Striatal dopamine D2 receptors attenuate neuropathic hypersensitivity in the rat

Abstract

Earlier studies indicate that striatal dopamine D2 receptors are involved in pain regulation in non-neuropathic conditions. We assessed whether striatal dopamine D2 receptors contribute to pain regulation also in neuropathic conditions. The spared nerve injury model of neuropathy was induced by unilateral ligation of the tibial and common peroneal nerves in the rat. In awake nerve-injured animals, pain-related withdrawal responses to calibrated monofilaments or noxious heating were attenuated following striatal administration of a dopamine D2 receptor agonist quinpirole. Pain-related responses were attenuated only in the nerve-injured limb ipsilateral to the injection and in the midline (tail). In unoperated controls, striatal administration of quinpirole at an antihypersensitive dose did not influence withdrawal responses to mechanical stimulation. Attenuation of pain-related responses induced by striatal administration of quinpirole was reversed by intrathecal administration of a dopamine D2 receptor antagonist (eticlopride) or a non-selective 5-HT receptor antagonist (methysergide), but not by an α2-adrenoceptor antagonist (atipamezole). In the rostroventromedial medulla of lightly anesthetized neuropathic animals, striatal administration of quinpirole significantly decreased the activity of presumably pronociceptive cells that are activated by noxious stimulation. The innocuous H-reflex in lightly anesthetized control animals was not suppressed by striatal administration of quinpirole at an antihypersensitive dose. The results indicate that striatal dopamine D2 receptors attenuate neuropathic hypersensitivity. The antihypersensitive effect induced by striatal dopamine D2 receptors in peripheral neuropathy involves suppression of impulse discharge of presumably pronociceptive neurons in the rostroventromedial medulla, and a descending influence acting on spinal 5-HT and dopamine D2 receptors. © 2007 Elsevier Inc. All rights reserved.