The combined effects of N-type calcium channel blockers and morphine on A delta versus C fiber mediated nociception

Intrathecal mu opiates produce analgesia presynaptically by inhibiting calc ium ion influx and postsynaptically by increasing potassium flux. Mu recept ors are expressed on presynaptic terminals of unmyelinated (C), but not mye linated (A delta) nociceptors. Thus, mu -opioids such as morphine may act p resynaptically to inhibit C, but not A delta ,neurotransmission, and postsy naptically on dorsal horn cells that receive input from A delta and/or C fi ber nociceptors. N-type calcium ion channel blockers, such as omega -conoto xin GVIA. (omega -CTX), produce analgesia by impeding flux of calcium ions into A delta and C fiber nociceptor terminals. Thus, morphine and omega -CT X attenuated C fiber nociception additively, possibly indicating the same p resynaptic site of action. Conversely, morphine and omega- CTX were supraad ditively analgesic on an A delta test, indicating that these agents probabl y have different sites of action. We conclude that although intrathecal app lication of either morphine or omega -CTX attenuates both A delta and C fib er mediated nociception in rats, the combined effects are quite different f or the two fiber types. Specifically, although coadministration of morphine with omega -CTX produces an additive, apparently presynaptic antinocicepti on for C fiber-mediated responses, the combination produces a clearly supra additive, and likely synergistic effect on A delta mediated nociception, pr obably by acting at pre and postsynaptic sites, respectively.