Brain-stem relays mediating stimulation-produced antinociception from the lateral hypothalamus in the rat

Several lines of evidence have demonstrated a role for the lateral hypothalamus (LH) in an endogenous system of descending inhibition. The present study, in rats lightly anesthetized with pentobarbital, was undertaken to examine systematically the organization in the brain stem of pathways mediating descending inhibition of the nociceptive tail flick (TF) reflex produced by focal electrical stimulation in the LH. The microinjection of lidocaine into the midbrain, dorsolateral pons, or medial medulla resulted in significant increases in stimulation thresholds in the LH for inhibition of the TF reflex (89.1, 67.4, and 73.6%, respectively). Selective lesions of cell bodies in the midbrain or medulla by the neurotoxin ibotenic acid also produced significant increases in stimulation thresholds in the LH for inhibition of the TF reflex (31.6 and 131.6%, respectively), thus revealing relays in the periaqueductal gray and the nucleus raphe magnus located between the LH and the lumbar spinal cord. The failure of ibotenic acid to affect LH-produced descending inhibition when microinjected into the dorsolateral pons, and the significant effect produced by lidocaine microinjected into the same area, implicates fibers of passage in the dorsolateral pons in descending inhibition of the TF reflex produced by focal electrical stimulation in the LH. The fluorescent dye Fast blue and HRP conjugated to wheat germ agglutinin were used to confirm that the area stimulated in the LH has reciprocal connections with the periaqueductal gray and nucleus raphe magnus.