Molecular Pain最新文献

{"title":"Dehydrocorydaline alleviates sleep deprivation-induced persistent postoperative pain in adolescent mice through inhibiting microglial P2Y₁₂ receptor expression in the spinal cord.","authors":"Haikou Yang, Yufeng Zhang, Qingling Duan, Kun Ni, Yang Jiao, Jixiang Zhu, Jian Sun, Wei Zhang, Zhengliang Ma","doi":"10.1177/17448069231216234","DOIUrl":"10.1177/17448069231216234","url":null,"abstract":"<p><p>During adolescence, a second period of central nervous system (CNS) plasticity that follows the fetal period, which involves sleep deprivation (SD), becomes apparent. SD during adolescence may result in abnormal development of neural circuits, causing imbalance in neuronal excitation and inhibition, which not only results in pain, but increases the chances of developing emotion disorders in adulthood, such as anxiety and depression. The quantity of surgeries during adolescence is also consistently on the rise, yet the impact and underlying mechanism of preoperative SD on postoperative pain remain unexplored. This study demonstrates that preoperative SD induces upregulation of the P2Y₁₂ receptor, which is exclusively expressed on spinal microglia, and phosphorylation of its downstream signaling pathway p38Mitogen-activated protein/Nuclear transcription factor-κB (p38MAPK/NF-κB)in spinal microglia, thereby promoting microglia activation and microglial transformation into the proinflammatory M1 phenotype, resulting in increased expression of proinflammatory cytokines that exacerbate persisting postoperative incisional pain in adolescent mice. Both intrathecal minocycline (a microglia activation inhibitor) and MRS2395 (a P2Y₁₂ receptor blocker) effectively suppressed microglial activation and proinflammatory cytokine expression. Interestingly, supplementation with dehydrocorydaline (DHC), an extract of <i>Rhizoma Corydalis</i>, inhibited the P2Y₁₂/p38MAPK/NF-κB signaling pathway, microglia activation, and expression of pro-inflammatory cytokines in the model mice. Taken together, the results indicate that the P2Y₁₂ receptor and microglial activation are important factors in persistent postoperative pain caused by preoperative SD in adolescent mice and that DHC has analgesic effects by acting on these targets.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71522060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal alterations of pituitary adenylate cyclase activating polypeptide and its receptors in a rat model induced by recurrent chemical stimulations: Relevant to chronic migraine.","authors":"Hangfei Wu,&nbsp;Zhao Dong,&nbsp;Yinglu Liu,&nbsp;Qing Zhang,&nbsp;Mingjie Zhang,&nbsp;Guanqun Hu,&nbsp;Shengyuan Yu,&nbsp;Xun Han","doi":"10.1177/17448069231152129","DOIUrl":"https://doi.org/10.1177/17448069231152129","url":null,"abstract":"<p><p><b>Background</b>: Migraine is a common type of primary headache with disabling brain dysfunction. It has been found that pituitary adenylate cyclase activating polypeptide (PACAP) is involved in the pathogenesis of migraine, however, the role of PACAP and its receptors in chronic migraine remains unclear. Therefore, the present study aimed to explore the changes of PACAP and its receptors in different duration after recurrent dural inflammation soup stimulations and to investigate the co-expression between PACAP and calcitonin gene-related peptide (CGRP). <b>Methods</b>: Adult male rats were implanted with cannula surrounding superior sagittal sinus, which was followed by dural infusion of inflammatory soup (IS) or normal saline (NS). The rats were randomly divided into 4 groups (<i>n</i> = 8 for each group): IS stimulation for seven days (IS-7 group), IS stimulation for 14 days (IS-14 group), IS stimulation for 21 days (IS-21 group), and NS control for 21 days (CON group). The facial mechanical withdrawal threshold was daily measured during the whole experiment. The behavioral changes (ipsilateral and bilateral face grooming behavior) in a plastic cage of rats were observed and recorded. The expression of PACAP, its receptors (PAC1, VPAC1, VPAC2), and CGRP in the trigeminal ganglia (TG) and the trigeminal nucleus caudalis (TNC) was examined by immunohistochemistry. Immunofluorescence was used to explore the co-expression of PACAP, PAC1 receptor, and CGRP after repeated IS administration in the TG. <b>Results</b>: The ipsilateral facial grooming time of IS-21 group displayed an apparent increase than CON group after repeated stimulation on day 2, while significant differences were observed on day 14. No differences were found between the IS-21 and CON group in bilateral facial grooming. Dural IS stimulation induced a significantly decrease in facial mechanical withdrawal thresholds. PACAP positive cells in the regions of TNC were gradually decreased with the IS days increasing. PACAP and PAC1 receptor expression in the TG had a trend of increasing first and then decreasing. There was no significant difference in expression of VPAC1 and VPAC2 in the TG and the TNC. Immunofluorescence showed that PACAP was mainly expressed in TG neurons. PACAP and PAC1 receptor co-expression decreased gradually after repetitive IS stimulation. While the co-expression between PACAP and CGRP reached the peak in IS-7 group after repetitive IS stimulation, and then decreased. <b>Conclusions</b>: This study demonstrated that repetitive chemical stimulations induced a gradual decrease of PACAP in the TNC, while the PACAP and PAC1 receptor expression in TG showed dynamical changes of increasing first and then decreasing after repeated IS administration. These results suggested exhaustion of PACAP could be involved in the duration of chronic migraine and implied PACAP may contribute to the pathology of migraine through the PAC1 receptor, which was associated with CG","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/0a/10.1177_17448069231152129.PMC9869212.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9193321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemokine CCL7 mediates trigeminal neuropathic pain <i>via</i> CCR2/CCR3-ERK pathway in the trigeminal ganglion of mice.","authors":"Lin-Peng Zhu, Meng-Lin Xu, Bao-Tong Yuan, Ling-Jie Ma, Yong-Jing Gao","doi":"10.1177/17448069231169373","DOIUrl":"10.1177/17448069231169373","url":null,"abstract":"<p><strong>Background: </strong>Chemokine-mediated neuroinflammation plays an important role in the pathogenesis of neuropathic pain. The chemokine CC motif ligand 7 (CCL7) and its receptor CCR2 have been reported to contribute to neuropathic pain via astrocyte-microglial interaction in the spinal cord. Whether CCL7 in the trigeminal ganglion (TG) involves in trigeminal neuropathic pain and the involved mechanism remain largely unknown.</p><p><strong>Methods: </strong>The partial infraorbital nerve transection (pIONT) was used to induce trigeminal neuropathic pain in mice. The expression of <i>Ccl7</i>, <i>Ccr1</i>, <i>Ccr2</i>, and <i>Ccr3</i> was examined by real-time quantitative polymerase chain reaction. The distribution of CCL7, CCR2, and CCR3 was detected by immunofluorescence double-staining. The activation of extracellular signal-regulated kinase (ERK) was examined by Western blot and immunofluorescence. The effect of CCL7 on neuronal excitability was tested by whole-cell patch clamp recording. The effect of selective antagonists for CCR1, CCR2, and CCR3 on pain hypersensitivity was checked by behavioral testing.</p><p><strong>Results: </strong><i>Ccl7</i> was persistently increased in neurons of TG after pIONT, and specific inhibition of CCL7 in the TG effectively relieved pIONT-induced orofacial mechanical allodynia. Intra-TG injection of recombinant CCL7 induced mechanical allodynia and increased the phosphorylation of ERK in the TG. Incubation of CCL7 with TG neurons also dose-dependently enhanced the neuronal excitability. Furthermore, pIONT increased the expression of CCL7 receptors <i>Ccr1</i>, <i>Ccr2</i>, and <i>Ccr3</i>. The intra-TG injection of the specific antagonist of CCR2 or CCR3 but not of CCR1 alleviated pIONT-induced orofacial mechanical allodynia and reduced ERK activation. Immunostaining showed that CCR2 and CCR3 are expressed in TG neurons, and CCL7-induced hyperexcitability of TG neurons was decreased by antagonists of CCR2 or CCR3.</p><p><strong>Conclusion: </strong>CCL7 activates ERK in TG neurons via CCR2 and CCR3 to enhance neuronal excitability, which contributes to the maintenance of trigeminal neuropathic pain. CCL7-CCR2/CCR3-ERK pathway may be potential targets for treating trigeminal neuropathic pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/08/d0/10.1177_17448069231169373.PMC10413901.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9976553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sound-induced analgesia cannot always be observed in adult mice.","authors":"Qi-Yu Chen,&nbsp;Jinjin Wan,&nbsp;Mianxian Wang,&nbsp;Shanshan Hong,&nbsp;Min Zhuo","doi":"10.1177/17448069231197158","DOIUrl":"10.1177/17448069231197158","url":null,"abstract":"<p><p>Music seems promising as an adjuvant pain treatment in humans, while its mechanism remains to be illustrated. In rodent models of chronic pain, few studies reported the analgesic effect of music. Recently, Zhou et al. stated that the analgesic effects of sound depended on a low (5 dB) signal-to-noise ratio (SNR) relative to ambient noise in mice. However, despite employing multiple behavioral analysis approaches, we were unable to extend these findings to a mice model of chronic pain listening to the 5 dB SNR.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/00/2a/10.1177_17448069231197158.PMC10467218.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10127227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sophoridine alleviates hyperalgesia and anxiety-like behavior in an inflammatory pain mouse model induced by complete freund's adjuvant.","authors":"Zheng Rong,&nbsp;Le Yang,&nbsp;Yue Chen,&nbsp;Yan Qin,&nbsp;Cai-Yan Cheng,&nbsp;Jun Zhao,&nbsp;Long-Fei Li,&nbsp;Xue Ma,&nbsp;Yu-Mei Wu,&nbsp;Shui-Bing Liu,&nbsp;Yan-Ni Liang,&nbsp;Ming-Gao Zhao","doi":"10.1177/17448069231177634","DOIUrl":"https://doi.org/10.1177/17448069231177634","url":null,"abstract":"<p><p>Chronic pain, along with comorbid psychiatric disorders, is a common problem worldwide. A growing number of studies have focused on non-opioid-based medicines, and billions of funds have been put into digging new analgesic mechanisms. Peripheral inflammation is one of the critical causes of chronic pain, and drugs with anti-inflammatory effects usually alleviate pain hypersensitivity. Sophoridine (SRI), one of the most abundant alkaloids in Chinese herbs, has been proved to exert antitumor, antivirus and anti-inflammation effects. Here, we evaluated the analgesic effect of SRI in an inflammatory pain mouse model induced by complete Freund's adjuvant (CFA) injection. SRI treatment significantly decreased pro-inflammatory factors release after LPS stimuli in microglia. Three days of SRI treatment relieved CFA-induced mechanical hypersensitivity and anxiety-like behavior, and recovered abnormal neuroplasticity in the anterior cingulate cortex of mice. Therefore, SRI may be a candidate compound for the treatment of chronic inflammatory pain and may serve as a structural basis for the development of new drugs.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/16/d8/10.1177_17448069231177634.PMC10201643.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9514254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polysorbate 80 blocked a peripheral sodium channel, Na_v1.7, and reduced neuronal excitability.","authors":"Ryeong-Eun Kim,&nbsp;Jin-Sung Choi","doi":"10.1177/17448069221150138","DOIUrl":"https://doi.org/10.1177/17448069221150138","url":null,"abstract":"<p><p>Polysorbate 80 is a non-ionic detergent derived from polyethoxylated sorbitan and oleic acid. It is widely used in pharmaceuticals, foods, and cosmetics as an emulsifier. Na_v1.7 is a peripheral sodium channel that is highly expressed in sympathetic and sensory neurons, and it plays a critical role in determining the threshold of action potentials (APs). We found that 10 μg/mL polysorbate 80 either abolished APs or increased the threshold of the APs of dorsal root ganglions. We thus investigated whether polysorbate 80 inhibits Na_v1.7 sodium current using a whole-cell patch-clamp recording technique. Polysorbate 80 decreased the Na_v1.7 current in a concentration-dependent manner with a half-maximal inhibitory concentration (IC₅₀) of 250.4 μg/mL at a holding potential of -120 mV. However, the IC₅₀ was 1.1 μg/mL at a holding potential of -90 mV and was estimated to be 0.9 μg/mL at the resting potentials of neurons, where most channels are inactivated. The activation rate and the voltage dependency of activation of Na_v1.7 were not changed by polysorbate 80. However, polysorbate 80 caused hyperpolarizing shifts in the voltage dependency of the steady-state fast inactivation curve. The blocking of Na_v1.7 currents by polysorbate 80 was not reversible at a holding potential of -90 mV but was completely reversible at -120 mV, where the channels were mostly in the closed state. Polysorbate 80 also slowed recovery from inactivation and induced robust use-dependent inhibition, indicating that it is likely to bind to and stabilize the inactivated state. Our results indicate that polysorbate 80 inhibits Na_v1.7 current in concentration-, state-, and use-dependent manners when used even below commercial concentrations. This suggests that polysorbate 80 may be helpful in pain medicine as an excipient. In addition, <i>in vitro</i> experiments using polysorbate 80 with neurons should be conducted with caution.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/db/69/10.1177_17448069221150138.PMC9829885.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10645664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urolithin A alleviates neuropathic pain and activates mitophagy.","authors":"Chenyi Wang,&nbsp;Zizhu Wang,&nbsp;Shiyu Xue,&nbsp;Yutong Zhu,&nbsp;Jiahao Jin,&nbsp;Qiuyu Ren,&nbsp;Xiaodong Shi","doi":"10.1177/17448069231190815","DOIUrl":"10.1177/17448069231190815","url":null,"abstract":"<p><p>Neuropathic pain (NP) occurs frequently in the general population and has a negative impact on the quality of life. There is no effective therapy available yet owing to the complex pathophysiology of NP. In our previous study, we found that urolithin A (UA), a naturally occurring microflora-derived metabolite, could relieve NP in mice by inhibiting the activation of microglia and release of inflammation factors. Here in this study, we sought to investigate whether mitophagy would be activated when UA alleviated NP in mice. We showed that the autophagy flow was blocked in the spinal dorsal horn of the chronic constriction injury (CCI) mice when the most obvious pain behavior occurs. Intraperitoneal injection of UA markedly activated the mitophagy mediated by PTEN-induced kinase 1/Parkin, promoted mitobiogenesis in both neurons and microglia, and alleviated NP in the CCI mice. In summary, our data suggest that UA alleviates NP in mice and meanwhile induces mitophagy activation, which highlights a therapeutic potential of UA in the treatment of NP.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ef/cb/10.1177_17448069231190815.PMC10387767.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10293633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compartmentalized primary cultures of dorsal root ganglion neurons to model peripheral pathophysiological conditions.","authors":"Simona Giorgi,&nbsp;Angela Lamberti,&nbsp;Laura Butrón,&nbsp;Olivia Gross-Amat,&nbsp;David Alarcón-Alarcón,&nbsp;Enrique Rodríguez-Cañas,&nbsp;Asia Fernández-Carvajal,&nbsp;Antonio Ferrer Montiel","doi":"10.1177/17448069231197102","DOIUrl":"10.1177/17448069231197102","url":null,"abstract":"Neurosensory disorders such as pain and pruritus remain a major health problem greatly impacting the quality of life, and often increasing the risk of mortality. Current pre-clinical models to investigate dysfunction of sensory neurons have shown a limited clinical translation, in part, by failing to mimic the compartmentalized nociceptor anatomy that exhibits a central compartment containing the soma and a peripheral one harboring the axon endings with distinct molecular and cellular environmental composition. Thus, there is a need to validate compartmentalized preclinical neurosensory models for investigating the pathophysiology of peripheral sensory disorders and to test drug candidates. Here, we have addressed this issue and developed a microfluidic-based preclinical nociceptor model and validated it for investigating inflammatory and neuropathic peripheral disorders. We show that this model reproduces the peripheral sensitization and resolution produced by an inflammatory soup and by the chemotherapeutic drug paclitaxel. Furthermore, compartmentalized nociceptor primary cultures were amenable to co-culture with keratinocytes in the axonal compartment. Interaction of axonal endings with keratinocytes modulated neuronal responses, consistent with a crosstalk between both cell types. These findings pave the way towards translational pre-clinical sensory models for skin pathophysiological research and drug development.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/42/bd/10.1177_17448069231197102.PMC10521292.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10362729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic screen identifies the natural product silymarin as a novel anti-inflammatory analgesic.","authors":"Daniel M DuBreuil, Xiaofan Lai, Kevin Zhu, Gracesenia Chahyadinata, Caroline Perner, Brenda M Chiang, Ashley Battenberg, Caroline L Sokol, Brian J Wainger","doi":"10.1177/17448069221148351","DOIUrl":"10.1177/17448069221148351","url":null,"abstract":"<p><p>Sensory neuron hyperexcitability is a critical driver of pathological pain and can result from axon damage, inflammation, or neuronal stress. G-protein coupled receptor signaling can induce pain amplification by modulating the activation of Trp-family ionotropic receptors and voltage-gated ion channels. Here, we sought to use calcium imaging to identify novel inhibitors of the intracellular pathways that mediate sensory neuron sensitization and lead to hyperexcitability. We identified a novel stimulus cocktail, consisting of the SSTR2 agonist L-054,264 and the S1PR3 agonist CYM5541, that elicits calcium responses in mouse primary sensory neurons <i>in vitro</i> as well as pain and thermal hypersensitivity in mice <i>in vivo</i>. We screened a library of 906 bioactive compounds and identified 24 hits that reduced calcium flux elicited by L-054,264/CYM5541. Among these hits, silymarin, a natural product derived from milk thistle, strongly reduced activation by the stimulation cocktail, as well as by a distinct inflammatory cocktail containing bradykinin and prostaglandin E2. Silymarin had no effect on sensory neuron excitability at baseline, but reduced calcium flux via Orai channels and downstream mediators of phospholipase C signaling. <i>In vivo</i>, silymarin pretreatment blocked development of adjuvant-mediated thermal hypersensitivity, indicating potential use as an anti-inflammatory analgesic.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/65/10.1177_17448069221148351.PMC9893088.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10698918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of immune cells to cancer-related neuropathic pain: An updated review.","authors":"He Ma,&nbsp;Zhenxiang Pan,&nbsp;Bingjie Lai,&nbsp;Mingyue Li,&nbsp;Jingping Wang","doi":"10.1177/17448069231182235","DOIUrl":"https://doi.org/10.1177/17448069231182235","url":null,"abstract":"<p><p>Given that the incidence of cancer is dramatically increasing nowadays, cancer-related neuropathic pain including tumor-related and therapy-related pain gradually attracts more attention from researchers, which basically behaves as a metabolic-neuro-immune disorder with worse clinical outcomes and prognosis. Among various mechanisms of neuropathic pain, the common underlying one is the activation of inflammatory responses around the injured or affected nerve(s). Innate and adaptive immune reactions following nerve injury together contribute to the regulation of pain. On the other hand, the tumor immune microenvironment involving immune cells, as exemplified by lymphocytes, macrophages, neutrophils and dendritic cells, inflammatory mediators as well as tumor metastasis have added additional characteristics for studying the initiation and maintenance of cancer-related neuropathic pain. Of interest, these immune cells in tumor microenvironment exert potent functions in promoting neuropathic pain through different signaling pathways. To this end, this review mainly focuses on the contribution of different types of immune cells to cancer-related neuropathic pain, aims to provide a comprehensive summary of how these immune cells derived from the certain tumor microenvironment participate in the pathogenesis of neuropathic pain. Furthermore, the clarification of roles of various immune cells in different tumor immune microenvironments associated with certain cancers under neuropathic pain states constitutes innovative biology that takes the pain field in a different direction, and thereby provides more opportunities for novel approaches for the prevention and treatment of cancer-related neuropathic pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f2/0d/10.1177_17448069231182235.PMC10262651.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9993996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}