The antinociceptive action of etorphine in the dorsal horn is due to a direct spinal action and not to activation of descending inhibition

Abstract

1 Etorphine, microinjected into the brainstem or administered intravenously, inhibited the firing of dorsal horn neurones to noxious heat in spinal or non-spinal anaesthetized cats and in decerebrate, non-anaesthetized cats with intact spinal cords. 2 Small doses of etorphine sometimes caused facilitation, especially when the cord was intact, but this was invariably followed by inhibition at higher doses. 3 The ED₅₀ for inhibition (mean 3.9 μg/kg) after microinjection into nucleus raphe magnus, nucleus reticularis magnocellularis or the lateral tegmental field was similar at all sites in anaesthetized, non-spinal cats. 4 The ED₅₀ for microinjection was not increased by spinal transection in anaesthetized cats (mean ED₅₀, 2.6 μg/kg) and was similar to the ED₅₀ in decerebrate, non-anaesthetized cats. 5 Intravenous administration was 2 to 3 times more effective than microinjection and the time course of inhibition was faster after intravenous administration than after microinjection. 6 It is concluded that etorphine inhibits dorsal horn neurones after microinjection or intravenous administration by a direct action on the spinal cord and not by activating a descending inhibition. After microinjection it rapidly enters the general circulation and subsequently distributes into the spinal cord. 7 It is also concluded that naloxone readily gains entry to the circulation from the brain because microinjection antagonized the effects of systemic etorphine on dorsal horn neurones in spinal cats.