Bortezomib treatment produces nocifensive behavior and changes in the expression of TRPV1, CGRP, and substance P in the rat DRG, spinal cord, and sciatic nerve.
Bortezomib treatment produces nocifensive behavior and changes in the expression of TRPV1, CGRP, and substance P in the rat DRG, spinal cord, and sciatic nerve.
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DOI：
10.1155/2014/180428
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发表时间：
2014
影响因子：
--
通讯作者：
Marmiroli P
中科院分区：
文献类型：
--
作者：
Quartu M;Carozzi VA;Dorsey SG;Serra MP;Poddighe L;Picci C;Boi M;Melis T;Del Fiacco M;Meregalli C;Chiorazzi A;Renn CL;Cavaletti G;Marmiroli P
为了研究与硼替佐米诱导的疼痛性周围神经病变（PN）相关的神经化学变化，我们在硼替佐米诱导的PN大鼠模型中研究了单次静脉注射硼替佐米和完善的“慢性”给药方案的影响。本实验研究了大鼠L4-L5背根神经节、脊髓和坐骨神经TRPV 1通道和感觉神经肽CGRP和P物质（SP）的变化。在慢性硼替佐米治疗结束时进行的行为测量证实了机械伤害性阈值的降低，而热退缩潜伏期没有差异。Western blot分析显示，急性和慢性硼替佐米给药后，DRG和脊髓中TRPV 1相对增加。逆转录-聚合酶链反应显示慢性治疗后TRPV 1和CGRP mRNA相对水平下降。免疫组化结果显示，在DRG中，TRPV 1、CGRP和SP免疫反应阳性神经元多为中小型神经元，且TRPV 1和CGRP阳性神经元比例增加。还观察到硼替佐米诱导的背角TRPV 1和CGRP免疫反应性神经支配密度增加。我们的研究结果表明，硼替佐米治疗选择性地影响可能参与伤害性刺激处理的DRG神经元亚群，并且神经化学变化可能有助于硼替佐米诱导的PN疼痛的发展和持续。
To investigate neurochemical changes associated with bortezomib-induced painful peripheral neuropathy (PN), we examined the effects of a single-dose intravenous administration of bortezomib and a well-established “chronic” schedule in a rat model of bortezomib-induced PN. The TRPV1 channel and sensory neuropeptides CGRP and substance P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal cord, and sciatic nerve. Behavioral measures, performed at the end of the chronic bortezomib treatment, confirmed a reduction of mechanical nociceptive threshold, whereas no difference occurred in thermal withdrawal latency. Western blot analysis showed a relative increase of TRPV1 in DRG and spinal cord after both acute and chronic bortezomib administration. Reverse transcriptase-polymerase chain reaction revealed a decrease of TRPV1 and CGRP mRNA relative levels after chronic treatment. Immunohistochemistry showed that in the DRGs, TRPV1-, CGRP-, and SP-immunoreactive neurons were mostly small- and medium-sized and the proportion of TRPV1- and CGRP-labeled neurons increased after treatment. A bortezomib-induced increase in density of TRPV1- and CGRP-immunoreactive innervation in the dorsal horn was also observed. Our findings show that bortezomib-treatment selectively affects subsets of DRG neurons likely involved in the processing of nociceptive stimuli and that neurochemical changes may contribute to development and persistence of pain in bortezomib-induced PN.
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DOI：
10.1016/j.jpain.2011.04.008
发表时间：
2011-09
期刊：
The journal of pain
影响因子：
--
作者：
Boyette-Davis JA;Cata JP;Zhang H;Driver LC;Wendelschafer-Crabb G;Kennedy WR;Dougherty PM
通讯作者：
Dougherty PM
影响因子：
5.3
作者：
Cui, M.;Honore, P.;Faltynek, C. R.
通讯作者：
Faltynek, C. R.
影响因子：
2.4
作者：
Adams, J;Kauffman, M
通讯作者：
Kauffman, M
影响因子：
3.4
作者：
Guo, A;Vulchanova, L;Elde, R
通讯作者：
Elde, R
影响因子：
2.5
作者：
Chao, Tom;Pham, Khoa;Gupta, Ranjan
通讯作者：
Gupta, Ranjan