Hsieh Yu-Lin, Chiang Hao, Tseng To-Jung, Hsieh Sung-Tsang
Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan.
J Neuropathol Exp Neurol. 2008 Feb;67(2):93-104. doi: 10.1097/nen.0b013e3181630bb8.
To generate an experimental neuropathy model in which small-diameter sensory nerves are specifically affected and to test a potential treatment, adult mice were given a single injection (50 microg/kg, i.p.) of the capsaicin analog resiniferatoxin (RTX). On Day 7 after RTX treatment, there was a 53% reduction in unmyelinated nerve density in the medial plantar nerve (p = 0.0067) and a 66% reduction in epidermal nerve density of hind paw skin (p = 0.0004) compared with vehicle-treated controls. Substance P-immunoreactive dorsal root ganglion neurons were also markedly depleted (p = 0.0001). These effects were associated with the functional deficit of prolonged withdrawal latencies to heat stimuli (p = 0.0007) on a hot plate test. The potential therapeutic effects of 4-methylcatechol (4MC) on this neuropathy were then tested by daily injections of 4MC (10 microg/kg, i.p.) from Days 7 to 35 after neuropathy induction. On Day 35, 4MC-treated mice had an increase in unmyelinated (p = 0.014) and epidermal nerve (p = 0.0013) densities and a reduction in thermal withdrawal latency (p = 0.0091) compared with RTX-only controls. These results indicate that 4MC promoted regeneration of unmyelinated nerves in experimental RTX-induced neuropathy and enhanced function.
为了建立一种小直径感觉神经受到特异性影响的实验性神经病变模型并测试一种潜在的治疗方法，给成年小鼠腹腔注射一次辣椒素类似物树脂毒素（RTX，50微克/千克）。在RTX治疗后第7天，与接受赋形剂处理的对照组相比，内侧足底神经中无髓神经密度降低了53%（p = 0.0067），后爪皮肤的表皮神经密度降低了66%（p = 0.0004）。P物质免疫反应性背根神经节神经元也明显减少（p = 0.0001）。这些效应与热板试验中对热刺激的撤腿潜伏期延长的功能缺陷相关（p = 0.0007）。然后通过在神经病变诱导后第7天至第35天每天腹腔注射4 - 甲基儿茶酚（4MC，10微克/千克）来测试4MC对这种神经病变的潜在治疗效果。在第35天，与仅接受RTX处理的对照组相比，接受4MC处理的小鼠无髓神经（p = 0.014）和表皮神经（p = 0.0013）密度增加，热撤腿潜伏期缩短（p = 0.0091）。这些结果表明，4MC促进了实验性RTX诱导的神经病变中无髓神经的再生并增强了功能。
