mu- but not delta- and kappa-opioid receptors in the ventrolateral orbital cortex mediate opioid-induced antiallodynia in a rat neuropathic pain model.
Previous studies have indicated that the ventrolateral orbital cortex (VLO) is involved in opioid-mediated antinociception in the tail flick test and formalin test. The aim of the current study was to examine the effect of opioids microinjected into the VLO on allodynia in the rat L5/L6 spinal nerve ligation (SNL) model of neuropathic pain and determine the roles of different subtypes of opioid receptors in this effect. The allodynia was assessed by both mechanical (von Frey filaments) and cold plate (4 degrees C) stimuli. Morphine (1.0, 2.5, and 5.0 microg) microinjected into the VLO contralateral to the nerve ligation dose-dependently depressed the mechanical and cold allodynia and these effects were reversed by nonselective opioid receptor antagonist naloxone (1.0 microg) administrated into the same site. Microinjection of endomorphin-1 (5.0 microg), a highly selective mu-opioid receptor agonist, and [D-Ala2, D-Leu5]-enkephalin (DADLE, 10 microg), a delta-/mu-opioid receptor agonist, also depressed the allodynia, and the effects of both drugs were blocked by selective mu-receptor antagonist beta-funaltrexamine (beta-FNA, 3.75 microg), but the effects of DADLE were not influenced by the selective delta-receptor antagonist naltrindole (5.0 microg). Microinjection of U-62066 (100 microg), a kappa-opioid receptor agonist, into the VLO had no effect on the allodynia. These results suggest that the VLO is involved in opioid-induced antiallodynia and mu- but not delta- and kappa-opioid receptor mediates these effects in the rat with neuropathic pain.
Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, People's Republic of China.
Mei
M
Zhao
Jun-Yang
JY
Wang
Hong
H
Jia
Jing-Shi
JS
Tang
D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000523:psychology*; D010147:Pain Measurement / Q000379:methods; D010812:Physical Stimulation; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000150:complications; D013997:Time Factors
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009020:Morphine