{"title":"巨噬细胞来源的HMGB1作为致痛分子/治疗靶点在内脏疼痛中的作用","authors":"Maho Tsubota, A. Kawabata","doi":"10.11154/PAIN.34.24","DOIUrl":null,"url":null,"abstract":"Accumulating evidence sheds light on the crucial role of a neuroimmune crosstalk in neurogenic inflammation and diverse neurological diseases associated with neuro inflammation. High mobility group box 1 (HMGB 1 ), one of damage–associated molecular patterns (DAMPs) ⁄ alarmins, is now considered a pro–inflammatory ⁄ pro– nociceptive molecule, and participates in the pathogenesis of neuropathic and inflammatory pain. In this review, we focus on the role of HMGB 1 in visceral pain signaling in the bladder, pancreas and colon. In rodent models for cystitis–related bladder pain, macrophage–derived HMGB 1 activates the receptor for advanced glycation end– products (RAGE), and induces NF– κ B–dependent overexpression of cystathionine– γ –lyase, an H 2 S–generating enzyme, resulting in excessive excitation of nociceptors through the H 2 S ⁄ Ca v 3 . 2 T–type calcium channel pathway and subsequent bladder pain. The macrophage–derived HMGB 1 also appears to play a role in the development of pancreatic pain accompanying acute pancreatitis and of colonic pain in a mouse model for irritable bowel syndrome (IBS). Thus, HMGB 1 is considered a key mediator for a neuroimmune crosstalk involved in visceral pain signaling in the bladder, pancreas and colon, and may serve as a novel therapeutic target for treatment of visceral pain in patients with interstitial cystitis ⁄ bladder pain syndrome, acute pancreatitis or IBS.","PeriodicalId":41148,"journal":{"name":"Pain Research","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2019-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Role of macrophage–derived HMGB1 as an algogenic molecule ⁄ therapeutic target in visceral pain\",\"authors\":\"Maho Tsubota, A. Kawabata\",\"doi\":\"10.11154/PAIN.34.24\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Accumulating evidence sheds light on the crucial role of a neuroimmune crosstalk in neurogenic inflammation and diverse neurological diseases associated with neuro inflammation. High mobility group box 1 (HMGB 1 ), one of damage–associated molecular patterns (DAMPs) ⁄ alarmins, is now considered a pro–inflammatory ⁄ pro– nociceptive molecule, and participates in the pathogenesis of neuropathic and inflammatory pain. In this review, we focus on the role of HMGB 1 in visceral pain signaling in the bladder, pancreas and colon. In rodent models for cystitis–related bladder pain, macrophage–derived HMGB 1 activates the receptor for advanced glycation end– products (RAGE), and induces NF– κ B–dependent overexpression of cystathionine– γ –lyase, an H 2 S–generating enzyme, resulting in excessive excitation of nociceptors through the H 2 S ⁄ Ca v 3 . 2 T–type calcium channel pathway and subsequent bladder pain. The macrophage–derived HMGB 1 also appears to play a role in the development of pancreatic pain accompanying acute pancreatitis and of colonic pain in a mouse model for irritable bowel syndrome (IBS). Thus, HMGB 1 is considered a key mediator for a neuroimmune crosstalk involved in visceral pain signaling in the bladder, pancreas and colon, and may serve as a novel therapeutic target for treatment of visceral pain in patients with interstitial cystitis ⁄ bladder pain syndrome, acute pancreatitis or IBS.\",\"PeriodicalId\":41148,\"journal\":{\"name\":\"Pain Research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2019-03-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pain Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.11154/PAIN.34.24\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pain Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.11154/PAIN.34.24","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Role of macrophage–derived HMGB1 as an algogenic molecule ⁄ therapeutic target in visceral pain
Accumulating evidence sheds light on the crucial role of a neuroimmune crosstalk in neurogenic inflammation and diverse neurological diseases associated with neuro inflammation. High mobility group box 1 (HMGB 1 ), one of damage–associated molecular patterns (DAMPs) ⁄ alarmins, is now considered a pro–inflammatory ⁄ pro– nociceptive molecule, and participates in the pathogenesis of neuropathic and inflammatory pain. In this review, we focus on the role of HMGB 1 in visceral pain signaling in the bladder, pancreas and colon. In rodent models for cystitis–related bladder pain, macrophage–derived HMGB 1 activates the receptor for advanced glycation end– products (RAGE), and induces NF– κ B–dependent overexpression of cystathionine– γ –lyase, an H 2 S–generating enzyme, resulting in excessive excitation of nociceptors through the H 2 S ⁄ Ca v 3 . 2 T–type calcium channel pathway and subsequent bladder pain. The macrophage–derived HMGB 1 also appears to play a role in the development of pancreatic pain accompanying acute pancreatitis and of colonic pain in a mouse model for irritable bowel syndrome (IBS). Thus, HMGB 1 is considered a key mediator for a neuroimmune crosstalk involved in visceral pain signaling in the bladder, pancreas and colon, and may serve as a novel therapeutic target for treatment of visceral pain in patients with interstitial cystitis ⁄ bladder pain syndrome, acute pancreatitis or IBS.