慢性压迫性神经损伤大鼠中透明质酸合成变化及其在神经源性疼痛中的作用

Regulation of hyaluronic acid synthesis and the role in neuropathic pain following chronic constriction injury in rats

慢性神经源性疼痛由于其发病机制尚不完全明确,目前还没有十分有效的治疗手段;神经损伤后炎症反应和免疫调节机制在疼痛的发生中发挥着重要作用,透明质酸(HA)近来被认为是炎症和免疫调节中一个重要的调节分子。为了进一步研究HA是否参与到神经损伤后的病理过程中,我们检测了慢性压迫性神经损伤(CC I)大鼠损伤神经的HA含量。结果显示:与正常神经比较,HA的含量在损伤后7 d明显增加,HA合成酶(HAS)的表达也明显上调。4-甲基伞形酮(4-MU)是HAS的一种抑制剂,我们通过给予4-MU抑制HA的合成,研究HA在慢性神经源性疼痛中的作用,发现给药组CC I大鼠损伤足对热痛刺激的敏感性低于未给药组,同时IL-1β的表达量低于未给药组。以上结果提示HA可能通过对炎症因子的调控参与到损伤后的疼痛机制中,这一结果将有助于慢性神经源性疼痛的治疗。

The mechanisms of neuropathie pain are still unclear and there is no effective therapy method at present. Inflammatory response and immune regulation are important in the development of neuropathic pain after nerve injury. It has been reported that hyaluronie acid （HA） is an important factor in inflammation and immune regulation. In order to find out whether HA is also involved in nerve injury we detected the HA content of injured nerve after chronic constriction injury （CCI）. The results showed that HA significantly increased in CCI rats 7 d after injury compared with normal and hyaluronan synthases （HAS） were also upregulated. A hyaluronan synthases inhibitor, 4- methylunbelliferone （4-MU） was used to inhibit HA synthesis in our study. We found that CCI rats with 4-MU administered exhibited reduced HA synthesis and thermal hyperalgesia compared with CCI rats without 4-MU treatment. That IL-113 expressional decrease was also found in CCI rats with 4-MU treatment compared with CCI rats that were not given 4-MU 7 d after injury. These results indicate that HA might play an important role in neuropathic pain by modulating inflammatory factors after nerve injury and were useful for the treatment of neuropathic pain.