Meloxicam selectively depresses the afterdischarge of rat spinal dorsal horn neurones in response to noxious stimulation

Abstract

This study examined the effects of the cyclooxygenase-2 (COX-2) inhibitor, meloxicam, on responses of spinal dorsal horn neurones to synaptic inputs in vivo. Experiments were run using male Sprague–Dawley rats (350–375 g) anesthetized with Na-pentobarbital (50 mg/kg, i.p.) and acutely spinalized at T9. Spinal segments L1–4 were exposed for extracellular single unit recording of on-going and stimulation-evoked activity of eight wide dynamic range neurones. On-going activity was unaffected by meloxicam (0.1 mg/kg, i.v.). However, responses to noxious mechanical stimulation (21 N for 3 s) of the cutaneous receptive field of the hind paw were depressed by meloxicam in particular the afterdischarge (34.50±6.06% inhibition) in all eight neurones studied. The brief initial discharge in response to stimulation was depressed less (15.31±4.89% inhibition, n=7/8). The data indicate that the percent inhibition of the afterdischarge was significantly greater than that of the initial discharge ( P<0.05). Given the selectivity of meloxicam for COX-2, the data suggest that COX-2 may be involved in mediating and/or modulating excitatory effects of nociceptive inputs to dorsal horn neurones, in particular the prolonged stimulation-evoked afterdischarge.