Role of [Ca2+]i in the ATP-induced heat sensitization process of rat nociceptive neurons.
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.
Kress
M
M
Institut für Physiologie und Experimentelle Pathophysiologie, Friedrich Alexander University, D91054 Erlangen-Nuremberg, Germany.
Guenther
S
S
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
D007476:Ionophores; D015759:Ionomycin; D000255:Adenosine Triphosphate; D002211:Capsaicin; D002118:Calcium