MrgC受体独特性地分布在感觉神经节小细胞神经元中，属G蛋白偶联受体；其激活能抑制吗啡镇痛作用耐受。过去的研究和预实验提示，这一作用可能与MrgC受体抑制脊髓胶质细胞的活动有关。本项目拟研究MrgC受体对脊髓背角和背根神经节(DRG)中胶质细胞的作用。目的在于：探讨MrgC受体是否参与吗啡耐受的发生；MrgC受体如何调控慢性应用吗啡引起的胶质细胞激活；验证假说，即MrgC受体抑制DRG神经元兴奋性递质和调质的合成和释放，从而调控神经元和脊髓小胶质细胞、和DRG卫星细胞(属胶质细胞)之间的cross-talk。本项目主要研究MrgC受体抑制吗啡耐受的神经生物学机制，也将涉及对吗啡耐受形成机理的探讨。MrgC受体的分布具高度特异性，如以其为靶点，产生的副作用会很小或没有。故本研究结果还可能为MrgC受体作为临床上治疗吗啡耐受的药物靶点奠定理论基础。

Mas-related gene C receptors (MrgC) are uniquely distributed in the small-sized neurons of trigeminal and dorsal root ganglia and belong to G protein-coupled receptors. It has been demonstrated that the activation of MrgC receptors can inhibit tolerance to morphine-induced analgesia. Our pilot experiment shows that the effect of MrgC receptors on morphine tolerance may be ascribed to the inhibition of glial activation in the spinal cord. This application proposes to study the effects of MrgC receptors on glial cells in the spinal dorsal horn and dorsal root ganglia. The study aims to investigate the possible involvement of MrgC receptors in the development of morphine tolerance and it's modulation on the chronic morphine-induced glial activation. We will examine the hypothesis that MrgC receptors can inhibit the synthesis and release of the excitatory neurotransmitter and neuromodulator in the DRG neurons, preventing cross-talk between DRG neurons and spinal microglia or DRG satellite cells. This study will explore neurobiological mechanisms of modulation of morphine tolerance by MrgC receptors and the principle of the development of morphine tolerance as well. As MrgC receptors are highly restricted in pain-related neurons in sensory ganglia, targeting these receptors will not impact other physiological functions. Hence, the present study will also provide evidence to support that MrgC receptors can be considered as a therapeutic target of relieving morphine tolerance in clinic.