title: Analgesic Effect of Electroacupuncture in a Mouse Fibromyalgia Model: Roles of TRPV1, TRPV4, and pERK.
abstract: Fibromyalgia (FM) is among the most common chronic pain syndromes encountered in clinical practice, but there is limited understanding of FM pathogenesis. We examined the contribution of transient receptor potential vanilloid 1 (TRPV1) and TRPV4 channels to chronic pain in the repeated acid injection mouse model of FM and the potential therapeutic efficacy of electroacupuncture. Electroacupuncture (EA) at the bilateral Zusanli (ST36) acupoint reduced the long-lasting mechanical hyperalgesia induced by repeated acid saline (pH 4) injection in mouse hindpaw. Isolated L5 dorsal root ganglion (DRG) neurons from FM model mice (FM group) were hyperexcitable, an effect reversed by EA pretreatment (FM + EA group). The increase in mechanical hyperalgesia was also accompanied by upregulation of TRPV1 expression and phosphoactivation of extracellular signal regulated kinase (pERK) in the DRG, whereas DRG expression levels of TRPV4, p-p38, and p-JNK were unaltered. Blockade of TRPV1, which was achieved using TRPV1 knockout mice or via antagonist injection, and pERK suppressed development of FM-like pain. Both TRPV1 and TRPV4 protein expression levels were increased in the spinal cord (SC) of model mice, and EA at the ST36 acupoint decreased overexpression. This study strongly suggests that DRG TRPV1 overexpression and pERK signaling, as well as SC TRPV1 and TRPV4 overexpression, mediate hyperalgesia in a mouse FM pain model. The therapeutic efficacy of EA may result from the reversal of these changes in pain transmission pathways.
authors.affiliation: College of Chinese Medicine, School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Jaung-Geng
authors.initials: JG
authors.lastname: Lin
authors.affiliation: College of Chinese Medicine, Graduate Institute of Integrative Medicine, China Medical University, Taichung 40402, Taiwan; China Medical University Hospital, Department of Chinese Medicine, Taichung, 40402, Taiwan; Research Center for Chinese Medicine & Acupuncture, China Medical University, Taichung 40402, Taiwan.
authors.forename: Ching-Liang
authors.initials: CL
authors.lastname: Hsieh
authors.affiliation: Research Center for Chinese Medicine & Acupuncture, China Medical University, Taichung 40402, Taiwan; College of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Lin
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D015671:Electroacupuncture; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005356:Fibromyalgia / Q000188:drug therapy* / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D050916:TRPV Cation Channels / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000700:Analgesics; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C486576:Trpv4 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases