Synthesis and analgesic effects of μ-TRTX-Hhn1b on models of inflammatory and neuropathic pain.
Synthesis and analgesic effects of μ-TRTX-Hhn1b on models of inflammatory and neuropathic pain.
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DOI：
10.3390/toxins6082363
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发表时间：
2014-08-13
期刊：
影响因子：
4.2
通讯作者：
Shi X
中科院分区：
文献类型：
--
作者：
Liu Y;Tang J;Zhang Y;Xun X;Tang D;Peng D;Yi J;Liu Z;Shi X
μ-TRTX-HHN1b(HNTX-IV)是从海纳鸟蛛毒液中分离得到的一种由35个氨基酸组成的多肽。它抑制电压门控钠通道Nav1.7，后者被认为是疼痛的治疗靶点。本研究的目的是阐明合成的μ-TRTX-HH1b对疼痛动物模型的镇痛作用。首先合成了该多肽，然后成功地复性/氧化。该合成肽对HEK 293细胞瞬时表达的人NA1.7电流具有与天然毒素相同的抑制作用。此外，在炎症性疼痛和神经病理性疼痛模型上考察了合成肽的镇痛作用。μ-TRTX-HH1b可有效逆转腹缩模型中的急性伤害性疼痛，并显著降低福尔马林模型40分钟内的疼痛评分。μ-TRTX-HH1b在两种模型上的作用与吗啡相当。在脊神经模型中，μ-TRTX-HH1b对痛觉异常的逆转作用比美西律更持久、更有效。这些结果表明，μ-TRTX-HH1b能有效地减轻动物的急性炎症性疼痛和慢性神经病理性疼痛，为进一步的临床止痛药物设计提供了一个有吸引力的模板。
μ-TRTX-Hhn1b (HNTX-IV) is a 35-amino acid peptide isolated from the venom of the spider, Ornithoctonus hainana. It inhibits voltage-gated sodium channel Nav1.7, which has been considered as a therapeutic target for pain. The goal of the present study is to elucidate the analgesic effects of synthetic μ-TRTX-Hhn1b on animal models of pain. The peptide was first synthesized and then successfully refolded/oxidized. The synthetic peptide had the same inhibitory effect on human Nav1.7 current transiently expressed in HEK 293 cells as the native toxin. Furthermore, the analgesic potentials of the synthetic peptide were examined on models of inflammatory pain and neuropathic pain. μ-TRTX-Hhn1b produced an efficient reversal of acute nociceptive pain in the abdominal constriction model, and significantly reduced the pain scores over the 40-min period in the formalin model. The efficiency of μ-TRTX-Hhn1b on both models was equivalent to that of morphine. In the spinal nerve model, the reversal effect of μ-TRTX-Hhn1b on allodynia was longer and higher than mexiletine. These results demonstrated that μ-TRTX-Hhn1b efficiently alleviated acute inflammatory pain and chronic neuropathic pain in animals and provided an attractive template for further clinical analgesic drug design.
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