The relevance of cholinergic transmission at the spinal level to opiate effectiveness

Rats chronically implanted with intrathecal catheters displayed a dose-dependent increase in the hot-place and tail-flick response latencies following the injection of morphine or nicomorphine into the subarachnoid space through the indwelling catheter. Naloxone inhibited the antinociceptive effect of both opiate drugs, but the inhibition of nicomorphine-induced antinociception was incomplete. To evaluate the importance of cholinergic mechanisms in opiate effectiveness, the interactions with atropine or physostigmine were evaluated. Atropine reduced the effects of morphine and abolished the effects of nicomorphine at the doses used. Physostigmine markedly potentiated morphine effectiveness, but had a negligible effect on nicomorphine effectiveness. It is proposed that these differences relate to a specific cholinergic mechanism involved in antinociception after intrathecal nicomorphine. The data indicate that at a spinal level cholinergic mechanisms are relevant to opiate effectiveness.