TY - JOUR
T1 - Intraepidermal nerve fiber loss corresponds to the development of Taxol-induced hyperalgesia and can be prevented by treatment with minocycline
AU - Boyette-Davis, J.
AU - Xin, W.
AU - Zhang, H.
AU - Dougherty, P. M.
N1 - Funding Information:
This work was supported by National Institute of Health grant NS46606 and National Cancer Institute grant CA124787 and by the Astra-Zeneca Corporation .
PY - 2011/2
Y1 - 2011/2
N2 - 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. The progression of Taxol-induced mechanical hypersensitivity coincides with loss of intraepidermal nerve fibers, and the hyperalgesia and nerve fiber loss were prevented with minocycline treatment.
AB - 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. The progression of Taxol-induced mechanical hypersensitivity coincides with loss of intraepidermal nerve fibers, and the hyperalgesia and nerve fiber loss were prevented with minocycline treatment.
KW - Chemotherapy
KW - Intraepidermal nerve fibers
KW - Minocycline
KW - Neuropathy
KW - Skin biopsy
KW - Taxol
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U2 - 10.1016/j.pain.2010.10.030
DO - 10.1016/j.pain.2010.10.030
M3 - Article
C2 - 21145656
AN - SCOPUS:78651477418
SN - 0304-3959
VL - 152
SP - 308
EP - 313
JO - Pain
JF - Pain
IS - 2
ER -