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, to result from gating a slowly inactivating sodium/calcium inward current. In the rat skin-nerve preparation, isolated receptive fields of pH-sensitive C-fibre terminals were exposed to low-pH solutions of various sodium concentrations. The pH responses showed a good correlation with log [Na+]e, which 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 nociceptors. Amiloride induced a dose-dependent increase in and prolongation of the nociceptive pH responses, with a prominent acceleration of the onset. The latter could be mimicked by replacing external sodium with sucrose, thus impeding sodium-proton antiport. Together, the findings indicate functional expression of amiloride-sensitive Na+/H+-antiporters, which enable the nociceptive nerve endings to extrude invading H+. Intracellular acidification may thus compete with Na+/H+ exchange, and pHi may be decisive in the transduction of nociception and pain from tissue acidosis.
Steen
K H
KH
Klinik und Poliklinik für Dermatoglie der Universität Bonn, Klinische Dermatophysiologie, Germany. khsteen@mailer.meb.uni-bonn.de
Wegner
H
H
Reeh
P W
PW
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008297:Male; D009411:Nerve Endings / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000294:innervation*; D012964:Sodium / Q000172:deficiency / Q000378:metabolism*
D000584:Amiloride; D006859:Hydrogen; D012964:Sodium