Morphine applied to the ventrolateral orbital cortex produces a naloxone-reversible antinociception in the rat.

Our previous findings have indicated that the ventrolateral orbital cortex (VLO) may be involved in modulation of nociception and plays an important role as a higher center of an endogenous analgesic system (a feedback loop) consisting of spinal cord-nucleus submedius (Sm)-VLO-periaqueductal gray (PAG)-spinal cord. To further investigate the neurotransmitter mechanism involved in this nociceptive modulatory pathway, we tested the effects of microinjection of morphine (5 microg, 0.5 microl) into VLO on the tail flick (TF) reflex. The results show that a unilateral microinjection of morphine into VLO dose-dependently suppresses the TF reflex. Furthermore, 6 min after termination of morphine injection, microinjection of opioid receptor antagonist naloxone (1.5 microg, 0.5 microl) into the same VLO site reverses this morphine-evoked inhibition of TF reflex. These results suggest that morphine application to the VLO may directly or indirectly activate VLO neurons projecting to the PAG through the opioid receptor mediation leading to activation of the brainstem descending inhibitory system and depression of the nociceptive inputs at the spinal cord level.