Dulu Thomas D, Kanui Titus I, Towett Philemon K, Maloiy Geoffrey M, Abelson Klas S P
Associate Professor, University of Copenhagen, Department of Experimental Medicine, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark.
In Vivo. 2014 Jan-Feb;28(1):39-48.
The naked mole-rat (Heterocephalus glaber) is a promising animal model for the study of pain mechanisms, therefore a thorough characterization of this species is essential. The aim of the present study was to establish the naked mole-rat as a model for studying the cholinergic receptor system in antinociception by investigating the involvement of muscarinic, nicotinic and opioid receptors in nociceptive tests in this species. The effects of systemic administration of the muscarinic receptor agonist oxotremorine and the nicotinic receptor agonist epibatidine were investigated in the tail-flick, the hot-plate, and the formalin tests. The effects of co-administration of the muscarinic receptor antagonist atropine, the nicotinic receptor antagonist mecamylamine, and the opioid receptor antagonist naloxone were also investigated. Oxotremorine and epibatidine induced a significant, dose-dependent antinociceptive effect in the tail-flick, hot-plate, and formalin tests, respectively. The effects of oxotremorine and epibatidine were blocked by atropine and mecamylamine, respectively. In all three nociceptive tests, naloxone in combination with oxotremorine or epibatidine enhanced the antinociceptive effects of the drugs. The present study demonstrated that stimulation of muscarinic and nicotinic receptors produces antinociceptive effects in the naked-mole rat. The reversal effect of atropine and mecamylamine suggests that this effect is mediated by cholinergic receptors. As naloxone increases the antinociceptive effects of cholinergic agonists, it is suggested that the cholinergic antinociception acts via a gateway facilitated by opioid receptor blockage; however, the precise interaction between these receptor systems needs further investigation.
裸鼹鼠（Heterocephalus glaber）是研究疼痛机制的一种很有前景的动物模型，因此对该物种进行全面的特征描述至关重要。本研究的目的是通过研究毒蕈碱、烟碱和阿片受体在该物种伤害性感受测试中的作用，将裸鼹鼠确立为研究抗伤害感受中胆碱能受体系统的模型。在甩尾、热板和福尔马林测试中，研究了全身给予毒蕈碱受体激动剂氧化震颤素和烟碱受体激动剂埃博霉素的效果。还研究了联合给予毒蕈碱受体拮抗剂阿托品、烟碱受体拮抗剂美加明和阿片受体拮抗剂纳洛酮的效果。氧化震颤素和埃博霉素分别在甩尾、热板和福尔马林测试中诱导出显著的、剂量依赖性的抗伤害感受作用。氧化震颤素和埃博霉素的作用分别被阿托品和美加明阻断。在所有三项伤害性感受测试中，纳洛酮与氧化震颤素或埃博霉素联合使用增强了药物的抗伤害感受作用。本研究表明，刺激毒蕈碱和烟碱受体在裸鼹鼠中产生抗伤害感受作用。阿托品和美加明的逆转作用表明这种作用是由胆碱能受体介导的。由于纳洛酮增加了胆碱能激动剂的抗伤害感受作用，提示胆碱能抗伤害感受作用是通过阿片受体阻断促进的途径发挥作用；然而，这些受体系统之间的确切相互作用需要进一步研究。
