疼痛是机体感受伤害性刺激时产生的一种神经感觉。位于感觉神经元上的疼痛相关受体，已经成为疼痛研究的焦点。 P2X3受体是表达在感觉神经元上的一类感知疼痛刺激的离子通道。我们研究发现蛋白酶激活受体（PAR-2）与P2X3受体在DRG神经元大量共表达，PAR-2受体被激活后通过细胞内磷酸激酶C（PKC）和A（PKA）以协同的方式增强P2X3受体的活性。我们的研究还显示，这种增强效应并不是通过磷酸化P2X3通道，而是通过增加其在细胞膜的表达来实现的。因此在炎症时，PAR-2受体被激活后可以通过增强P2X3受体活性而导致疼痛的发生和发展。 1999年报道的TRPA1也是一种在感觉神经元上表达的参与痛觉信号调节和传导的离子通道。它不仅参与炎性痛的产生及发展，对神经损伤时产生的疼痛也有重要的调节作用。我们的研究发现，一种COX2的抑制剂，etodolac，在高浓度时可以直接兴奋TRPA1通道，而在临床口服剂量后出现的血药浓度范围内虽然对TRPA1不能引起明显的兴奋作用，但是却明显抑制了TRPA1的活性。这项研究揭示了etodolac除了对炎症性疼痛的缓解作用外，可能还通过激活及使TRPA1通道脱敏感而抑制神经损伤时产生的疼痛反应。 这些疼痛相关受体的研究为我们了解疼痛的发生发展和寻找缓解疼痛的方法提供了理论依据。

Pain is an unpleasant feeling that often caused by nociceptive stimulus in sensory system. The more and more studies focus on the nociceptors in sensory neurons in pain research. P2X3 is mainly localized on nociceptors. We found that the protease activated receptor (PAR-2) and P2X3 receptor in neurons of the co expression of DRG. PAR-2 activation increased the P2X3 activation through protein kinase C (PKC) or protein kinase A (PKA) pathways in a synergetic manner. Moreover, PAR-2 agonists may potentiate the P2X3 ion channel, and the mechanism of this potentiation is likely to be a result of translocation, but not phosphorylation of the receptor. These results demonstrate a functional interaction of the protease signal with the ATP signal, and a novel mechanism through which protease released in response to tissue inflammation might trigger the sensation to pain through P2X3 activation. It is reported that TRPA1 is an ion channel which involved in pain modulation and conduction. TRPA1 is involved in inflammatory pain, as well as the modulation of neuropathic pain. In our study, etodolac, a COX2 inhibitor, can directly activate TRPA1 channel at higher concentration. Application of etodolac at drug plasma levels in clinical usage did not induce significant TRPA1 currents, but reduced the subsequent TRPA1 activation. These data indicate a novel mechanism of the anti-inflammatory and analgesic clinical effects of etodolac, which may be involved with its direct activation and the subsequent desensitization of TRPA1 and to relieveneuropathic pain. These studies contribute us to understand the pain and find out the ways to relieve pain.