Blockade by calcium antagonists of chemical excitation and sensitization of polymodal nociceptors in the cat's cornea.
1. The possibility that a modified Ca2+ channel mediates chemical and thermal excitation of nociceptors was examined in single polymodal nociceptive fibres of the cat's cornea. 2. Ca2+ channel blockers cadmium (2.5 mM) and diltiazem (1 mM), and high external [Ca2+] (40 mM), markedly reduced nociceptive responses to topical acidic solutions (pH 4.5). 3. Decreasing the pH to 6.5 did not cause excitation, but reduced the subsequent response to pH 4.5 buffer. 4. Diltiazem (1 mM), applied after repeated stimulation with stepped heating pulses (35 to 47-49 degrees C in 2 degrees C steps) decreased the impulse responses elicited by heat. The decrease in threshold to thermal stimulation produced by repeated heating was blocked by diltiazem. 5. Mechanical threshold and mechanical responsiveness of corneal polymodal nociceptors was not modified by Ca2+ antagonists or by a high-Ca2+ solution. 6. These results offer indirect evidence that proton-activated Ca2+ channels mediate stimulation of nociceptors by acidic solutions. The same type of ionic channel appears to be involved in the response of nociceptors to heat and in sensitization, but not in their responsiveness to mechanical stimulation. The blockade of nociceptive responses by Ca2+ antagonists opens the possibility of using Ca2+ blockers as selective analgesic drugs.
Pozo
M A
MA
Instituto de Neurociencias, Universidad de Alicante, Spain.
Gallego
R
R
Gallar
J
J
Belmonte
C
C
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002415:Cats; D003315:Cornea / Q000294:innervation*; D004110:Diltiazem / Q000494:pharmacology; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*
D015220:Calcium Channels; D002104:Cadmium; D004110:Diltiazem; D002118:Calcium