title: The pH response of rat cutaneous nociceptors correlates with extracellular [Na+] and is increased under amiloride.
abstract: 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.
authors.affiliation: Klinik und Poliklinik für Dermatoglie der Universität Bonn, Klinische Dermatophysiologie, Germany. khsteen@mailer.meb.uni-bonn.de
authors.forename: K H
authors.initials: KH
authors.lastname: Steen
authors.forename: H
authors.initials: H
authors.lastname: Wegner
authors.forename: P W
authors.initials: PW
authors.lastname: Reeh
mesh_terms: 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*
chemical_list: D000584:Amiloride; D006859:Hydrogen; D012964:Sodium