title: Acid mediates a prolonged antinociception via substance P signaling in acid-induced chronic widespread pain.
abstract: BACKGROUND
  Substance P is an important neuropeptide released from nociceptors to mediate pain signals. We recently revealed antinociceptive signaling by substance P in acid-sensing ion channel 3 (ASIC3)-expressing muscle nociceptors in a mouse model of acid-induced chronic widespread pain. However, methods to specifically trigger the substance P antinociception were still lacking.
  
  
  RESULTS
  Here we show that acid could induce antinociceptive signaling via substance P release in muscle. We prevented the intramuscular acid-induced hyperalgesia by pharmacological inhibition of ASIC3 and transient receptor potential V1 (TRPV1). The antinociceptive effect of non-ASIC3, non-TRPV1 acid signaling lasted for 2 days. The non-ASIC3, non-TRPV1 acid antinociception was largely abolished in mice lacking substance P. Moreover, pretreatment with substance P in muscle mimicked the acid antinociceptive effect and prevented the hyperalgesia induced by next-day acid injection.
  
  
  CONCLUSIONS
  Acid could mediate a prolonged antinociceptive signaling via the release of substance P from muscle afferent neurons in a non-ASIC3, non-TRPV1 manner.
authors.forename: Wei-Nan
authors.initials: WN
authors.lastname: Chen
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan. chih@ibms.sinica.edu.tw.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chen
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism; D000143:Acids / Q000633:toxicity*; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D059350:Chronic Pain / Q000139:chemically induced* / Q000378:metabolism* / Q000517:prevention & control; D003064:Cnidarian Venoms / Q000008:administration & dosage; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism; D010147:Pain Measurement; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000172:deficiency* / Q000235:genetics; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: C501880:APETx2 protein, Anthopleura elegantissima; C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels; D000143:Acids; D003064:Cnidarian Venoms; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D013373:Substance P; C071423:capsazepine; D002211:Capsaicin