Ulinastatin attenuates neuropathic pain induced by L5-VRT via the calcineurin/IL-10 pathway.
Ulinastatin attenuates neuropathic pain induced by L5-VRT via the calcineurin/IL-10 pathway.
复制标题
乌司他丁通过钙调神经磷酸酶/IL-10 途径减轻 L5-VRT 引起的神经性疼痛
DOI：
10.1177/1744806916646785
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发表时间：
2016
期刊：
影响因子：
3.3
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Ouyang H;Nie B;Wang P;Li Q;Huang W;Xin W;Zeng W;Liu X
先前的研究表明，乌司他丁是一种有效的炎症反应抑制剂，在临床应用中可以减轻啮齿动物的痛敏反应。然而，潜在的机制仍不清楚。在本研究中，我们首先检测了大鼠腰5腹根切断后钙调神经磷酸酶水平的变化，钙调神经磷酸酶在调节神经系统细胞因子释放方面起着重要作用。此外，我们还测定了腹膜腔内(I.P.)注射乌司他丁通过抑制钙调神经磷酸酶介导的炎症反应减轻腰5腹根切断引起的疼痛行为。结果表明，与假手术组相比，腰5腹根切断组大鼠的缩足阈值和缩足潜伏期明显缩短。腰5腹根切断引起的神经病理性疼痛使背根神经节内钙调神经磷酸酶的表达显著减少，钙调神经磷酸酶主要定位于NF-200阳性细胞、IB4阳性细胞和CGRP阳性细胞，少量定位于GFAP阳性卫星细胞。鞘内(I.T.)注射外源性钙调神经磷酸酶可减轻腰5腹根切断所致的疼痛行为。重要的是，腹腔注射乌司他丁可减轻腰5腹根切断引起的疼痛行为和钙调神经磷酸酶下调。最后，腰5腹根切断后细胞因子IL-10显著降低，鞘内应用钙调神经磷酸酶或乌司他丁可抑制腰5腹根切断后IL-10的下调。这些结果提示，乌司他丁通过作用于CN/IL-10通路，可能成为治疗神经病理性疼痛的有效新药。
Previous studies have shown that ulinastatin, an effective inhibitor of the inflammatory response in clinical applications, can attenuate hyperalgesia in rodents. However, the underlying mechanism remains unclear. In the present study, we first examined the change in the calcineurin level, which plays an important role in regulating cytokine release in the nervous system, following lumbar 5 ventral root transection in the rat. Furthermore, we determined whether intraperitoneal (i.p.) injection of ulinastatin attenuated pain behavior via inhibition of the calcineurin-mediated inflammatory response induced by lumbar 5 ventral root transection. The results showed that the paw withdrawal threshold and paw withdrawal latency were significantly decreased following lumbar 5 ventral root transection compared to the sham group. Neuropathic pain induced by lumbar 5 ventral root transection significantly decreased the expression of calcineurin in the DRG, and calcineurin was mostly located with NF-200-positive cells, IB4-positive cells, and CGRP-positive cells and less with GFAP-positive satellite cells. Furthermore, intrathecal (i.t.) injection of exogenous calcineurin attenuated the pain behavior induced by lumbar 5 ventral root transection. Importantly, intraperitoneal injection of ulinastatin alleviated the pain behavior and calcineurin downregulation induced by lumbar 5 ventral root transection. Lastly, the cytokine IL-10 was significantly decreased following lumbar 5 ventral root transection, and application of calcineurin (intrathecal) or ulinastatin (intraperitoneal) inhibited the IL-10 downregulation induced by lumbar 5 ventral root transection. These results suggested that ulinastatin, by acting on the CN/IL-10 pathway, might be a novel and effective drug for the treatment of neuropathic pain.