Lin Y W, Tseng T J, Lin W M, Hsieh S T
Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, 10018, Taiwan.
Exp Neurol. 2001 Aug;170(2):290-6. doi: 10.1006/exnr.2001.7704.
Nociceptive nerves innervate the skin and play an important role in the generation of neuropathic pain. However, it remains elusive whether and how nociceptive nerve terminals degenerate in neuropathic pain conditions. To address this issue, we investigated cutaneous innervation in a model of painful mononeuropathy, the chronic constriction injury (CCI). The hind paws of rats were immunocytochemically stained with a pan-axonal marker, protein gene product 9.5 (PGP 9.5). Within 2 days after CCI, rats exhibited thermal hyperalgesia, and there was a partial depletion of epidermal nerves. The extent of reduction in epidermal nerves after CCI was variable with an epidermal nerve density of 3.65 +/- 1.97 fibers/mm (compared to 15.39 +/- 1.58 fibers/mm on the control side, P < 0.02). There was a mild but concomitant increase in PGP 9.5 (+) Langerhans cells in the epidermis of the skin with CCI (10.19 +/- 1.99 vs 7.75 +/- 1.36 cells/mm, P < 0.05). In the skin denervated by tight ligation of the sciatic nerve, epidermal nerves were completely depleted (0 fibers/mm vs. 12.26 +/- 1.44 fibers/mm on the control side, P < 0.001). Animals with tight ligation of the sciatic nerve exhibited thermal anesthesia. These findings suggest that the epidermis is partially denervated in CCI, and that a partial injury of nerves is correlated with the development of neuropathic pain.
伤害性神经支配皮肤，并在神经性疼痛的产生中起重要作用。然而，在神经性疼痛情况下伤害性神经末梢是否以及如何退化仍不清楚。为了解决这个问题，我们在一种疼痛性单神经病变模型——慢性压迫损伤（CCI）中研究了皮肤神经支配情况。用一种泛轴突标记物蛋白基因产物9.5（PGP 9.5）对大鼠后爪进行免疫细胞化学染色。CCI后2天内，大鼠出现热痛觉过敏，表皮神经部分缺失。CCI后表皮神经减少的程度各不相同，表皮神经密度为3.65±1.97条纤维/mm（对照侧为15.39±1.58条纤维/mm，P<0.02）。CCI皮肤表皮中PGP 9.5（+）朗格汉斯细胞有轻度但伴随性的增加（10.19±1.99对7.75±1.36个细胞/mm，P<0.05）。在坐骨神经紧密结扎去神经支配的皮肤中，表皮神经完全缺失（0条纤维/mm对对照侧的12.26±1.44条纤维/mm，P<0.001）。坐骨神经紧密结扎的动物表现出热麻醉。这些发现表明，在CCI中表皮部分去神经支配，并且神经的部分损伤与神经性疼痛的发展相关。
