Is Acid Painful or not?

Abstract

Acid (or proton) is an effective algogen to excite primary afferent nociceptors and evoke pain. Pain associated with tissue acidosis occurs where there is/are tissue injury, inflammation, ischemia, fatiguing exercise, or tumors. However, a recent study in mice has virtually changed our view regarding the significance of acid signaling in nociception. In the study, an acid-induced muscle pain model was used to probe the endogenous antinociceptive signaling pathway. Surprisingly, instead of acid-induced pain, the authors discovered that acid could also elicit an antinociceptive effect on mice, when specific acid sensors of muscle nociceptors, such as ASIC3 and TRPV1, were blocked. The acid-mediated antinociceptive pathway might act via a subset of acid-sensitive muscle afferent neurons to release substance P (SP), which would act on neurokinin 1 (NK1) receptors to reduce acid-induced depolarization via activation of an M-type potassium channel. The newly uncovered antinociceptive role for acid has largely changed our concept of pain biology and brought new insight for the analgesic drug development.