Depression of NMDA-receptor-mediated segmental transmission by ketamine and ketoprofen, but not L-NAME, on the in vitro neonatal rat spinal cord preparation.

Activation of spinal N-methyl-D-aspartate (NMDA) receptors and then the nitric oxide and the arachidonic acid pathways is important in pain transmission. This study assessed the effects of the NMDA receptor channel blocker ketamine, the nitric oxide synthase inhibitor L-NAME, and the cyclooxygenase inhibitor ketoprofen in nociceptive transmission using an in vitro neonatal rat spinal cord preparation. Supramaximal electrical stimulation of the dorsal root evoked the A-fibre- and C-fibre-mediated high intensity excitatory postsynaptic potential (EPSP) in the ipsilateral ventral root. Low intensity stimulation evoked the A-fibre-mediated monosynaptic compound action potential (MSR) superimposed on the low intensity EPSP. Both the low intensity EPSP and the high intensity EPSP contain NMDA-receptor-mediated components. Only ketamine and ketoprofen depressed the synaptic responses. Ketamine depressed all three spinal reflexes with IC(50) values (with 95% CI) of 10.80 microM (5.97 to 19.54 microM) for the MSR, 8.29 microM (4.53 to 14.17 microM) for the low intensity EPSP, and 5.35 microM (3.05 to 9.40 microM) for the high intensity EPSP. Ketoprofen depressed the low intensity EPSP and the high intensity EPSP only; IC(50) values (with 95% CI) were 354.5 microM (217.5 to 576.8 microM) and 302.7 microM (174.0 to 526.7 microM), respectively. Reflexes recovered after drug washout. These data demonstrated that ketamine and ketoprofen, but not L-NAME, depressed NMDA-mediated nociceptive transmission in spinal cord preparations from neonatal rats.