title: Intraepidermal nerve fiber loss corresponds to the development of taxol-induced hyperalgesia and can be prevented by treatment with minocycline.
abstract: 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 2mg/kg of Taxol every other day for four injections (day 1, 3, 5, and 7). Minocycline (25mg/kg) was given in a separate group of rats 24h prior to the first dose of Taxol and every day for the next 9days (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.
authors.affiliation: Department of Anesthesiology and Pain Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Boyette-Davis
authors.forename: W
authors.initials: W
authors.lastname: Xin
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: P M
authors.initials: PM
authors.lastname: Dougherty
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004817:Epidermis / Q000187:drug effects / Q000294:innervation* / Q000473:pathology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D017239:Paclitaxel / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009498:Neurotoxins; D008911:Minocycline; D017239:Paclitaxel