Morphine-induced and stimulation-produced analgesias at coincident periaqueductal central gray loci: Evaluation of analgesic congruence, tolerance, and cross-tolerance

Abstract

The analgesias produced by intracranial morphine (5 μg) and focal brain stimulation (120 μA) applied at virtually coincident periaqueductal central gray loci were evaluated for congruence of efficacious analgesia-producing sites. In general, the ventrocaudal periaqueductal central gray was found to be most sensitive to both analgesia-producing manipulations. Both morphine and stimulation produced significant analgesic effects in hot plate, tail flick, and pinch analgesiometric test procedures when applied in that region. However, morphine was most efficacious when administered medially within the central gray whereas stimulation was most efficacious when applied at its ventrolateral edge. The experiments also considered the development of tolerance and cross-tolerance between these two analgesia-producing manipulations. A reduction in the efficacy of focal brain stimulation in the hot plate and tail flick tests was apparent upon its second application 3 days after the first. The efficacy of morphine was also attenuated after its second microinjection 3 days later. Regarding the development of cross-tolerance between the two analgesia-producing treatments, morphine's efficacy was attenuated in the hot plate test and that of stimulation was attenuated in the tail flick test when these treatments were preceded by stimulation and morphine, respectively. Although stimulation- and morphine-sensitive sites overlap, cross-tolerance between these two analgesia-producing manipulations applied at central loci would not be expected to develop because the most sensitive morphine and stimulation sites are not congruent.