Intracerebroventricular treatment of mice with pertussis toxin induces hyperalgesia and enhances 3H-nitrendipine binding to synaptic membranes: Similarity with morphine tolerance

Summary The effect of intracerebroventricular treatment of mice with pertussis toxin (PTX) on pain perception and ³H-nitrendipine binding was examined to study a possible change in the GTP-binding proteins in morphine tolerant rodents. It was observed that both PTX treatment and chronic administration of morphine cause hyperalgesia in the acetic acid-induced writhing test. Analgesic effects brought by the acute administration of morphine or nifedipine, a calcium antagonist, were not affected by PTX treatment. In synaptic membrane fractions prepared from mice treated with PTX or morphine chronically, specific binding of ³H-nitrendipine was enhanced approximately 41.8% and 35.7%, respectively, without alteration in its affinity. Chronic administration of morphine followed by PTX treatment did not display further increases in ³H-nitrendipine binding.These results suggest that the PTX-sensitive GTP-binding proteins may not be involved in the manifestation of the analgesic effect of morphine in mice.Abbreviation PTX Pertussis toxinSend offprint requests to T. Ohnishi at the above address