title: Role of [Ca2+]i in the ATP-induced heat sensitization process of rat nociceptive neurons.
abstract: In inflamed tissue, nociceptors show increased sensitivity to noxious heat, which may account for heat hyperalgesia. In unmyelinated nociceptive afferents in rat skin in vitro, a drop of heat threshold and an increase in heat responses were induced by experimental elevation of intracellular calcium ([Ca2+]i) levels with the calcium ionophore ionomycin (10 microM). Similar results were obtained in experiments employing [Ca2+]i release from preloaded "caged calcium" (NITR-5/AM) via UV photolysis. In both cases, sensitization was prevented by preventing rises in [Ca2+]i with the membrane-permeant calcium chelator BAPTA-AM (1 mM). No pronounced change of mechanical sensitivity was observed. Heat-induced membrane currents (Iheat) were investigated with patch-clamp recordings, and simultaneous calcium measurements were performed in small sensory neurons isolated from adult rat dorsal root ganglia (DRG). Ionomycin-induced rises in [Ca2+]i resulted in reversible sensitization of Iheat. In the same subset of DRG neurons, the endogenous algogen ATP (100 microM) was used to elevate [Ca2+]i, which again resulted in significant sensitization of Iheat. In correlative recordings from the skin-nerve preparation, ATP induced heat sensitization of nociceptors, which again could be blocked by preincubation with BAPTA-AM. Rises in [Ca2+]i in response to inflammatory mediators, e.g., ATP, thus appear to play a central role in plastic changes of nociceptors, which may account for hypersensitivity of inflamed tissue.
authors.affiliation: Institut für Physiologie und Experimentelle Pathophysiologie, Friedrich Alexander University, D91054 Erlangen-Nuremberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kress
authors.forename: S
authors.initials: S
authors.lastname: Guenther
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D004594:Electrophysiology; D005260:Female; D006358:Hot Temperature; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010782:Photolysis; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000294:innervation; D013268:Stimulation, Chemical; D014466:Ultraviolet Rays
chemical_list: D007476:Ionophores; D015759:Ionomycin; D000255:Adenosine Triphosphate; D002211:Capsaicin; D002118:Calcium