Neurochemical characterization of primary sensory neurons in a rat model of bortezomic-induced peripheral neuropathy
type: CreativeWork
description: Peripheral neuropathies, as the result of nerve damage, are characterized by pain, numbness, and tingling in the extremities and slow nerve conduction. Chemotherapy-induced peripheral neuropathy is a major dose-limiting side effect of many other commonly used chemotherapeutic agents, including platinum drugs, taxanes, epothilones and vinca alkaloids, but also newer agents such as bortezomib. Bortezomib (VELCADE) is a boronic acid dipeptide, which causes a selective blockade of proteasome activity. Bortezomib-induced peripheral neuropathy is an important clinical complication, often difficult to manage or reverse, whose treatment usually involves dose reduction, interruption, or cessation of therapy. Though many animal models of chemotherapy-induced peripheral neuropathy have been designed, knowledge concerning the mechanisms that may underlie neurochemical changes accompanying the onset of bortezomib-induced peripheral neuropathy is still poor. In this study, to analyze the possible neurochemical changes occurring in primary sensory neurons, the effects of a single-dose intravenous administration and a well-established “chronic” schedule (three times/week for 8 weeks) in a rat model of bortezomib-induced peripheral neuropathy have been examined. The transient.receptor.potential.vanilloid.type.1 (TRPV1) channel and sensory neuropeptides calcitonin.gene-related.peptide (CGRP) and substance.P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal cord and sciatic nerve using western blot (WB), immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR). Behavioral measures, performed at the end of the chronic bortezomib-treatment, confirmed a reduction of the mechanical nociceptive threshold, whereas no difference occurred in the thermal withdrawal latency. In the DRGs, TRPV1-, CGRP- and SP-immunoreactive neurons were mostly small- and medium-sized and the proportion of TRPV1- and CGRP-labeled neurons increased after treatment. A bortezomi…
abstract: Peripheral neuropathies, as the result of nerve damage, are characterized by pain, numbness, and tingling in the extremities and slow nerve conduction. Chemotherapy-induced peripheral neuropathy is a major dose-limiting side effect of many other commonly used chemotherapeutic agents, including platinum drugs, taxanes, epothilones and vinca alkaloids, but also newer agents such as bortezomib. Bortezomib (VELCADE) is a boronic acid dipeptide, which causes a selective blockade of proteasome activity. Bortezomib-induced peripheral neuropathy is an important clinical complication, often difficult to manage or reverse, whose treatment usually involves dose reduction, interruption, or cessation of therapy. Though many animal models of chemotherapy-induced peripheral neuropathy have been designed, knowledge concerning the mechanisms that may underlie neurochemical changes accompanying the onset of bortezomib-induced peripheral neuropathy is still poor. In this study, to analyze the possible neurochemical changes occurring in primary sensory neurons, the effects of a single-dose intravenous administration and a well-established “chronic” schedule (three times/week for 8 weeks) in a rat model of bortezomib-induced peripheral neuropathy have been examined. The transient.receptor.potential.vanilloid.type.1 (TRPV1) channel and sensory neuropeptides calcitonin.gene-related.peptide (CGRP) and substance.P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal cord and sciatic nerve using western blot (WB), immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR). Behavioral measures, performed at the end of the chronic bortezomib-treatment, confirmed a reduction of the mechanical nociceptive threshold, whereas no difference occurred in the thermal withdrawal latency. In the DRGs, TRPV1-, CGRP- and SP-immunoreactive neurons were mostly small- and medium-sized and the proportion of TRPV1- and CGRP-labeled neurons increased after treatment. A bortezomi…
author: PODDIGHE, LAURA
language: eng
keywords: DRG, Gangli spinali, RT-PCR, chemotherapy-induced, immunohistochemistry, midollo spinale, neuropatia periferica indotta da chemioterapici, spinal cord, western blot, Settore BIO/16 - Anatomia Umana
date published: 2014-03-31
date modified: 2026-07-24T01:30:01Z
provider: Università di Cagliari
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Cagliari

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11584/266419