A role for ASIC3 in the modulation of high-intensity pain stimuli.
Acid-sensing ion channel 3 (ASIC3), a proton-gated ion channel of the degenerins/epithelial sodium channel (DEG/ENaC) receptor family is expressed predominantly in sensory neurons including nociceptive neurons responding to protons. To study the role of ASIC3 in pain signaling, we generated ASIC3 knockout mice. Mutant animals were healthy and responded normally to most sensory stimuli. However, in behavioral assays for pain responses, ASIC3 null mutant mice displayed a reduced latency to the onset of pain responses, or more pain-related behaviors, when stimuli of moderate to high intensity were used. This unexpected effect seemed independent of the modality of the stimulus and was observed in the acetic acid-induced writhing test (0.6 vs. 0.1-0.5%), in the hot-plate test (52.5 and 55 vs. 50 degrees C), and in tests for mechanically induced pain (tail-pinch vs. von Frey filaments). We postulate that ASIC3 is involved in modulating moderate- to high-intensity pain sensation.
Chen
Chih-Cheng
CC
Laboratory of Genetics, National Institute of Mental Health, 36 Convent Drive 3D06, Bethesda, MD 20892, USA.
Zimmer
Anne
A
Sun
Wei-Hsin
WH
Hall
Jennifer
J
Brownstein
Michael J
MJ
Zimmer
Andreas
A
D062565:Acid Sensing Ion Channels; D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal; D017931:DNA Primers; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D010146:Pain / Q000503:physiopathology*; D010812:Physical Stimulation; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*
C112231:ASIC3 protein, human; D062565:Acid Sensing Ion Channels; D017931:DNA Primers; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015222:Sodium Channels