EFFECTS OF SELECTIVE NEUROTOXIC LESION OF LUMBOSACRAL SEROTONERGIC AND NORADRENERGIC SYSTEMS ON AUTOTOMY BEHAVIOR IN RATS

Male rats underwent unilateral ligation and transection of the sciatic and saphenous nerves 2, 7 or 14 days after being injected intrathecally (at the thoracolumbar junction) with 6-hydroxydopamine (6-OHDA), 5,6-dihydroxytryptamine (5,6-DHT) or vehicle, and the development of autotomy was monitored. The effects of both neurotoxins on cervicothoracic (C5-T1) and lumbosacral (L1-S1) norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) spinal cord levels were analysed by HPLC in separate groups of rats. 6-OHDA treatment (20 mug/10 mul) produced a rapid (from day 2) and significant (90-95%) fall in NE content only at L1-S1. 5,6-DHT administration (20 mug/10 mul) produced a gradual (68%, 90% and 94%, at 2, 7 and 14 days, respectively) and selective depletion of 5-HT only at L1-S1. DA levels remained essentially unchanged after both neurotoxins. No differences in monoamine levels were detected among groups injected with vehicle. The main effects of neurotoxins on autotomy were: (1) a significant delay in the onset of autotomy in the rats injected with 6-OHDA 2 days before neurectomy; (2) a trend to autotomize earlier and more severely in the rats injected with 5,6-DHT 7 days before neurectomy and (3) an almost complete suppression of autotomy in the rats injected with 5,6-DHT 14 days before neurectomy. These results revealed that the expression of autotomy in rats can be modulated by interfering with spinal cord serotonergic activity and suggest new possible avenues for the treatment of certain specific pain diseases, such a phantom limb pain, by using selective agents capable of activating or blocking spinal cord serotonergic receptor subtypes.