Pretreatment with cholera or pertussis toxin differentially modulates morphine- and beta-endorphin-induced...

The present study was designed to examine the possible involvement of supraspinal CTX- and PTX-sensitive G-proteins in an opioid-induced antinociception in the formalin test. Morphine (1 microg) and beta-endorphin (1 microg) given i.c.v. displayed near-maximal inhibitory effects against the formalin response in the first (0-5 min) and the second (20-40 min) phases. CTX (0.1-0.5 microg) pretreated i.c.v. produced antinociceptive effects in both phases of the formalin responses. Its effect was more pronounced in the first phase. However, PTX (0.05-0.5 microg) injected i.c.v produced the antinociceptive effect only in the first, but not the second, phase. Both CTX (0.5 microg) and PTX (0.5 microg), at the dose which had no intrinsic effect, significantly reversed the beta-endorphin-induced antinociceptive effect observed during the second, but not the first, phase. However, the antinociceptive effect by morphine failed to be affected by the same dose of treatment with CTX or PTX. Our results indicate that, at the supraspinal level, CTX- and PTX-sensitive G-proteins appear to be involved in the modulation of antinociception induced by supraspinally administered beta-endorphin, but not morphine, in the formalin pain model.