Spinal monoamine and opiate systems partly mediate the antinociceptive effects produced by glutamate at brainstem sites.

The administration of the excitatory amino acid glutamate into the periaqueductal gray (PAG) or ventromedial medulla (VM) resulted in a reliable, short lasting elevation in the tail flick and hot plate response latencies in rats. The prior intrathecal administration of methysergide (30 micrograms) or phentolamine (30 micrograms) into the lumbar space produced a significant antagonism of the elevated tail flick reflex latencies evoked by glutamate given into the PAG and VM. Intrathecal naloxone (10 micrograms) significantly antagonized the effects on tail flick produced by VM, but not PAG, injections of glutamate. No intrathecal treatment significantly antagonized the effects of intracerebral glutamate on the supraspinally organized hot plate response. These results indicate that the excitation of glutamate-receptor linked systems in the PAG and VM exert a powerful antireflexive effect on spinal processing by the activation of spinopetal monoamine pathways, but that their mechanisms do not totally overlap as the VM systems also directly or indirectly activate a naloxone sensitive link in the spinal cord. The failure to antagonize the supraspinally organized hot plate response by intrathecal antagonists indicates that aside from an effect (if any) on spinal sensory processing, these brainstem systems may also act at the supraspinal level to actively modulate the animal's response to an otherwise aversive somatic stimulus.