title: Roles of ASIC3, TRPV1, and NaV1.8 in the transition from acute to chronic pain in a mouse model of fibromyalgia.
abstract: BACKGROUND
  Tissue acidosis is effective in causing chronic muscle pain. However, how muscle nociceptors contribute to the transition from acute to chronic pain is largely unknown.
  
  
  RESULTS
  Here we showed that a single intramuscular acid injection induced a priming effect on muscle nociceptors of mice. The primed muscle nociceptors were plastic and permitted the development of long-lasting chronic hyperalgesia induced by a second acid insult. The plastic changes of muscle nociceptors were modality-specific and required the activation of acid-sensing ion channel 3 (ASIC3) or transient receptor potential cation channel V1 (TRPV1). Activation of ASIC3 was associated with increased activity of tetrodotoxin (TTX)-sensitive voltage-gated sodium channels but not protein kinase Cϵ (PKCϵ) in isolectin B4 (IB4)-negative muscle nociceptors. In contrast, increased activity of TTX-resistant voltage-gated sodium channels with ASIC3 or TRPV1 activation in NaV1.8-positive muscle nociceptors was required for the development of chronic hyperalgesia. Accordingly, compared to wild type mice, NaV1.8-null mice showed briefer acid-induced hyperalgesia (5 days vs. >27 days).
  
  
  CONCLUSIONS
  ASIC3 activation may manifest a new type of nociceptor priming in IB4-negative muscle nociceptors. The activation of ASIC3 and TRPV1 as well as enhanced NaV1.8 activity are essential for the development of long-lasting hyperalgesia in acid-induced, chronic, widespread muscle pain.
authors: Wei-Nan
authors: WN
authors: Chen
authors: Cheng-Han
authors: CH
authors: Lee
authors: Shing-Hong
authors: SH
authors: Lin
authors: Chia-Wen
authors: CW
authors: Wong
authors: Wei-Hsin
authors: WH
authors: Sun
authors: John N
authors: JN
authors: Wood
authors: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan. chih@ibms.sinica.edu.tw.
authors: Chih-Cheng
authors: CC
authors: Chen
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D059787:Acute Pain / Q000209:etiology* / Q000378:metabolism; D000814:Aniline Compounds / Q000627:therapeutic use; D000818:Animals; D002478:Cells, Cultured; D059350:Chronic Pain / Q000209:etiology* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005356:Fibromyalgia / Q000139:chemically induced / Q000150:complications*; D005663:Furans / Q000627:therapeutic use; D005727:Ganglia, Spinal / Q000166:cytology; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000187:drug effects; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000627:therapeutic use; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C520740:A 803467; C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels; D000814:Aniline Compounds; D004791:Enzyme Inhibitors; D005663:Furans; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568318:Scn10a protein, mouse; D026941:Sodium Channel Blockers; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse