Gabapentin Increases Intra-Epidermal and Peptidergic Nerve Fibers Density and Alleviates Allodynia and Thermal Hyperalgesia in a Mouse Model of Acute Taxol-Induced Peripheral Neuropathy

Abstract

The clinical pathology of Taxol-induced peripheral neuropathy (TIPN), characterized by loss of sensory sensitivity and pain, is mirrored in a preclinical pharmacological mice model in which Gabapentin, produced anti-thermal hyperalgesia and anti-allodynia effects. The study aimed to investigate the hypothesis that gabapentin may protect against Taxol-induced neuropathic pain in association with an effect on intra-epidermal nerve fibers density in the TIPN mice model. A TIPN study schedule was induced in mice by daily injection of Taxol during the first week of the experiment. Gabapentin therapy was performed during the 2nd and 3rd weeks. The neuropathic pain was evaluated during the whole experiment by the Von Frey, tail flick, and hot plate tests. Intra-epidermal nerve fibers (IENF) density in skin biopsies was measured at the end of the experiment by immunohistochemistry of ubiquitin carboxyl-terminal hydrolase PGP9.5 pan-neuronal and calcitonin gene-related (CGRP) peptides-I/II- peptidergic markers. Taxol-induced neuropathy was expressed by 80% and 73% reduction in the paw density of IENFs and CGPR, and gabapentin treatment corrected by 83% and 46% this reduction, respectively. Gabapentin-induced increase in the IENF and CGRP nerve fibers density, thus proposing these evaluations as an additional objective end-point tool in TIPN model studies using gabapentin as a reference compound.