L-dopa abolishes thermal and mechanical hyperalgesia in the rat model of neuropathic pain

Introduction: Biogenic amines participate in a nociceptive-modulatory network present in the central and in the autonomie nervous system. Dopamine modulates central nociceptive mechanism and, acting as an inhibitory neurotransmitter, it also modulates sympathetic ganglionic transmission. Several painful states are associated with an increase in activity of the sympathetic nervous system. In this presentation, we explore whether it is possible to modulate the hyperalgesia present in the rat model of neuropathic pain by increasing the availability of dopamine in inhibitory dopaminergic neurons Methods: After protocol approval by the Institutional Animal Care and Research Committee, twenty three adult male Sprague Dawley rats (250-350g) were anesthetized with intraperitoneal pentobarbital. Four loose ligatures were placed around the sciatic nerve on one hind paw and a sham operation was performed on the other hind paw. Thermal hyperalgesia was determined by comparing the latency of hind paw withdrawal to noxious heat stimulation (radiant heat source, 50 degree C)or the frequency of paw-withhdrawal after application of acetone (cold hyperalgesia) to the sciatic nerve-ligated and non ligated hind paw. Mechanical hyperalgesia was determined by comparing the threshold to mechanical stimulation in the sciatic-ligated and non ligated paws using calibrated von Frey filaments. The dopamine precursor L-Dopa (200mg/kg, plus a Dopa decarboxylase inhibitor, Sinemet)) was injected intraperitoneally every 48-72 hours, starting 14 days after surgery. Hyperalgesia was determined 48-72 hours after each administration of the drug and inmediately before the administration of the next dose. Results: Mechanical and thermal hyperalgesia developed fifteen days after loose ligation of the sciatic nerve. The administration of L-Dopa produces a long lasting (up to five days) suppression of mechanical, heat and cold hyperalgesia. No behavioral changes attributable to the administration of L-Dopa were observed. The effect of L-Dopa is antagonized by Haloperidol. Discussion; Dopamine is a neurotransmitter present in inhibitory interneurons both in the sympathetic and the central nervous system and it is involved in the modulation of nociception and in the transmission of information through the sympathetic ganglia. A decrease in dopaminergic influences may result in an increase in nociception and in sympathetic activity. L-Dopa selectively restores the dopamine content in depleted dopaminergic neurons in the central nervous system and in the sympathetic ganglia. It is proposed that neuropathic pain may be associated to changes in the dopaminergic system and that the prolonged effect of L-Dopa decreasing hyperalgesia may be mediated through the replenishment of dopamine stores in inhibitory interneurons.