Effects of topical baclofen on C fibre-evoked neuronal activity in the rat dorsal horn.
Baclofen appears to be an agonist for the bicuculline-insensitive gamma-aminobutyrateB receptors associated with C fibre terminals in the dorsal horn of the spinal cord. We have tested the effect of baclofen (applied intrathecally onto the spinal cord) on the A and C fibre-evoked responses of convergent/multireceptive neurones in the halothane-anaesthetized rat. L-Baclofen produced a dose-dependent inhibition of the C fibre- and pinch-evoked activity of these neurones which persisted for 2 h whilst the A fibre and tactile activities were little changed. The C fibre-evoked (X 3 threshold) responses were markedly or completely inhibited 10 min after doses of between 0.25 and 30 micrograms of L-baclofen (n = 21) with 0.05 micrograms causing a 48% (n = 3) and 0.01 micrograms a 28% inhibition (n = 3). D-Baclofen (30 micrograms), the inactive isomer, produced no significant changes in activity (n = 10). Bicuculline (60 micrograms) applied intrathecally before (n = 7) or after (n = 8) L-baclofen did not reverse the inhibitions. Intravenous baclofen (1-3 mg/kg) also produced neuronal inhibitions similar to the effects of intrathecal injection. The results suggest that gamma-aminobutyrateB receptors may exert a presynaptic control of C fibre afferents in the dorsal horn following intrathecal administration in the rat.
Dickenson
A H
AH
Brewer
C M
CM
Hayes
N A
NA
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects*; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*
D011963:Receptors, GABA-A; D001418:Baclofen; D001640:Bicuculline