Khasar S G, Gold M S, Levine J D
Department of Anatomy, Medicine and Oral Maxillofacial Surgery, Graduate Program in Neuroscience, NIH Pain Center (UCSF), University of California, San Francisco 94143-0440, USA.
Neurosci Lett. 1998 Oct 30;256(1):17-20. doi: 10.1016/s0304-3940(98)00738-1.
We report evidence for a contribution of tetrodotoxin-resistant sodium current (TTX-R INa) to prostaglandin E2 (PGE2)-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 INa (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 PGE2-induced hyperalgesia. PGE2-induced hyperalgesia returned to normal 7 days after the last injection of antisense ODN. Antisense ODN selectively and significantly reduced TTX-R INa current density in cultured sensory neurons. Our observations support the hypothesis that modulation of TTX-R INa, present in peripheral terminals of primary afferent nociceptors, contributes, at least in part, to inflammatory hyperalgesia. Since TTX-R INa is found only in primary afferent nociceptors, our findings suggest TTX-R INa as a promising target for novel therapeutic interventions for the treatment of inflammatory pain.
我们报告了河豚毒素抗性钠电流（TTX-R INa）对前列腺素E2（PGE2）诱导的痛觉过敏有作用的证据。在长期植入脊髓套管的大鼠中进行行为实验。该研究采用鞘内注射针对最近克隆的TTX-R INa（PN3/SNS）基础通道的反义寡脱氧核苷酸（ODN）。采用伤害性屈曲反射来确定机械刺激诱导的爪部退缩阈值的变化。注射反义ODN而非正义或错配ODN导致PGE2诱导的痛觉过敏减轻。在最后一次注射反义ODN 7天后，PGE2诱导的痛觉过敏恢复正常。反义ODN选择性且显著降低了培养的感觉神经元中的TTX-R INa电流密度。我们的观察结果支持这样的假设，即初级传入伤害感受器外周终末中存在的TTX-R INa的调节至少部分地导致炎症性痛觉过敏。由于TTX-R INa仅在初级传入伤害感受器中发现，我们的研究结果表明TTX-R INa是治疗炎症性疼痛的新型治疗干预的一个有前景的靶点。
