Paradoxical Modulation of Nociception in Mice by Barbiturate Agonism and Antagonism: Is a GABA Site Involved in Nociception?
In a battery of four acute and chronic nociceptive tests, the GABA antagonist picrotoxin produces a uniform and sustained analgesia in mice. By contrast, barbiturates which have been presumed to act at the same receptor produce mixed and paradoxical actions. At a standard time of 10 min after drug administration a convulsant barbiturate [5-ethyl-5-(3'-methyl-but-2'-enyl)-barbituric acid] produced analgesia in three tests but had no effect in the fourth; a pure hypnotic barbiturate (amylobarbitone) produced hyperalgesia in three tests but analgesia in the fourth; while the mixed hypnotic-convulsant pentobarbitone produced hyperalgesia in two of the tests and was without any effect in the other two. There was no pattern in these results with respect to acute or chronic nociceptive tests. Surprisingly, with extended observation using the tail-flick test both pentobarbitone and the pure hypnotic (amylobarbitone) gave early hyperalgesia followed by analgesia; the convulsant barbiturate gave only analgesia. The results suggest a role for GABAA receptors in the transmission of nociceptive information; they also suggest that barbiturates act at quite a different receptor.
Carmody
John
J
School of Physiology and Pharmacology, University of New South Wales, Kensington (Sydney), NSW 2033, Australia.
Knodler
Leigh
L
Murray
Stuart
S