Investigation of noradrenergic receptor system in anti-nociception using formalin test in the naked mole rat (Heterocephalus glaber)

The naked mole rat (NMR) is a rodent that has gained importance as a biomedical research model for various conditions like hypoxic brain injury, cancer and nociception. This study was designed to investigate possible involvement of the noadrenergic receptor system in antinoception in the NMR, using the alpha-2 adrenergic receptor specific ligands clonidine (agonist) and yohimbine (antagonist) in the formalin test. Formalin test followed 30 min after intraperitoneal administration of ligands or control. A total of 96 naked mole rats were used. A significant reduction in nociceptive behaviours was demonstrated after administration of clonidine in the doses 1,3,10 and 30 μg/kg (n = 8 per group). Doses of clonidine above 30 μg/kg caused loss of motor and proprietion skills exhibited by prostration and failure to turn over when placed on their backs. The antinociception by 3 μg/kg clonidine was reversed by administration of 30 μg/kg of yohimbine. The present study demonstrates that the noradrenergic receptor system is present and involved in formalin test-related antinociceptive mechanisms in the NMR, similar to other mammals. Given the increasing importance of the NMR as a model for pain and nociception, the species may prove useful as an animal model for noradrenergic mechanisms in pain modulation.