states. The transition from recreational, limited intake to uncontrolled, escalated intake is proposed to involve a transition from positive to negative reinforcement mechanisms for seeking alcohol. Past work has identified the emergence of significant hyperalgesia/allodynia in alcohol-dependent animals, which may serve as a key negative reinforcement mechanism. Chronic pain has been associated with enhanced extracellular signal-regulated kinase (ERK) activity in cortical and subcortical nociceptive areas. Additionally, both pain and AUD have been associated with increased activity of the glucocorticoid receptor (GR), a key mediator of stress responsiveness. The objectives of the current study were to first determine relationships between thermal nociceptive sensitivity and alcohol drinking in male Wistar rats. While inflammatory pain induced by complete Freund’s adjuvant (CFA) administration did not modify escalation of home cage drinking in animals over four weeks, the relationship between drinking levels and hyperalgesia symptoms reversed between acute (1 week) and chronic (3–4 week) periods post-CFA administration, suggesting that either the motivational or analgesic effects of alcohol may be altered over the time course of chronic pain. We next examined ERK and GR phosphorylation in pain-related brain areas (including the central amygdala and prefrontal cortex subregions) in animals experiencing acute withdrawal from binge alcohol administration (2 g/kg, 6 h withdrawal) and CFA administration (four weeks) to model the neurobiological consequences of binge alcohol exposure in the context of pain. We observed a significant interaction between alcohol and pain state, whereby alcohol withdrawal increased ERK phosphorylation across all four frontocortical areas examined, although this effect was absent in animals experiencing chronic inflammatory pain. Alcohol withdrawal also increased GR phosphorylation across all four frontocortical areas, but these changes were not altered by CFA. Interestingly, we observed significant inter-brain regional correlations in GR phosphorylation between the insula and other regions investigated only in animals exposed to both alcohol and CFA, suggesting coordinated activity in insula circuitry and glucocorticoid signaling in this context. The results of these studies provide a greater understanding of the neurobiology of AUD and will contribute to the development of effective treatment strategies for comorbid AUD and pain.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"8 ","pages":"Article 100052"},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ynpai.2020.100052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38446145","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":"Human sensory neurons derived from pluripotent stem cells for disease modelling and personalized medicine","authors":"Angelika Lampert ,&nbsp;David L. Bennett ,&nbsp;Lucy A. McDermott ,&nbsp;Anika Neureiter ,&nbsp;Esther Eberhardt ,&nbsp;Beate Winner ,&nbsp;Martin Zenke","doi":"10.1016/j.ynpai.2020.100055","DOIUrl":"10.1016/j.ynpai.2020.100055","url":null,"abstract":"<div><p>In this concise Mini-Review we will summarize ongoing developments of new techniques to study physiology and pathophysiology of the peripheral sensory nervous system in human stem cell derived models. We will focus on recent developments of reprogramming somatic cells into induced pluripotent stem cells, neural differentiation towards neuronal progenitors and human sensory neurons.</p><p>We will sum up the high potential of this new technique for disease modelling of human neuropathies with a focus on genetic pain syndromes, such as gain- and loss-of-function mutations in voltage-gated sodium channels. The stem cell derived human sensory neurons are used for drug testing and we will summarize their usefulness for individualized treatment identification in patients with neuropathic pain. The review will give an outlook on potential application of this technique as companion diagnostics and for personalized medicine.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"8 ","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ynpai.2020.100055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38751963","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":"Peripheral mechanisms of arthritic pain: A proposal to leverage large animals for in vitro studies","authors":"Sampurna Chakrabarti ,&nbsp;Minji Ai ,&nbsp;Frances M.D. Henson ,&nbsp;Ewan St. John Smith","doi":"10.1016/j.ynpai.2020.100051","DOIUrl":"https://doi.org/10.1016/j.ynpai.2020.100051","url":null,"abstract":"<div><p>Pain arising from musculoskeletal disorders such as arthritis is one of the leading causes of disability. Whereas the past 20-years has seen an increase in targeted therapies for rheumatoid arthritis (RA), other arthritis conditions, especially osteoarthritis, remain poorly treated. Although modulation of central pain pathways occurs in chronic arthritis, multiple lines of evidence indicate that peripherally driven pain is important in arthritic pain. To understand the peripheral mechanisms of arthritic pain, various <em>in vitro</em> and <em>in vivo</em> models have been developed, largely in rodents. Although rodent models provide numerous advantages for studying arthritis pathogenesis and treatment, the anatomy and biomechanics of rodent joints differ considerably to those of humans. By contrast, the anatomy and biomechanics of joints in larger animals, such as dogs, show greater similarity to human joints and thus studying them can provide novel insight for arthritis research. The purpose of this article is firstly to review models of arthritis and behavioral outcomes commonly used in large animals. Secondly, we review the existing <em>in vitro</em> models and assays used to study arthritic pain, primarily in rodents, and discuss the potential for adopting these strategies, as well as likely limitations, in large animals. We believe that exploring peripheral mechanisms of arthritic pain <em>in vitro</em> in large animals has the potential to reduce the veterinary burden of arthritis in commonly afflicted species like dogs, as well as to improve translatability of pain research into the clinic.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"8 ","pages":"Article 100051"},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ynpai.2020.100051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72103146","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":"A role for the microbiota in complex regional pain syndrome?","authors":"Lara W. Crock ,&nbsp;Megan T. Baldridge","doi":"10.1016/j.ynpai.2020.100054","DOIUrl":"10.1016/j.ynpai.2020.100054","url":null,"abstract":"<div><p>Complex regional pain syndrome (CRPS) is a debilitating neuroinflammatory condition of unknown etiology. Symptoms include excruciating pain and trophic changes in the limbs as defined by the Budapest criteria. The severity and functional recovery of CRPS, unlike most pain conditions, is quantifiable using a variation of the Budapest criteria known as the CRPS severity score. Like many chronic pain conditions, CRPS is difficult to treat once pain has been present for more than 12 months. However, previous work has demonstrated that a subset of patients with new-onset CRPS (~50%) improve if treated within one year, while the rest have minimal to no symptom improvement. Unfortunately, this leads to permanent disability and often requires invasive and costly treatments such as spinal cord stimulation or long-term opioid therapy. Because the etiology is unknown, treatment is multimodal, and often supportive. Biomarkers that predict severity or resolution of symptoms would significantly change treatment but have not yet been identified. Interestingly, there are case reports of remission or resolution of CRPS symptoms with the use of antibiotics known to affect the gut flora. Mouse studies have demonstrated that modulation of the gut microbiome is anti-nociceptive in visceral, inflammatory and neuropathic pain models. We hypothesize that the variable clinical potential for recovery and response to therapy in CRPS may be secondary to or reflected in changes in the gut microbiota. We suggest that the microbiota may mediate or reflect clinical status via the metabolome, activation of the immune system and/or microglial activation. We hypothesize that the gut microbiome is a potential mediator in development and persistence of CRPS symptoms and propose that the clinical condition of CRPS could provide a unique opportunity to identify biomarkers of the microbiota and potential therapies to prevent pain chronification.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"8 ","pages":"Article 100054"},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ynpai.2020.100054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38361463","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":"Sex differences in the role of atypical PKC within the basolateral nucleus of the amygdala in a mouse hyperalgesic priming model","authors":"Daniela Baptista-de-Souza ,&nbsp;Diana Tavares-Ferreira ,&nbsp;Salim Megat ,&nbsp;Ishwarya Sankaranarayanan ,&nbsp;Stephanie Shiers ,&nbsp;Christopher M. Flores ,&nbsp;Sourav Ghosh ,&nbsp;Ricardo Luiz Nunes-de-Souza ,&nbsp;Azair Canto-de-Souza ,&nbsp;Theodore J. Price","doi":"10.1016/j.ynpai.2020.100049","DOIUrl":"10.1016/j.ynpai.2020.100049","url":null,"abstract":"<div><p>Though sex differences in chronic pain have been consistently described in the literature, their underlying neural mechanisms are poorly understood. Previous work in humans has demonstrated that men and women differentially invoke distinct brain regions and circuits in coping with subjective pain unpleasantness. The goal of the present work was to elucidate the molecular mechanisms in the basolateral nucleus of the amygdala (BLA) that modulate hyperalgesic priming, a pain plasticity model, in males and females. We used plantar incision as the first, priming stimulus and prostaglandin E₂ (PGE₂) as the second stimulus. We sought to assess whether hyperalgesic priming can be prevented or reversed by pharmacologically manipulating molecular targets in the BLA of male or female mice. We found that administering ZIP, a cell-permeable inhibitor of aPKC, into the BLA attenuated aspects of hyperalgesic priming induced by plantar incision in males and females. However, incision only upregulated PKCζ/PKMζ immunoreactivity in the BLA of male mice, and deficits in hyperalgesic priming were seen only when we restricted our analysis to male <em>Prkcz^−/−</em> mice. On the other hand, intra-BLA microinjections of pep2m, a peptide that interferes with the trafficking and function of GluA2-containing AMPA receptors, a downstream target of aPKC, reduced mechanical hypersensitivity after plantar incision and disrupted the development of hyperalgesic priming in both male and female mice. In addition, pep2m treatment reduced facial grimacing and restored aberrant behavioral responses in the sucrose splash test in male and female primed mice. Immunofluorescence results demonstrated upregulation of GluA2 expression in the BLA of male and female primed mice, consistent with pep2m findings. We conclude that, in a model of incision-induced hyperalgesic priming, PKCζ/PKMζ in the BLA is critical for the development of hyperalgesic priming in males, while GluA2 in the BLA is crucial for the expression of both reflexive and affective pain-related behaviors in both male and female mice in this model. Our findings add to a growing body of evidence of sex differences in molecular pain mechanisms in the brain.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"8 ","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ynpai.2020.100049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38053014","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":"High trait impulsivity potentiates the effects of chronic pain on impulsive behavior","authors":"Ana Margarida Cunha ,&nbsp;Madalena Esteves ,&nbsp;Joana Pereira-Mendes ,&nbsp;Marco Rafael Guimarães ,&nbsp;Armando Almeida ,&nbsp;Hugo Leite-Almeida","doi":"10.1016/j.ynpai.2019.100042","DOIUrl":"10.1016/j.ynpai.2019.100042","url":null,"abstract":"<div><p>Preclinical studies on impulsive decision-making in chronic pain conditions are sparse and often contradictory. Outbred rat populations are heterogeneous regarding trait impulsivity manifestations and therefore we hypothesized that chronic pain-related alterations depend on individual traits. To test this hypothesis, we used male Wistar-Han rats in two independent experiments. Firstly, we tested the impact of spared nerve injury (SNI) in impulsive behavior evaluated by the variable delay-to-signal test (VDS). In the second experiment, SNI impact on impulsivity was again tested, but in groups previously categorized as high (HI) and low (LI) trait impulsivity in the VDS.</p><p>Results showed that in an heterogenous population SNI-related impact on motor impulsivity and delay intolerance cannot be detected. However, when baseline impulsivity was considered, HI showed a significantly higher delay intolerance than the respective controls more prevalent in left-lesioned animals and appearing to result from a response correction on prematurity from VDS I to VDS II, which was present in Sham and right-lesioned animals.</p><p>In conclusion, baseline differences should be more often considered when analyzing chronic pain impact. While this study pertained to impulsive behavior, other reports indicate that this can be generalized to other behavioral dimensions and that trait differences can influence not only the manifestation of comorbid behaviors but also pain itself in a complex and not totally understood manner.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"7 ","pages":"Article 100042"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ynpai.2019.100042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37503472","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":"Molecular mechanisms of cold pain","authors":"Donald Iain MacDonald ,&nbsp;John N. Wood,&nbsp;Edward C. Emery","doi":"10.1016/j.ynpai.2020.100044","DOIUrl":"10.1016/j.ynpai.2020.100044","url":null,"abstract":"<div><p>The sensation of cooling is essential for survival. Extreme cold is a noxious stimulus that drives protective behaviour and that we thus perceive as pain. However, chronic pain patients suffering from cold allodynia paradoxically experience innocuous cooling as excruciating pain. Peripheral sensory neurons that detect decreasing temperature express numerous cold-sensitive and voltage-gated ion channels that govern their response to cooling in health and disease. In this review, we discuss how these ion channels control the sense of cooling and cold pain under physiological conditions, before focusing on the molecular mechanisms by which ion channels can trigger pathological cold pain. With the ever-rising number of patients burdened by chronic pain, we end by highlighting the pressing need to define the cells and molecules involved in cold allodynia and so identify new, rational drug targets for the analgesic treatment of cold pain.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"7 ","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ynpai.2020.100044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37669555","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":"CD3+ T cells are critical for the resolution of comorbid inflammatory pain and depression-like behavior","authors":"Geoffroy Laumet,&nbsp;Jules D. Edralin,&nbsp;Robert Dantzer,&nbsp;Cobi J. Heijnen,&nbsp;Annemieke Kavelaars","doi":"10.1016/j.ynpai.2020.100043","DOIUrl":"https://doi.org/10.1016/j.ynpai.2020.100043","url":null,"abstract":"<div><h3>Background</h3><p>Chronic pain and depression often co-occur. The mechanisms underlying this comorbidity are incompletely understood. Here, we investigated the role of CD3⁺ T cells in an inflammatory model of comorbid persistent mechanical allodynia, spontaneous pain, and depression-like behavior in mice.</p></div><div><h3>Methods</h3><p>C57Bl/6 wt and <em>Rag2</em>^−/− mice were compared in their response to intraplantar administration of complete Freund’s adjuvant (CFA). Mechanical allodynia, spontaneous pain and depression-like behavior were assessed by von Frey, conditioned place preference and forced swim test respectively.</p></div><div><h3>Results</h3><p>Resolution of mechanical allodynia, spontaneous pain, and depression-like behavior was markedly delayed in <em>Rag2</em>^−/− mice that are devoid of adaptive immune cells. Reconstitution of <em>Rag2</em>^−/− mice with CD3⁺ T cells from WT mice before CFA injection normalized the resolution of indicators of pain and depression-like behavior. T cells did not contribute to onset or severity of indicators of pain and depression-like behavior. The lack of T cells did not affect cytokine expression in the paw, spinal cord and brain, indicating that the delayed resolution was not resulting from prolonged (neuro)inflammation.</p></div><div><h3>Conclusions</h3><p>Our findings show that T cells are critical for the natural resolution of mechanical allodynia, spontaneous pain, and depression-like behavior after an inflammatory challenge. Dysregulation of this T cell-mediated resolution pathway could contribute to the comorbidity of chronic pain and depression.</p></div><div><h3>Significance</h3><p>Chronic pain and depression are frequently associated with signs of inflammation. However, general immunosuppression is not sufficient to resolve comorbid pain and depression. Here we demonstrate that T cells are required for resolution of comorbid persistent mechanical allodynia, spontaneous pain, and depression in a model of peripheral inflammation, indicating the immune system can contribute to both onset and resolution of these comorbidities. Enhancing pro-resolution effects of T cells may have a major impact to treat patients with comorbid persistent pain and depression.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"7 ","pages":"Article 100043"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ynpai.2020.100043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72082947","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":"Microbes, microglia, and pain","authors":"Zoë Dworsky-Fried ,&nbsp;Bradley J. Kerr ,&nbsp;Anna M.W. Taylor","doi":"10.1016/j.ynpai.2020.100045","DOIUrl":"10.1016/j.ynpai.2020.100045","url":null,"abstract":"<div><p>Globally, it is estimated that one in five people suffer from chronic pain, with prevalence increasing with age. The pathophysiology of chronic pain encompasses complex sensory, immune, and inflammatory interactions within both the central and peripheral nervous systems. Microglia, the resident macrophages of the central nervous system (CNS), are critically involved in the initiation and persistence of chronic pain. Microglia respond to local signals from the CNS but are also modulated by signals from the gastrointestinal tract. Emerging data from preclinical and clinical studies suggest that communication between the gut microbiome, the community of bacteria residing within the gut, and microglia is involved in producing chronic pain. Targeted strategies that manipulate or restore the gut microbiome have been shown to reduce microglial activation and alleviate symptoms associated with inflammation. These data indicate that manipulations of the gut microbiome in chronic pain patients might be a viable strategy in improving pain outcomes. Herein, we discuss the evidence for a connection between microglia and the gut microbiome and explore the mechanisms by which commensal bacteria might influence microglial reactivity to drive chronic pain.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"7 ","pages":"Article 100045"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ynpai.2020.100045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37656308","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}