Barbiturate-induced analgesia: permissive role of a GABAA agonist

Three doses (0.025, 0.25 and 2.5 mg) of the short-acting barbiturate, pentothal, were injected intrathecally at the lumbar level of the spinal cord of female rats and did not produce analgesia in either the tail-flick latency to radiant heat (TFL) or vocalization-threshold-to-tail-shock (VTTS) tests. However, when the high dose of pentothal (2.5 mg) was given in combination with a nonanalgesia producing dose of the GABAA agonist muscimol (1 microgram), a significant and prolonged analgesia was produced in both the VTTS and TFL tests, lasting up to one hour postinjection. Intrathecal injection of the intermediate dose of pentothal (0.25 mg) in combination with 1 microgram muscimol also produced significant analgesia in the TFL but not the VTTS test. We suggest that barbiturates may act on spinal nociceptive pathways to reduce pain thresholds only when sufficient GABAergic activity is present.