Enhanced thermal avoidance in mice lacking the ATP receptor P2X 3

Abstract

P2X 3 is an ATP-gated cation channel subtype expressed by a subpopulation of primary sensory neurons. In vivo spinal cord recordings in mice lacking P2X 3 ( P 2 X 3 − / − ) have suggested that this protein may be important for the coding of peripheral warm stimuli. To explore this possibility more thoroughly, we examined behavioral and electrophysiological responses to thermal stimuli in P 2 X 3 − / − mice. As previously reported, recording from the spinal cord dorsal horn of anesthetized P 2 X 3 − / − mice revealed a blunted response of wide dynamic range neurons to hind paw heating. When placed in a thermal gradient, however, P 2 X 3 − / − mice exhibited an unexpectedly enhanced avoidance of both hot and cold temperatures, relative to controls. In the tail immersion test, mutant mice exhibited shorter withdrawal latencies at temperatures above and below thermoneutrality. Consistent with these changes, P 2 X 3 − / − mice exhibited enhanced induction of spinal cord c-FOS following hind paw heating to 45 °C. Thus, gain- and loss-of-function thermosensory phenotypes coexist in P 2 X 3 − / − mice. No changes in thermal preference were observed in wild-type mice injected subcutaneously with the P2X 3 antagonist, A317491 or intrathecally with the P2X 3 and P2X 1 antagonist TNP-ATP. The reason for this apparent discrepancy is unclear, but we cannot exclude the possibility that compensatory events contribute, at least in part, to the P 2 X 3 − / − phenotype. Regardless, this study illustrates the utility of thermal preference assays as part of a comprehensive approach to the analysis of mouse thermosensation.