Role of Spinal Cord alpha(2)-Adrenoreceptors in Noradrenergic Inhibition of Nociceptive Transmission During Chemotherapy-Induced Peripheral Neuropathy

• Tipo: Artigo em Revista Científica Internacional
• Data: 2020

Autores

Costa Pereira, JT (Autor) FCNAUP; Ribeiro, J (Autor) Outra; Maria Isabel Martins (Autor) FMUP; Isaura Tavares (Autor) FMUP

Revista

Título: Frontiers in Neuroscience

Vol. 13

ISSN: 1662-4548

Editora: Frontiers Media

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 19 Citações

Outras Informações

ID Authenticus: P-00R-PAD

DOI: 10.3389/fnins.2019.01413

Abstract (EN): Chemotherapy-induced peripheral neuropathy (CIPN) is a problem during cancer treatment and for cancer survivors but the central mechanisms underlying CIPN remain understudied. This study aims to determine if CIPN is associated with alterations of noradrenergic modulation of nociceptive transmission at the spinal cord. CIPN was induced in male Wistar rats by paclitaxel injections. One month after CIPN induction, the behavioral effects of the administration of reboxetine (noradrenaline reuptake inhibitor), clonidine (agonist of alpha(2)-adrenoreceptors; alpha(2)(-)AR) and atipamezole (antagonist of alpha(2)(-)AR) were evaluated using the von Frey and cold plate tests. Furthermore, we measured the expression of the noradrenaline biosynthetic enzyme dopamine-beta-hydroxylase (DBH) and of alpha(2)(-)AR in the spinal dorsal horn. Reboxetine and clonidine reversed the behavioral signs of CIPN whereas the opposite occurred with atipamezole. In the 3 pharmacological approaches, a higher effect was detected in mechanical allodynia, the pain modality which is under descending noradrenergic control. DBH expression was increased at the spinal dorsal horn of paclitaxel-injected animals. The enhanced noradrenergic inhibition during CIPN may represent an adaptation of the descending noradrenergic pain control system to the increased arrival of peripheral nociceptive input. A potentiation of the alpha(2)(-)AR mediated antinociception at the spinal cord may represent a therapeutic opportunity to face CIPN.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12