Intraepidermal nerve fiber loss corresponds to the development of Taxol-induced hyperalgesia and can be prevented by treatment with minocycline

被引:177
作者
Boyette-Davis, J. [1 ]
Xin, W. [2 ,3 ]
Zhang, H. [1 ]
Dougherty, P. M. [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Pain Med, Houston, TX 77030 USA
[2] Sun Yat Sen Univ, Zhongshan Med Sch, Dept Physiol, Guangzhou 510275, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Zhongshan Med Sch, Pain Res Ctr, Guangzhou 510275, Guangdong, Peoples R China
关键词
Intraepidermal nerve fibers; Taxol; Neuropathy; Minocycline; Skin biopsy; Chemotherapy; PAINFUL PERIPHERAL NEUROPATHY; TUMOR-NECROSIS-FACTOR; INDUCED MECHANICAL ALLODYNIA; ACETYL-L-CARNITINE; POSTHERPETIC NEURALGIA; LANGERHANS CELLS; FACTOR-ALPHA; PACLITAXEL; RAT; VINCRISTINE;
D O I
10.1016/j.pain.2010.10.030
中图分类号
R614 [麻醉学];
学科分类号
100217 [麻醉学];
摘要
Loss of intraepidermal nerve fibers (IENFs) has been speculated to play a critical role in the development of various neuropathies. In this study, the density of IENFs were studied over time during the induction of Taxol (Bristol-Myers Squibb, NY, USA)-induced chemoneuropathy and compared with the changes in IENFs in animals co-treated with Taxol plus the protective agent minocycline. Rats were injected (intraperitoneally) with 2 mg/kg of Taxol every other day for four injections (day 1, 3, 5, and 7). Minocycline (25 mg/kg) was given in a separate group of rats 24 h prior to the first dose of Taxol and every day for the next 9 days (day 0 through 9). Animals were tested for mechanical paw withdrawal thresholds prior to any drug administrations and again on day 7, 14, and 30. Immunohistochemistry using the pan-neuronal marker protein gene product 9.5 was performed on glabrous skin of the hind-paw foot pad to stain for IENFs also on day 7, 14, and 30. The results show that Taxol-treated animals developed mechanical sensitivity and corresponding IENF loss. Animals receiving minocycline plus Taxol showed no hyperalgesia or loss of IENFs. This study confirms, for the first time, that a loss of IENFs occurs as a neuropathy develops, and further shows a protection against both IENF loss and hyperalgesia with minocycline treatment. (C) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:308 / 313
页数:6
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