title: ASIC3 in muscle mediates mechanical, but not heat, hyperalgesia associated with muscle inflammation.
abstract: Peripheral initiators of muscle pain are virtually unknown, but likely key to development of chronic pain after muscle insult. The current study tested the hypothesis that ASIC3 in muscle is necessary for development of cutaneous mechanical, but not heat, hyperalgesia induced by muscle inflammation. Using mechanical and heat stimuli, we assessed behavioral responses in ASIC3-/- and ASIC3+/+ mice after induction of carrageenan muscle inflammation. ASIC3-/- mice did not develop cutaneous mechanical hyperalgesia after muscle inflammation when compared to ASIC3+/+ mice; heat hyperalgesia developed similarly between groups. We then tested if the phenotype could be rescued in ASIC3-/- mice by using a recombinant herpes virus vector to express ASIC3 in skin (where testing occurred) or muscle (where inflammation occurred). Infection of mouse DRG neurons with ASIC3-encoding virus resulted in functional expression of ASICs. Injection of ASIC3-encoding virus into muscle or skin of ASIC3-/- mice resulted in ASIC3 mRNA in DRG and protein expression in DRG and the peripheral injection site. Injection of ASIC3-encoding virus into muscle, but not skin, resulted in development of mechanical hyperalgesia similar to that observed in ASIC3+/+ mice. Thus, ASIC3 in primary afferent fibers innervating muscle is critical to development of hyperalgesia that results from muscle insult.
authors.affiliation: Graduate Program in Physical Therapy and Rehabilitation Science, 1-252 Medical Education Bldg., The University of Iowa, Iowa City, IA 52242, USA. Kathleen-sluka@uiowa.edu
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Sluka
authors.forename: Rajan
authors.initials: R
authors.lastname: Radhakrishnan
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Benson
authors.forename: Jayasheel O
authors.initials: JO
authors.lastname: Eshcol
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Price
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Babinski
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Audette
authors.forename: David C
authors.initials: DC
authors.lastname: Yeomans
authors.forename: Steven P
authors.initials: SP
authors.lastname: Wilson
mesh_terms: D062565:Acid Sensing Ion Channels; D000818:Animals; D001522:Behavior, Animal; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005727:Ganglia, Spinal / Q000166:cytology; D006930:Hyperalgesia / Q000209:etiology* / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000150:complications* / Q000209:etiology / Q000473:pathology; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D009474:Neurons / Q000502:physiology; D017288:Pain Threshold; D018408:Patch-Clamp Techniques / Q000379:methods; D010812:Physical Stimulation; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018139:Simplexvirus; D012867:Skin / Q000378:metabolism / Q000503:physiopathology; D015222:Sodium Channels / Q000172:deficiency / Q000378:metabolism*
chemical_list: C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels; D012333:RNA, Messenger; D015222:Sodium Channels