Neuroimaging uncovers neuronal and metabolic changes in pain modulatory brain areas in a rat model of chemotherapy-induced neuropathy - MEMRI and ex vivo spectroscopy studies.

Autor: Costa-Pereira JT; Department of Biomedicine, Unit of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; IBMC-Institute of Molecular and Cell Biology, University of Porto, Portugal; I3S, Institute of Investigation and Innovation in Health, University of Porto, Portugal; Faculty of Nutrition and Food Sciences, University of Porto, Portugal., Oliveira R; Department of Biomedicine, Unit of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; IBMC-Institute of Molecular and Cell Biology, University of Porto, Portugal; I3S, Institute of Investigation and Innovation in Health, University of Porto, Portugal., Guadilla I; Instituto de Investigaciones Biomédicas 'Alberto Sols', CSIC-UAM, Arturo Duperier 4, 28029 Madrid, Spain., Guillén MJ; Instituto de Investigaciones Biomédicas 'Alberto Sols', CSIC-UAM, Arturo Duperier 4, 28029 Madrid, Spain., Tavares I; Department of Biomedicine, Unit of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; IBMC-Institute of Molecular and Cell Biology, University of Porto, Portugal; I3S, Institute of Investigation and Innovation in Health, University of Porto, Portugal., López-Larrubia P; Instituto de Investigaciones Biomédicas 'Alberto Sols', CSIC-UAM, Arturo Duperier 4, 28029 Madrid, Spain. Electronic address: plopez@iib.uam.es.
Jazyk: angličtina
Zdroj: Brain research bulletin [Brain Res Bull] 2023 Jan; Vol. 192, pp. 12-20. Date of Electronic Publication: 2022 Oct 31.
DOI: 10.1016/j.brainresbull.2022.10.018
Abstrakt: Chemotherapy-induced neuropathy (CIN) is one of the most common complications of cancer treatment with sensory dysfunctions which frequently include pain. The mechanisms underlying pain during CIN are starting to be uncovered. Neuroimaging allows the identification of brain circuitry involved in pain processing and modulation and has recently been used to unravel the disruptions of that circuitry by neuropathic pain. The present study evaluates the effects of paclitaxel, a cytostatic drug frequently used in cancer treatment, at the neuronal function in the anterior cingulate cortex (ACC), hypothalamus and periaqueductal gray (PAG) using manganese-enhanced magnetic resonance imaging (MEMRI). We also studied the metabolic profile at the prefrontal cortex (PFC) and hypothalamus using ex vivo spectroscopy. Wistar male rats were intraperitoneal injected with paclitaxel or vehicle solution (DMSO). The evaluation of mechanical sensitivity using von Frey test at baseline (BL), 21 (T21), 28 (T28), 49 (T49) and 56 days (T56) after CIN induction showed that paclitaxel-injected rats presented mechanical hypersensitivity from T21 until T56 after CIN induction. The evaluation of the locomotor activity and exploratory behaviors using open-field test at T28 and T56 after the first injection of paclitaxel revealed that paclitaxel-injected rats walked higher distance with higher velocity at late point of CIN accompanied with a sustained exhibition of anxiety-like behaviors. Imaging studies performed using MEMRI at T28 and T56 showed that paclitaxel treatment increased the neuronal activation in the hypothalamus and PAG at T56 in comparison with the control group. The analysis of data from ex vivo spectroscopy demonstrated that at T28 paclitaxel-injected rats presented an increase of N-acetyl aspartate (NAA) levels in the PFC and an increase of NAA and decrease of lactate (Lac) concentration in the hypothalamus compared to the control group. Furthermore, at T56 the paclitaxel-injected rats presented lower NAA and higher taurine (Tau) levels in the PFC. Together, MEMRI and metabolomic data indicate that CIN is associated with neuroplastic changes in brain areas involved in pain modulation and suggests that other events involving glial cells may be happening.
Competing Interests: Conflict of interest The authors have no conflicts of interest to declare.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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