Partial involvement of monoamines and opiates in the inhibition of rat spinal nociceptive neurons evoked by stimulation in midbrain periaqueductal gray or lateral reticular formation.

In rats anesthetized with sodium pentobarbital, we tested the effects of systemic or intrathecal administration of the opiate antagonist naloxone, the serotonergic antagonist methysergide, or the adrenergic antagonist phentolamine, on inhibition produced by electrical stimulation in midbrain periaqueductal gray (PAG) or lateral reticular formation (LRF) of the responses of single lumbar dorsal horn neurons to noxious heating (50-54 degrees C, 10 s) of hindpaw skin. Systemically administered naloxone (1-10 mg/kg i.v.) reduced (greater than 20% below predrug inhibition) inhibition from PAG and/or LRF in 5/12 units and had no effect in the remainder. Systemic methysergide (2-6 mg/kg i.v.) selectively reduced PAG-evoked inhibition in 6 units, while inhibitions from both PAG and LRF stimulation were reduced in one unit and unaffected in 8 units. Systemic phentolamine (2-4 mg/kg) reduced LRF-evoked inhibition in 4 units, while inhibitions from PAG and LRF were reduced in one unit and unaffected in 5. Intrathecally applied methysergide reduced or abolished PAG-evoked inhibition in 8/16 units and reduced or abolished LRF-evoked inhibition in 6/14 units. Reductions in the level of inhibition were reversible in one-half of the cases, whereas they persisted for over 2 h in the remainder. The mixed effects of both systemically and intrathecally administered drugs suggest that monoamines and opiates may be partly involved in spinal inhibitory mechanisms activated from the midbrain.