Junjie Chen1, Parisa Hasanein2, Alireza Komaki3, Siamak Yari4. 1. Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 226001, China. 2. Department of Biology, School of Basic Sciences, University of Zabol, Po. Box: 98615-538, Zabol, 9861335856, Iran. p.hasanein@uoz.ac.ir. 3. Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. 4. Department of Biology, School of Basic Sciences, Bu-Ali Sina University, Hamedan, Iran.
Abstract
RATIONALE: Nucleus cuneiformis (NC), a reticular nucleus of the midbrain, is a part of the descending pain modulatory system and therefore has an important role in pain perception. OBJECTIVES: Considering the abundance of GABAA and cannabinoid receptors in the NC and also the bidirectional roles for GABA in controlling nociception, the present study examined the effects of bilateral intra-NC microinjection of different doses of the GABAA receptor agonist, muscimol, and the GABAA receptor antagonist, bicuculline, on pain modulation using formalin test. We also assessed interaction between canabinergic and GABAergic systems in the NC during this test. METHODS: Rats were exposed to intra-NC microinjection of bicuculline (50,100, and 200 ng/side) or muscimol (60, 120, and 240 ng/side) and then subjected to the formalin test. In another set of experiments, the effects of muscimol (60 ng/side) or bicuculline (50 ng/side) administration 5 min before a cannabinoid receptor agonist WIN 55,212-2 (5, 10, and 20 μg/side) microinjection into NC on the formalin test were evaluated. RESULTS: Microinjection of bicuculline and muscimol into the NC decreased and increased pain responses, respectively, in a dose-dependent manner during both phases of the test. Microinjection of WIN 55,212-2 into the NC significantly reduced pain responses in a dose-dependent manner. Microinjection of bicuculline or muscimol in combination with WIN 55,212-2 into the NC respectively potentiated and attenuated WIN 55,212-2-induced antinociception in the formalin test. CONCLUSIONS: This study shows that GABA in the NC is involved in pain modulation and suggests the existence of a GABAA-mediated inhibitory system in the NC on pain control. Furthermore, it seems that the antinociceptive effect of WIN 55,212-2 in the formalin test is mediated partly by the activity of local GABAA receptors in the NC.
RATIONALE: Nucleus cuneiformis (NC), a reticular nucleus of the midbrain, is a part of the descending pain modulatory system and therefore has an important role in pain perception. OBJECTIVES: Considering the abundance of GABAA and cannabinoid receptors in the NC and also the bidirectional roles for GABA in controlling nociception, the present study examined the effects of bilateral intra-NC microinjection of different doses of the GABAA receptor agonist, muscimol, and the GABAA receptor antagonist, bicuculline, on pain modulation using formalin test. We also assessed interaction between canabinergic and GABAergic systems in the NC during this test. METHODS:Rats were exposed to intra-NC microinjection of bicuculline (50,100, and 200 ng/side) or muscimol (60, 120, and 240 ng/side) and then subjected to the formalin test. In another set of experiments, the effects of muscimol (60 ng/side) or bicuculline (50 ng/side) administration 5 min before a cannabinoid receptor agonist WIN 55,212-2 (5, 10, and 20 μg/side) microinjection into NC on the formalin test were evaluated. RESULTS: Microinjection of bicuculline and muscimol into the NC decreased and increased pain responses, respectively, in a dose-dependent manner during both phases of the test. Microinjection of WIN 55,212-2 into the NC significantly reduced pain responses in a dose-dependent manner. Microinjection of bicuculline or muscimol in combination with WIN 55,212-2 into the NC respectively potentiated and attenuated WIN 55,212-2-induced antinociception in the formalin test. CONCLUSIONS: This study shows that GABA in the NC is involved in pain modulation and suggests the existence of a GABAA-mediated inhibitory system in the NC on pain control. Furthermore, it seems that the antinociceptive effect of WIN 55,212-2 in the formalin test is mediated partly by the activity of local GABAA receptors in the NC.
Authors: Renato Leonardo de Freitas; Carlos José Salgado-Rohner; Jaime Eduardo Cecílio Hallak; José Alexandre de Souza Crippa; Norberto Cysne Coimbra Journal: Int J Neuropsychopharmacol Date: 2013-03-25 Impact factor: 5.176
Authors: Patricia G da Motta; Ana Paula C Veiga; Janetti N Francischi; Maria Aparecida K F Tatsuo Journal: Eur J Pharmacol Date: 2004-01-12 Impact factor: 4.432