title: Role of orexin-2 receptors in the nucleus accumbens in antinociception induced by carbachol stimulation of the lateral hypothalamus in formalin test.
abstract: Orexins, which are mainly produced by orexin-expressing neurons in the lateral hypothalamus (LH), play an important role in pain modulation. Previously, it has been established that the nucleus accumbens (NAc) is involved in the modulation of formalin-induced nociceptive responses, a model of tonic pain. In this study, the role of intra-accumbal orexin-2 receptors (OX2rs) in the mediation of formalin-induced pain was investigated. A volume of 0.5 μl of 10, 20, and 40 nmol/l solutions of TCS OX2 29, an OX2r antagonist, were unilaterally microinjected into the NAc 5 min before an intra-LH carbachol microinjection (0.5 μl of 250 nmol/l solution). After 5 min, animals received a subcutaneous injection of formalin 2.5% (50 μl) into the hind paw. Pain-related behaviors were assessed at 5 min intervals during a 60-min test period. The findings showed that TCS OX2 29 administration dose dependently blocked carbachol-induced antinociception during both phases of formalin-induced pain. The antianalgesic effect of TCS OX2 29 was greater during the late phase compared with the early phase. These observations suggest that the NAc, as a part of a descending pain-modulatory circuitry, partially mediates LH-induced analgesia in the formalin test through recruitment of OX2rs. This makes the orexinergic system a good potential therapeutic target in the control of persistent inflammatory pain.
authors.affiliation: aNeuroscience Research Center, Shahid Beheshti University of Medical Sciences bDepartment of Toxicology & Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Yazdi
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Jahangirvand
authors.forename: Somayeh
authors.initials: S
authors.lastname: Ezzatpanah
authors.forename: Abbas
authors.initials: A
authors.lastname: Haghparast
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000378:metabolism; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D000068796:Orexin Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D064446:Orexin Receptors / Q000187:drug effects* / Q000378:metabolism; D000068797:Orexins / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000473:pathology; D010147:Pain Measurement; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C572065:1-(3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinyl)-3,3-dimethyl-2-((4-pyridinylmethyl)amino)-1-butanone; D018712:Analgesics, Non-Narcotic; D007546:Isoquinolines; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D011725:Pyridines; D002217:Carbachol