Tanaka M, Cummins T R, Ishikawa K, Dib-Hajj S D, Black J A, Waxman S G
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Neuroreport. 1998 Apr 20;9(6):967-72. doi: 10.1097/00001756-199804200-00003.
It has been suggested that hyperexcitability in dorsal root ganglion (DRG) neurons due to altered sodium channel expression contributes to some chronic pain syndromes. To understand the role of the voltage-gated sodium channel alpha-SNS in inflammatory pain, we investigated the expression of alpha-SNS mRNA and tetrodotoxin-resistant (TTX-R) sodium current in small DRG neurons, which include nociceptive cells, following injection of carrageenan into the hind paw of the rat using in situ hybridization and patch-clamp recording. alpha-SNS mRNA expression in DRG neurons projecting to the inflamed limb was significantly increased 4 days following carrageenan injection, compared with DRG neurons from the contralateral side or naive (uninjected) rats (mean +/- s.d. optical density ratio: ipsilateral/contralateral, 1.77 +/- 0.17; ipsilateral/naive, 1.88 +/- 0.36). The amplitude of the TTX-R sodium current in small DRG neurons projecting to the inflamed limb was significantly larger than on the contralateral side 4 days post-injection (31.7 +/- 3.3 vs 20.0 +/- 2.1 nA). The TTX-R current density was also significantly increased. These results demonstrate the increased expression of alpha-SNS sodium channels in small DRG neurons following injection of carrageenan into their projection field, and suggest that alpha-SNS is involved in the development of hyperexcitability associated with inflammation.
有人提出,由于钠通道表达改变导致的背根神经节(DRG)神经元兴奋性过高与某些慢性疼痛综合征有关。为了了解电压门控钠通道α-SNS在炎性疼痛中的作用,我们使用原位杂交和膜片钳记录技术,研究了在向大鼠后爪注射角叉菜胶后,包括伤害性感受细胞在内的小DRG神经元中α-SNS mRNA的表达和河豚毒素抗性(TTX-R)钠电流。与对侧或未注射(未处理)大鼠的DRG神经元相比,向发炎肢体投射的DRG神经元中α-SNS mRNA表达在注射角叉菜胶4天后显著增加(平均±标准差光密度比:同侧/对侧,1.77±0.17;同侧/未处理,1.88±0.36)。注射后4天,向发炎肢体投射的小DRG神经元中TTX-R钠电流的幅度显著大于对侧(31.7±3.3对20.0±2.1 nA)。TTX-R电流密度也显著增加。这些结果表明,在向小DRG神经元的投射区域注射角叉菜胶后,α-SNS钠通道的表达增加,提示α-SNS参与了与炎症相关的兴奋性过高的发展。