Inhibitory effects of spinal baclofen on spinal dorsal horn neurones in inflamed and neuropathic rats in vivo.
gamma-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter, which modulates afferent transmission of nociceptive information at different levels of the central nervous system. Plasticity of spinal GABAergic systems may contribute to aberrant nociceptive responses associated with inflammatory and neuropathic pain states. Here potential changes in spinal GABA(B) receptor function in rats with peripheral inflammation and nerve injury, compared to control were investigated. Extracellular recordings of electrically evoked responses of spinal dorsal horn neurones were made in halothane anaesthetised rats. Effects of spinal administration of the GABA(B) receptor agonist baclofen (0.1-10 microg/50 microL) on evoked responses of spinal neurones in control, hindpaw carrageenan inflamed, spinal nerve ligated and sham-operated rats were studied. In all groups of rats, spinal baclofen significantly reduced Abeta-, Adelta- and C-fibre evoked responses of spinal dorsal horn neurones in a dose related manner. Spinal pre-administration of the GABA(B) receptor antagonist, CGP-35348 (30 microg/50 microL) significantly blocked the inhibitory effects of baclofen on evoked neuronal responses in control rats. Estimated ED(50) values for each fibre type within experimental groups were calculated, a significant (P<0.05) difference between the values for Abeta-fibre-evoked and C-fibre mediated post-discharge responses of spinal dorsal horn neurones in spinal nerve ligated rats is reported. This finding may reflect decreased sensitivity of Abeta-fibre-evoked responses to baclofen, as well as an increased sensitivity of post-discharge responses to baclofen in spinal nerve ligated rats. Overall, we report that GABA(B)-receptor control of A- and C-fibre evoked responses of spinal neurones is not profoundly altered in models of inflammatory and neuropathic pain.
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002351:Carrageenan; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004594:Electrophysiology; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013127:Spinal Nerves / Q000293:injuries*
D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; C066430:CGP 35348; D002351:Carrageenan; D001418:Baclofen