Barbiturate-induced inhibition of a spinal nociceptive reflex: role of GABA mechanisms and descending modulation.
The present study investigated the effect of systemically administered pentobarbital on the tail-flick (TF) reflex in rats, the neurochemical mechanism of action and the role of descending influences. Pentobarbital produced a clear inhibition of the TF response. Systemic administration of naloxone did not significantly alter this effect, thus it appears to be independent of endogenous opioid systems. Complete spinal transection resulted in a marked potentiation of pentobarbital-induced TF inhibition, demonstrating a spinal locus of action. Moreover, this observation suggests the existence of a tonic descending excitatory influence, opposing the pentobarbital-produced depression of nociceptive transmission in the intact animal. Intrathecal administration of pentobarbital caused a much more pronounced TF inhibition in transected than in intact animals, lending further support to this hypothesis. To identify the neurochemical mechanisms involved in pentobarbital-produced antinociception, the gamma-aminobutyric acid (GABA) antagonists bicuculline and picrotoxinin were administered intrathecally in spinalized animals. Both substances caused an attenuation of the pentobarbital effect, demonstrating the involvement of GABAergic transmission. The proposed descending excitatory system may act either presynaptically and cause a decreased release of GABA into the synapse or postsynaptically via endogenous GABA antagonistic neurotransmitters, which may change the conformation of the GABA-barbiturate receptor complex.
D000700:Analgesics; D000818:Animals; D003864:Depression, Chemical; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000700:Analgesics; D005680:gamma-Aminobutyric Acid; D010424:Pentobarbital