Role of [Ca2+]i in the ATP-induced heat sensitization process of rat nociceptive neurons

Role of [Ca2+], in the ATP-induced heat sensitization process of rat nociceptive neurons. J. Neurophysiol. 81: 2612-,2619, 1999. 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+],) levels a with the calcium ionophore ionomycin (10 mu M). Similar results were obtained in experiments employing [Ca2+], release from preloaded "caged calcium" (NITR-5/AM I) via UV photolysis. In both cases, sensitization was prevented by preventing rises in [Ca2+], with the membrane-permeant calcium chelator BAPTA-AM ii mM. No pronounced change of mechanical sensitivity was observed. Heat-induced membrane currents (I-heat) 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+], resulted in reversible sensitization of I-heat. In the same subject of DRG neurons,the endogenous algogen ATP (100 mu M) was used to elevate [Ca2+](i) which again resulted in significant sensitization of I-heat. 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+], 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.