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A型肉毒杆菌毒素可降低佐剂性关节炎疼痛大鼠背根神经节中TRPV1的表达。

Botulinum toxin type A reduces TRPV1 expression in the dorsal root ganglion in rats with adjuvant-arthritis pain.

作者信息

Fan Chenglei, Chu Xiao, Wang Lin, Shi Hao, Li Tieshan

机构信息

Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, PR China.

Department of Pharmacy of Qingdao Municipal Hospital, Qingdao, Shandong Province, PR China.

出版信息

Toxicon. 2017 Jul;133:116-122. doi: 10.1016/j.toxicon.2017.05.001. Epub 2017 May 3.

Abstract

Arthritis pain affects people's long-term health, and recent studies have demonstrated that transient receptor potential vanilloid type 1 (TRPV1) plays a crucial role in arthritis pain. In addition, Pre-clinical evidence indicated that botulinum toxin type A (BoNT/A) has antinociceptive effect. The present study investigated the causality between the antinociceptive effects of BoNT/A and the expression of TRPV1 in dorsal root ganglion (DRG) in rats with adjuvant-arthritis pain. The results showed that BoNT/A significantly reduced adjuvant-arthritis nociceptive behaviors in a dose-dependent manner. Furthermore, the BoNT/A cleaved synaptosomal-associated protein of 25 kDa (cl-SNAP-25) was detected in the DRG using immunofluorescence after intra-articular administration. Although BoNT/A significantly reduced the protein levels of TRPV1, there were no significant changes in the mRNA levels of TRPV1 between CFA and BoNT/A (1U, 3U, 10U) group after BoNT/A retrograde axonal transport into the DRG with quantitative RT-PCR. This research provides evidence that the antinociceptive mechanism of BoNT/A might be mediated by reduction of TRPV1 expression through inhibition of its plasma membrane trafficking after intra-articular administration.

摘要

关节炎疼痛会影响人们的长期健康,最近的研究表明,瞬时受体电位香草酸亚型1(TRPV1)在关节炎疼痛中起关键作用。此外,临床前证据表明A型肉毒杆菌毒素(BoNT/A)具有抗伤害感受作用。本研究调查了BoNT/A的抗伤害感受作用与佐剂性关节炎疼痛大鼠背根神经节(DRG)中TRPV1表达之间的因果关系。结果表明,BoNT/A以剂量依赖的方式显著降低了佐剂性关节炎的伤害感受行为。此外,关节内给药后,使用免疫荧光法在DRG中检测到了BoNT/A切割的25 kDa突触体相关蛋白(cl-SNAP-25)。虽然BoNT/A显著降低了TRPV1的蛋白水平,但在BoNT/A经逆行轴突运输进入DRG后,通过定量逆转录聚合酶链反应检测发现,CFA组与BoNT/A(1U、3U、10U)组之间TRPV1的mRNA水平没有显著变化。本研究提供了证据,表明BoNT/A的抗伤害感受机制可能是通过关节内给药后抑制TRPV1的质膜运输,从而降低其表达来介导的。

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