我们在临床工作中注意到大量黄疸患者同时存在痛觉抑制与瘙痒增加现象，明确疼痛与瘙痒在外周神经产生过程中的相互作用对有效控制恶性疼痛或瘙痒至关重要。TRPV1及TRPA1受体均可介导痛觉，又都参与瘙痒发生，我们前期研究发现，黄疸时的主要可能致痒分子溶血磷脂酸(LPA)预处理，能够显著抑制V1受体介导的痛觉，增加A1受体相关的痒觉，且后者依赖于前者作用。据此，我们针对黄疸时伤害性感觉功能异常的具体机制提出: 黄疸时升高的LPA可抑制TRPV1相关痛觉，V1功能抑制可间接增强A1功能，易化与A1相关的痒觉，而该过程主要在V1/A1双阳性神经元上完成，连接两个受体的Tmem100蛋白及胞内的钙离子应该具体介导了双阳性神经元在伤害性感觉编码中的关键作用及两个受体间的相互影响。本课题为明确黄疸时伤害性感觉病理改变的机制以及外周编码痛痒感觉的具体过程提供实验支持，以求未来更精确特异地抑制伤害性感觉的发生。

During our clinical work, we noticed that there was both pain suppression and itch facilitation in many cholestatic patients, and it’s essential to know the peripheral interaction between pain and itch during their initiation to control the pathological pain or itch, so we propose that the peripheral pathological change in these patients should give us important implication for understanding the nerve coding process of pain and itch. It is well known that both TRPV1 and TRPA1 are involved in pain and itch transmission, and our preliminary results indicate that when pretreated with lysophosphatidic acid (LPA), the main potential pruritogen for cholestatic itch, the TRPV1 receptor mediated pain sensation can be suppressed obviously, while the itch response related to TRPA1 receptor will be increased significantly, and the potentiation of TRPA1 related itch is dependent of suppression of TRPV1. So, according to what is mentioned above, our hypothesis is that the elevated LPA in cholestatic condition can suppress V1 related pain, and the A1 mediated itch response will be increased through TRPV1 suppression, this process mainly happens in the TRPV1/A1 double positive DRG neurons, which should play an important role during the peripheral pain and itch modulation. The Tmem100 protein which connect the two receptors inside the neurons and intracellular calcium may be involved in determining the specific role of double positive DRG neurons in pain and itch generation, also the interaction between these two receptors. By this study, we want to make it clear that how LPA induce cholestatic itch, and provide more experimental supports for the mechanisms of peripheral noxious sensation interaction, and hopefully we can control the initiation of pain or itch more previously and effectively in the near future based on the study.