Lesion of the bulbospinal noradrenergic pathways blocks desipramine-induced inhibition of the C-fiber evoked nociceptive reflex in rats

Desipramine-induced inhibition of spinal cord nociceptive transmission was studied in rats with or without lesion of the bulbospinal noradrenergic sys tem by recording the C-fiber evoked nociceptive reflex from a hind limb. Bu lbospinal noradrenergic projections were lesioned by injecting intrathecall y 20 mug of 6-hydroxydopamine 2 weeks before the electrophysiological exper iments. Results show that desipramine (5, 10 and 20 mg/kg intraperitoneally ) produced dose-dependent inhibition of the C reflex response duration in r ats having intact noradrenergic bulbospinal systems. The inhibitory effect of desipramine was reduced or even abolished in rats pre-treated with 6-hyd roxydopamine. In addition, [H-3]-noradrenaline uptake was significantly low er in spinal cord slices arising from 6-hydroxydopamine lesioned animals, a s compared to that from intact rats. These observations support the notion that the antinociceptive activity of antidepressants with noradrenergic sel ectivity depends on a normal rate of endogenous noradrenaline released by b ulbospinal neurons. (C) 2001 Elsevier Science ireland Ltd. All rights reser ved.