Laboratory of Pain Research, Institute of Physiology, Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic.
Int J Mol Sci. 2021 Jan 20;22(3):991. doi: 10.3390/ijms22030991.
The mechanisms of inflammatory pain need to be identified in order to find new superior treatments. Protease-activated receptors 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) are highly co-expressed in dorsal root ganglion neurons and implicated in pain development. Here, we examined the role of spinal PAR2 in hyperalgesia and the modulation of synaptic transmission in carrageenan-induced peripheral inflammation, using intrathecal (i.t.) treatment in the behavioral experiments and recordings of spontaneous, miniature and dorsal root stimulation-evoked excitatory postsynaptic currents (sEPSCs, mEPSCs and eEPSCs) in spinal cord slices. Intrathecal PAR2-activating peptide (AP) administration aggravated the carrageenan-induced thermal hyperalgesia, and this was prevented by a TRPV1 antagonist (SB 366791) and staurosporine i.t. pretreatment. Additionally, the frequency of the mEPSC and sEPSC and the amplitude of the eEPSC recorded from the superficial dorsal horn neurons were enhanced after acute PAR2 AP application, while prevented with SB 366791 or staurosporine pretreatment. PAR2 antagonist application reduced the thermal hyperalgesia and decreased the frequency of mEPSC and sEPSC and the amplitude of eEPSC. Our findings highlight the contribution of spinal PAR2 activation to carrageenan-induced hyperalgesia and the importance of dorsal horn PAR2 and TRPV1 receptor interactions in the modulation of nociceptive synaptic transmission.
为了找到新的更优疗法，需要确定炎症性疼痛的机制。蛋白酶激活受体 2（PAR2）和瞬时受体电位香草酸 1 型（TRPV1）在背根神经节神经元中高度共表达，并与疼痛发展有关。在这里，我们通过鞘内（i.t.）给药在行为实验中研究了脊髓 PAR2 在神经病理性疼痛中的作用，以及在角叉菜胶诱导的外周炎症中对突触传递的调制作用，并在脊髓切片中记录自发性、微小和背根刺激诱发的兴奋性突触后电流（sEPSC、mEPSC 和 eEPSC）。鞘内 PAR2 激活肽（AP）给药加重了角叉菜胶引起的热痛觉过敏，这可以被 TRPV1 拮抗剂（SB 366791）和 staurosporine i.t.预处理所预防。此外，急性 PAR2 AP 给药后，从浅层背角神经元记录到的 mEPSC 和 sEPSC 的频率以及 eEPSC 的振幅增加，而 SB 366791 或 staurosporine 预处理则可预防这种情况。PAR2 拮抗剂的应用降低了热痛觉过敏，并降低了 mEPSC 和 sEPSC 的频率以及 eEPSC 的振幅。我们的研究结果强调了脊髓 PAR2 激活对角叉菜胶诱导的痛觉过敏的贡献，以及背角 PAR2 和 TRPV1 受体相互作用在调节伤害性突触传递中的重要性。
