Delimitation of neuronal substrates necessary for the analgesic action of baclofen and morphine.

The loci of neuronal substrates necessary for the analgesic action of baclofen and of morphine were determined by systematic transection of the rat cerebrospinal axis. Severe reduction in the analgesic capacity of both drugs, assessed with the tail flick test, occurred after section of the thoracic spinal cord, indicating that necessary substrates are located rostral to this level. These data also suggest that baclofen-induced analgesia does not primarily result from a pharmacological blockade of nociceptive information at the first sensory synapse in the spinal cord. Neither baclofen- nor morphine-induced analgesia was altered by transection of the brain stem between the superior and inferior colliculi, but the action of both drugs was greatly reduced following section of the medulla 3 mm rostral to the obex. Thus, the rostral margin of neuronal substrates mediating the effects of both drugs lies somewhere in the pons or anterior third of the medulla. This observation is compatible with the notion that analgesia induced by baclofen and morphine involves, at least in part, common neuronal substrates.