The relative significance of spinal and supraspinal actions in the antinociceptive effect of morphine in the dorsal horn: an evaluation of the microinjection technique

Abstract

Large quantities of morphine injected directly into the brainstem of spinal anaesthetized cats inhibited the noxious heat-evoked excitation of dorsal horn neurones. The amounts required were similar to those that were required intravenously in cats with the spinal cord intact or transected. When the spinal cord was intact the amount of morphine microinjected into the brainstem required to inhibit the excitation of dorsal horn neurones was about ten fold less than it was in spinal animals. It is concluded that large, but not small doses of morphine microinjected into the brainstem can exert effects on the spinal cord after first entering the circulation. The effects of small doses are attributed to a local action in the brainstem which causes inhibition of spinal neurones either by activating descending inhibitory neuronal systems or by liberating endogenous substances which reach the spinal cord via the cerebro-spinal fluid. The concentrations of morphine achieved at various distances from the site of injection by the microinjection of microgram quantities and the time courses of the concentration changes were calculated from diffusion equations, assuming diffusion coefficients of 3 or 5 X 10(6) cm2 s-1. The curves obtained closely approximated those obtained experimentally. The concentrations achieved at distances up to 2 mm from the site of injection of 10 micrograms of morphine were calculated to exceed 10(-4)M and the time-courses of these concentration changes were compatible with the time course of inhibition of spinal neurones, or the production of analgesia after microinjection. Such concentrations are vastly in excess of those achieved in the brain after the systemic administration of morphine in analgesic doses. It is concluded that the local effects in the brainstem produced by the microinjection of microgram quantities of morphine have no relevance to the mechanism of analgesia produced by systemic administration.