title: Mice lacking acid-sensing ion channels (ASIC) 1 or 2, but not ASIC3, show increased pain behaviour in the formalin test.
abstract: Extracellular acidification is a component of the inflammatory process and may be a factor driving the pain accompanying it. Acid-sensing ion channels (ASICs) are neuronal proton sensors and evidence suggests they are involved in signalling inflammatory pain. The aims of this study were to (1) clarify the role of ASICs in nociception and (2) confirm their involvement in inflammatory pain and determine whether this was subunit specific. This was achieved by (1) direct comparison of the sensitivity of ASIC1, ASIC2, ASIC3 and TRPV1 knockout mice versus wildtype littermates to acute thermal and mechanical noxious stimuli and (2) studying the behavioural responses of each transgenic strain to hind paw inflammation with either complete Freund's adjuvant (CFA) or formalin. Naïve ASIC1(-/-) and ASIC2(-/-) mice responded normally to acute noxious stimuli, whereas ASIC3(-/-) mice were hypersensitive to high intensity thermal stimuli. CFA injection decreased mechanical and thermal withdrawal thresholds for up to 8 days. ASIC2(-/-) mice had increased mechanical sensitivity on day 1 post-CFA compared to wildtype controls. TRPV1(-/-) mice had significantly reduced thermal, but not mechanical, hyperalgesia on all days after inflammation. Following formalin injection, ASIC1(-/-) and ASIC2(-/-), but not ASIC3(-/-) or TRPV1(-/-), mice showed enhanced pain behaviour, predominantly in the second phase of the test. These data suggest that whilst ASICs may play a role in mediating inflammatory pain, this role is likely to be modulatory and strongly dependent on channel subtype.
authors.affiliation: London Pain Consortium, Wolfson CARD, King's College London, Guy's Campus, London, UK.
authors.forename: Amelia A
authors.initials: AA
authors.lastname: Staniland
authors.forename: Stephen B
authors.initials: SB
authors.lastname: McMahon
mesh_terms: D062565:Acid Sensing Ion Channels; D000818:Animals; D001522:Behavior, Animal; D005557:Formaldehyde; D005620:Freund's Adjuvant; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D010146:Pain / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics* / Q000502:physiology*; D050916:TRPV Cation Channels / Q000235:genetics / Q000502:physiology
chemical_list: C568266:ASIC1 protein, human; C568267:ASIC1 protein, mouse; C568265:ASIC2 protein, mouse; D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D005557:Formaldehyde; D012313:RNA; D005620:Freund's Adjuvant