The roles of different subtypes of opioid receptors in mediating the nucleus submedius opioid-evoked antiallodynia in a neuropathic pain model of rats

Previous studies have indicated that thalamic nucleus submedius is involved in opioid-mediated antinociception in tail flick test and formalin test. The current study examined the effects of opioids microinjected into the thalamic nucleus submedius on the allodynia developed in neuropathic pain model rats, and determined the roles of different subtypes of opioid receptors in the thalamic nucleus submedius opioid-evoked antiallodynia. The allodynic behaviors induced by L5/L6 spinal nerve ligation were assessed by mechanical (von Frey filaments) and cold (4 degrees C plate) stimuli. Morphine (1.0, 2.5, and 5.0 mu g) microinjected into the thalamic nucleus submedius contralateral to the nerve injury paw produced a dose-dependent inhibition of the mechanical and cold allodynia, and these effects were reversed by microinjection of the non-selective opioid receptor antagonist naloxone (1.0 mu g) into the same site. Microinjection of endomorphin-1 (5.0 mu g), a highly selective mu-opioid receptor agonist, and [D-Ala 2, D-Leu(5)]-enkephalin (10 mu g), a delta-/mu-opioid receptor agonist, also inhibited the allodynic behaviors, and these effects were blocked by selective mu-opioid receptor antagonist beta-funaltrexamine hydrochloride (3.75 mu g). However, the [D-Ala(2), D-Leu(5)]-enkephalin-evoked antiallodynic effects were not influenced by the selective delta-opioid receptor antagonist naltrindole (5.0 jug). Microinjection of the selective kappa-receptor agonist spiradoline mesylate salt (100 mu g) into the thalamic nucleus submedius failed to alter the allodynia induced by spinal nerve ligation. These results suggest that the thalamic nucleus submedius is involved in opioid-evoked antiallodynia which is mediated by mu- but not delta- and kappa-Opioid receptor in the neuropathic pain model rats. (C) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.