Intrathecal injection of spironolactone attenuates radicular pain by inhibition of spinal microglia activation in a rat model.
Intrathecal injection of spironolactone attenuates radicular pain by inhibition of spinal microglia activation in a rat model.
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DOI：
10.1371/journal.pone.0039897
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gu X
中科院分区：
文献类型：
--
作者：
Sun YE;Peng L;Sun X;Bo J;Yang D;Zheng Y;Liu C;Zhu B;Ma Z;Gu X
小胶质细胞可能通过神经炎性反应在伤害性加工和痛敏反应中发挥重要作用。小胶质细胞上表达的盐皮质激素受体(MR)可能在小胶质细胞活性调节中起中心作用。然而，小胶质细胞和MR在神经根性疼痛中的作用尚不清楚。本研究旨在探讨选择性MR拮抗剂螺内酯是否通过抑制脊髓小胶质细胞激活引起的神经炎症而发挥抗痛觉作用。用SURGIFLO™慢性压迫背根神经节产生神经根性疼痛。小胶质细胞、白介素β(IL-1β)、白介素6(IL-6)、肿瘤坏死因子-α(TN-α)、NMDA型受体的NR1亚单位(t-NR1s)和磷酸化的NR1型(p-NR1型)的表达也明显上调。鞘内注射螺内酯可明显减轻疼痛行为及小胶质细胞、IL-1β、肿瘤坏死因子-α、t-硝基转移酶和p-硝基转移酶的表达，但对IL-6的产生无明显影响。提示鞘内注射螺内酯对大鼠神经根性疼痛有一定的治疗作用。减少脊髓背角和背根神经节中神经胶质细胞的激活，减少促炎细胞因子的产生，下调NMDA受体的表达和磷酸化是其有益作用的主要机制。
Microglia might play an important role in nociceptive processing and hyperalgesia by neuroinflammatory process. Mineralocorticoid receptor (MR) expressed on microglia might play a central role in the modulation of microglia activity. However the roles of microglia and MR in radicular pain were not well understood. This study sought to investigate whether selective MR antagonist spironolactone develop antinociceptive effects on radicular pain by inhibition neuroinflammation induced by spinal microglia activation. Radicular pain was produced by chronic compression of the dorsal root ganglia with SURGIFLO™. The expression of microglia, interleukin beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), NR1 subunit of the NMDA receptor (t-NR1), and NR1 subunit phosphorylated at Ser896 (p-NR1) were also markedly up-regulated. Intrathecal injection of spironolactone significantly attenuated pain behaviors as well as the expression of microglia, IL-1β, TNF-α, t-NR1, and p-NR1, whereas the production of IL-6 wasn’t affected. These results suggest that intrathecal delivery spironolactone has therapeutic effects on radicular pain in rats. Decreasing the activation of glial cells, the production of proinflammatory cytokines and down-regulating the expression and phosphorylation of NMDA receptors in the spinal dorsal horn and dorsal root ganglia are the main mechanisms contributing to its beneficial effects.
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