Deuis Jennifer R, Yin Kathleen, Cooper Matthew A, Schroder Kate, Vetter Irina
IMB Centre for Pain Research, Institute for Molecular Bioscience, The University of Queensland, 306 Carmody Rd. (Building 80), St Lucia, Queensland 4072, Australia.
IMB Centre for Inflammation and Disease Research, Institute for Molecular Bioscience, The University of Queensland, 306 Carmody Rd. (Building 80), St Lucia, Queensland 4072, Australia.
Burns. 2017 Mar;43(2):304-309. doi: 10.1016/j.burns.2016.09.001. Epub 2016 Dec 28.
The NLRP3 inflammasome is a multi-protein complex that assembles in response to tissue damage or infection, triggering activation of caspase-1, an enzyme that converts interleukin (IL)-1β into its active form. A role for the NLRP3 inflammasome is emerging in inflammatory pain, but its influence in other pain types is largely unexamined. Therefore the aim of this study was to assess the role of the NLRP3 inflammasome and its downstream product caspase-1 in a model of acute burn-induced pain in male mice. A superficial burn was induced on the plantar surface of the left hind paw using a hot plate set at 52.5°C for 25s. Development of burn-induced mechanical allodynia, thermal allodynia, edema and weight bearing changes was assessed in Nlrp3 and caspase-1-deficient (Ice) mice, and in mice administered the selective NLRP3 inflammasome inhibitor MCC950. Burn-induced mechanical and thermal allodynia developed normally in Nlrp3 and Ice mice and mice administered MCC950. Burn-induced edema was significantly reduced in Ice mice only. Burn-induced weight bearing changes were attenuated in Nlrp3 mice and mice administered MCC950 72h after burn only. This study suggests that NLRP3 and its downstream product caspase-1 have a limited role in the development of burn-induced pain.
NLRP3炎性小体是一种多蛋白复合物，在组织损伤或感染时组装，触发半胱天冬酶-1的激活，半胱天冬酶-1是一种将白细胞介素（IL）-1β转化为其活性形式的酶。NLRP3炎性小体在炎性疼痛中的作用正在显现，但其在其他疼痛类型中的影响在很大程度上尚未得到研究。因此，本研究的目的是评估NLRP3炎性小体及其下游产物半胱天冬酶-1在雄性小鼠急性烧伤诱导疼痛模型中的作用。使用设置为52.5°C的热板在左后爪足底表面诱导浅度烧伤25秒。在Nlrp3和半胱天冬酶-1缺陷（Ice）小鼠以及给予选择性NLRP3炎性小体抑制剂MCC950的小鼠中评估烧伤诱导的机械性异常性疼痛、热异常性疼痛、水肿和负重变化。烧伤诱导的机械性和热异常性疼痛在Nlrp3和Ice小鼠以及给予MCC950的小鼠中正常发展。仅在Ice小鼠中，烧伤诱导的水肿明显减轻。仅在烧伤后72小时，Nlrp3小鼠和给予MCC950的小鼠中，烧伤诱导的负重变化减弱。本研究表明，NLRP3及其下游产物半胱天冬酶-1在烧伤诱导疼痛的发展中作用有限。
