Sensitization of voltage activated calcium channel currents for capsaicin in nociceptive neurons by tumor-necrosis-factor-α
Sensitization of voltage activated calcium channel currents for capsaicin in nociceptive neurons by tumor-necrosis-factor-α
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DOI：
10.1016/j.brainresbull.2009.09.012
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发表时间：
2010-01-15
影响因子：
3.8
通讯作者：
Buesselberg, D.
中科院分区：
文献类型：
--
作者：
Hagenacker, T.;Czeschik, J. C.;Buesselberg, D.
在神经病理性疼痛的大鼠模型中，肿瘤坏死因子-α(TNF-α)的应用使神经元钙通道对热刺激敏感。本研究探讨了肿瘤坏死因子-α(TNF-α)对辣椒素诱导的电压激活钙通道电流(I-Ca(V))的调节作用。TRPV-1受体受热激活，在神经病理性疼痛综合征的热痛敏发病机制中起重要作用，而电压激活的通道则是神经元信号传递所必需的。在大鼠背根神经节神经元上，通过去极化静息电位至0 mV，使I-Ca(V)降低16.9+/-2.2%。而辣椒素(0.1µM)使电流降低27+/-4.3%。预先给予肿瘤坏死因子-α(100 ng/ml)24小时，钙离子对辣椒素(0.1mU)有增敏作用，其作用受TRPV-1介导，下降42.8+/-4.4%。L型电流(36.6+/-5.2%)和P/Q型电流(35.6+/-4.1%)也可被激活，其中以N型电流最为敏感(74.5+/-7.3%)。当应用肿瘤坏死因子-α时，辣椒素引起的向超极化电压范围的移动不会发生。综上所述，肿瘤坏死因子-α使伤害性神经元对辣椒素敏感。(C)2009 Elsevier Inc.保留所有权利。
It is known that application of tumor-necrosis-factor-alpha (TNF-alpha) sensitizes neuronal calcium channels for heat stimuli in rat models of neuropathic pain. This study examines whether TNF-alpha modulates the capsaicin-induced effects after transient receptor potential vanilloid (TRPV)-1 receptor activation on voltage activated calcium channel currents (I-Ca(V)).TRPV-1 receptors are activated by heat and play an important role in the pathogenesis of thermal hyperalgesia in neuropathic pain syndromes, while voltage activated channels are essential for transmission of neuronal signals.Eliciting I-Ca(V) in DRG neurons of rats by a depolarization from the resting potential to 0 mV, TNF-alpha (100 ng/ml) reduces I-Ca(V) by 16.9 +/- 2.2%, while capsaicin (0.1 mu M) decreases currents by 27 +/- 4.3%. Pre-application of TNF-alpha (100 ng/ml) for 24 h results in a sensitization of I-Ca(V) to capsaicin (0.1 mu M) with a reduction of 42.8 +/- 4.4% mediated by TRPV-1. While L-type (36.6 +/- 5.2%) and P/Q type currents (35.6 +/- 4.1%) are also sensitized by TRPV-1 activation, N-type channel currents are most sensitive (74.5 +/- 7.3%). The capsaicin-induced shift towards the hyperpolarizing voltage range does not occur when TNF-alpha is applied. Summarizing, TNF-alpha sensitizes nociceptive neurons for capsaicin. (C) 2009 Elsevier Inc. All rights reserved.