Spinal GABA(B)-receptor antagonism increases nociceptive transmission in vivo.
GABA(B) receptors modulate primary afferent fibre evoked responses of spinal neurones. Here effects of the selective GABA(B) receptor antagonist, CGP-35348, on electrically-evoked responses of spinal neurones in control and carrageenan-inflamed rats were studied. Spinal CGP-35348 (0.1-10 microg/50 microl) did not alter Abeta- or Adelta-fibre evoked neuronal responses in control rats, although C-fibre evoked responses and post discharge responses of spinal neurones were significantly facilitated by 3.0 and 10.0 microg/50 microl CGP-35348 (p < 0.05). In carrageenan-treated animals, spinal CGP-35348 did not alter electrically evoked responses of spinal neurones at any dose. Our data suggest that following acute peripheral inflammation there is loss of endogenous GABA(B) receptor mediated inhibition of C-fibre transmission at the level of the spinal cord.
Sokal
D M
DM
School of Biomedical Sciences, E Floor, Medical School, University of Nottingham, Nottingham NG7 2UH, UK.
Chapman
V
V
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002351:Carrageenan / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018756:GABA Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D018080:Receptors, GABA-B / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D002351:Carrageenan