Striatal dopamine D2 receptors attenuate neuropathic hypersensitivity in the rat.

Abstract

Earlier studies indicate that striatal dopamine D(2) receptors are involved in pain regulation in non-neuropathic conditions. We assessed whether striatal dopamine D(2) 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 D(2) 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 D(2) receptor antagonist (eticlopride) or a non-selective 5-HT receptor antagonist (methysergide), but not by an alpha(2)-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 D(2) receptors attenuate neuropathic hypersensitivity. The antihypersensitive effect induced by striatal dopamine D(2) 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 D(2) receptors.

• Authors: Osei B Ansah, Hugo Leite-Almeida, Hong Wei, Antti Pertovaara
• Journal: Experimental neurology (Exp Neurol) Vol. 205 Issue 2 Pg. 536-46 (Jun 2007) ISSN: 0014-4886 [Print] United States
• PMID: 17451685 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dopamine Agonists
• Dopamine Antagonists
• Neurotransmitter Agents
• Receptors, Dopamine D2
• Quinpirole

Topics

• Animals
• Behavior, Animal (physiology)
• Dopamine Agonists (administration & dosage, pharmacology)
• Dopamine Antagonists (administration & dosage, therapeutic use)
• Electrophysiology
• H-Reflex (drug effects, physiology)
• Hot Temperature
• Injections, Spinal
• Male
• Medulla Oblongata (cytology, physiology)
• Microinjections
• Neostriatum (physiology)
• Neurotransmitter Agents (physiology)
• Nociceptors (drug effects, physiology)
• Pain (physiopathology)
• Peripheral Nervous System Diseases (complications)
• Physical Stimulation
• Quinpirole (pharmacology)
• Rats
• Rats, Wistar
• Receptors, Dopamine D2 (physiology)