A schematic model of ion channel-mediated hyperalgesic priming in muscle nociceptors. ASIC3 and TRPV1 are expressed in different subsets of muscle nociceptors with or without NaV1.8 expression. In NaV1.8-negative muscle nociceptors, ASIC3 is the major acid sensor responsible for acid-induced transient hyperalgesia and the duration of hyperalgesic priming; TRPV1 may play a minor but essential role in the nociceptor priming. In NaV1.8-positive muscle nociceptors, both ASIC3 and TRPV1 contribute to the acid-enhanced TTXr I
NaV, which is required for the establishment of priming that permits the development and maintenance of long-term hyperalgesia induced by a second acid insult. ASIC3 and TRPV1 are expressed alone or together, but ASIC3 is exclusively expressed in non-IB4 muscle nociceptors.