A tetrodotoxin-resistant sodium current mediates inflammatory pain in the rat
A tetrodotoxin-resistant sodium current mediates inflammatory pain in the rat
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DOI：
10.1016/s0304-3940(98)00738-1
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发表时间：
1998-10-30
影响因子：
2.5
通讯作者：
Levine, JD
中科院分区：
文献类型：
--
作者：
Khasar, SG;Gold, MS;Levine, JD
我们报告了河豚毒素抵抗钠电流（TTX-R I-Na）对前列腺素E-2（PGE（2））诱导的痛觉过敏的贡献的证据。在长期植入脊髓插管的大鼠中进行行为学实验。本研究采用鞘内给药寡脱氧核苷酸（ODN）反义最近克隆的通道TTX-R I-Na（PN 3/SNS）。采用伤害性屈曲反射测定机械刺激引起的缩爪阈值的变化。给予反义ODN而不是正义或错配ODN，导致PGE（2）诱导的痛觉过敏减少。PGE（2）诱导的痛觉过敏在最后一次注射反义ODN后7天恢复正常。反义ODN选择性地显著降低培养的感觉神经元TTX-R I-Na电流密度。我们的观察结果支持这一假设，TTX-R的I-Na，在初级传入伤害性感受器的外周末梢的调制，有助于，至少部分，炎性痛觉过敏。由于TTX-R I-Na仅在初级传入伤害感受器中发现，因此我们的研究结果表明TTX-R I-Na是治疗炎性疼痛的新型治疗干预的有希望的靶点。(C)1998爱思唯尔科学爱尔兰有限公司保留所有权利。
We report evidence for a contribution of tetrodotoxin-resistant sodium current (TTX-R I-Na) to prostaglandin E-2 (PGE(2))-induced hyperalgesia. Behavioral experiments were performed in rats chronically implanted with spinal cannulae. The study employed intrathecal administration of oligodeoxynucleotide (ODN) antisense to the recently cloned channel underlying TTX-R I-Na (PN3/SNS). The nociceptive flexion reflex was employed to determine changes in mechanical stimulus-induced paw-withdrawal threshold. Administration of antisense but not of sense or mismatch ODN, led to a decrease in PGE(2)-induced hyperalgesia. PGE(2)-induced hyperalgesia returned to normal 7 days after the last injection of antisense ODN. Antisense ODN selectively and significantly reduced TTX-R I-Na current density in cultured sensory neurons. Our observations support the hypothesis that modulation of TTX-R I-Na, present in peripheral terminals of primary afferent nociceptors, contributes, at least in part, to inflammatory hyperalgesia. Since TTX-R I-Na is found only in primary afferent nociceptors, our findings suggest TTX-R I-Na as a promising target for novel therapeutic interventions for the treatment of inflammatory pain. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.