The pH response of rat cutaneous nociceptors correlates with extracellular[Na+] and is increased under amiloride

Excess hydrogen ions induce sustained nociceptor excitation as well as pain , and this has been suggested, with evidence from sensory ganglion cells, t o result from gating a slowly inactivating sodium/calcium inward current. I n the rat skin-nerve preparation, isolated receptive fields of pH-sensitive C-fibre terminals were exposed to low-pH solutions of various sodium conce ntrations. The pH responses showed a good correlation with log [Na+](e), wh ich supports the above model. Amiloride has previously been shown to block a pH-induced Na+ current involved in sensory transduction in hamster taste cells; however, it has been shown to act differently in cutaneous nocicepto rs. Amiloride induced a dose-dependent increase in and prolongation of the nociceptive pH responses, with a prominent acceleration of the onset. The l atter could be mimicked by replacing external sodium with sucrose, thus imp eding sodium-proton antiport. Together, the findings indicate functional ex pression of amiloride-sensitive Na+/H+-antiporters, which enable the nocice ptive nerve endings to extrude invading H+. Intracellular acidification may thus compete with Na+/H+ exchange, and pH(i) may be decisive in the transd uction of nociception and pain from tissue acidosis.