Acetylsalicylic acid reduces heat responses in rat nociceptive primary sensory neurons--evidence for a new mechanism of action.
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.
Greffrath
Wolfgang
W
Institute of Physiology and Pathophysiology, Johannes Gutenberg University, Saarstrasse 21, D-55099 Mainz, Germany.
Kirschstein
Timo
T
Nawrath
Hermann
H
Treede
Rolf-Detlef
RD
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006358:Hot Temperature; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013697:Thermosensing / Q000187:drug effects* / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D007473:Ion Channels; D001241:Aspirin; D002211:Capsaicin; D002118:Calcium