Role of Dopaminergic Receptors Within the Ventral Tegmental Area in Antinociception Induced by Chemical Stimulation of the Lateral Hypothalamus in an Animal Model of Orofacial Pain

Abstract

Tina Matini,1 Amir Haghparast,1 Laleh Rezaee,2 Sakineh Salehi,2,3 Azita Tehranchi,4 Abbas Haghparast2 1School of Dentistry, International Branch of Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Department of Medicine, Ardabil Medical Sciences Branch, Islamic Azad University, Ardabil, Iran; 4Dental Research Center, Research Institute of Dental Sciences, Dental School, Shahid Beheshti University of Medical Sciences, Tehran, IranCorrespondence: Abbas HaghparastNeuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, P O Box 19615-1178, Tehran, IranTel/ Fax [phone]Email [email protected] TehranchiDental Deformities Research Center, Dental Research Institute, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, IranEmail [email protected]: The ventral tegmental area (VTA), as one of the classical components of the brain reward circuitry, shares large neural networks with the pain processing system. We previously showed the role of VTA dopamine receptors in modulation of lateral hypothalamus (LH)-induced antinociception in acute pain conditions. However, considering the fact that the neural systems involved in the mediation of tonic pain are not the same as those that mediate phasic pain. In the present study, we aimed to examine the role of intra-VTA dopamine receptors in LH-induced antinociceptive responses during tonic orofacial pain conditions.Methods: Male Wistar rats weighing 230– 250 g were implanted with two separate cannulae into the LH and VTA on the same side. Different solutions of carbachol (62.5, 125 and 250 nM), as a non-selective cholinergic receptor agonist that activates the LH projecting neurons, were microinjected into the LH. In the other groups, D1-like dopamine receptor antagonist, SCH-23390 (0.25, 1 and 4 μg/03 μL saline) or D2-like dopamine receptor antagonist, Sulpiride (0.25, 1 and 4 μg/0.3 μL DMSO 12%) were microinjected into VTA, 5 min prior intra-LH carbachol (250 nM), then subjected to orofacial formalin test. Intra-LH carbachol microinjection dose-dependently attenuated biphasic orofacial pain.Results: Intra-VTA administration of SCH-23390 or Sulpiride dose-dependently decreased intra-LH carbachol-induced antinociception during both phases of orofacial formalin test with further effects in the late phase.Discussion: The findings suggest that chemical stimulation of the LH by carbachol possibly activates the orexin projecting neurons and subsequently, the VTA dopaminergic neurons involved in the orofacial pain modulation. Detecting such neural circuitry offers an alternative approach in the development of more efficient therapies for such debilitating pain conditions.Keywords: pain, D1-like dopamine receptor, D2-like dopamine receptor, ventral tegmental area, lateral hypothalamus, orofacial formalin test

Keywords

• pain
• d1-like dopamine receptor
• d2-like dopamine receptor
• ventral tegmental area
• lateral hypothalamus
• orofacial formalin test