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Titolo: Neurochemical characterization Of Bortezomib-Induced peripheral neuropathy: Expression Of Trpv1, CGRP and Substance P in the rat DRG and spinal cord
Data di pubblicazione: 2012
Abstract: Bortezomib (BTZ), a selective ubiquitin-proteasome system inhibitor, is a potent antineoplastic drug to treat multiple myeloma. In clinical practice, a significant peripheral sensory neuropathy (PN), generally associated with impairment of Aß, Ad, and C type primary afferent fibers, represent the most significant side effect of its administration. However, the mechanism underlying its harmful effects remains still to be fully clarified. In order to investigate the possible neurochemical changes involved in neuropathic pain development, we used a well-established rat model of BTZ-induced PN, whose hallmarks are allodynia, neurophysiological and morphological alterations of myelinated and unmyelinated fibers of sciatic nerve. With this aim, by means of western blot (WB) and immunohistochemistry, we examined rat L4-L5 dorsal root ganglia (DRG) and spinal cord for their expression of the transient receptor potential vanilloid type-1 (TRPV1) and the sensory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP). In fact, TRPV1 is expressed by sensory neurons where it functions as a molecular integrator for nociception by causing release of CGRP and SP which, in turn, enhance the sensitization of nociceptors. WB showed that TRPV1 increased significantly in both DRG and spinal cord homogenates of BTZ-treated rats. In tissue sections, the proportion of DRG neurons expressing TRPV1 and CGRP was higher, though not significantly, in BTZ-treated than in control animals, whereas SP neurons did not change. Morphometry showed that labelled neurons fell predominantly in the class of small- and medium-sized cells. In the spinal cord an increase of TRPV1-, CGRP-LI nerve fibers and terminals occurred in the Lissauer's tract and superficial layers of the dorsal horn of BTZ-treated compared to controls. These observations will be useful to deeply understand the pathophysiology of the BTZ-induced neuropathic pain and allow potential more targeted therapies.
Tipologia:4.2 Abstract in Atti di convegno

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