Acetylsalicylic acid (ASA) is thought to exert its peripheral analgesic effects via inhibition of cyclooxygenase. We now studied the effects of ASA on heat responses in primary nociceptive neurons by whole-cell patch-clamp and calcium microfluorimetry experiments. Heat-evoked inward currents in acutely dissociated rat dorsal root ganglion neurons were significantly reduced by ASA in a dose-dependent and reversible manner (IC(50) 375 nM, Hill slope -2.2, maximum effect 55%). Heat-evoked calcium transients (measured with FURA-2) were reversibly reduced by 53+/-14% (P<0.05) by co-application of 1 microM ASA. The low IC(50) value, the rapid occurrence, and the reversibility of the observed effects make it unlikely that inhibition of prostaglandin synthesis is involved in the inhibition of nociceptive heat responses by ASA, and suggest a more direct effect on heat transduction mechanisms.
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