Spinal cord stimulation prevents paclitaxel-induced mechanical and cold hypersensitivity and modulates spinal gene expression in rats.

Chemotherapy-induced peripheral neuropathy Neuropathic pain RNA-sequencing Rat Spinal cord stimulation

Journal

Pain reports
ISSN: 2471-2531
Titre abrégé: Pain Rep
Pays: United States
ID NLM: 101683899

Informations de publication

Date de publication:
Historique:
received: 25 04 2019
revised: 06 08 2019
accepted: 10 08 2019
entrez: 26 12 2019
pubmed: 26 12 2019
medline: 26 12 2019
Statut: epublish

Résumé

Paclitaxel-induced peripheral neuropathy (PIPN) is a common dose-limiting side effect of this cancer treatment drug. Spinal cord stimulation (SCS) has demonstrated efficacy for attenuating some neuropathic pain conditions. We aim to examine the inhibitory effect of SCS on the development of PIPN pain and changes of gene expression in the spinal cord in male rats after SCS. We examined whether traditional SCS (50 Hz, 6-8 h/session daily for 14 consecutive days) administered during paclitaxel treatment (1.5 mg/kg, i.p.) attenuates PIPN-related pain behavior. After SCS treatment, we performed RNA-seq of the lumbar spinal cord to examine which genes are differentially expressed after PIPN with and without SCS. Compared to rats treated with paclitaxel alone (n = 7) or sham SCS (n = 6), SCS treatment (n = 11) significantly inhibited the development of paclitaxel-induced mechanical and cold hypersensitivity, without altering open-field exploratory behavior. RNA-seq showed that SCS induced upregulation of 836 genes and downregulation of 230 genes in the spinal cord of paclitaxel-treated rats (n = 3) as compared to sham SCS (n = 5). Spinal cord stimulation upregulated immune responses in paclitaxel-treated rats, including transcription of astrocyte- and microglial-related genes, but repressed transcription of multiple gene networks associated with synapse transmission, neuron projection development, γ-aminobutyric acid reuptake, and neuronal plasticity. Our findings suggest that traditional SCS may attenuate the development of pain-related behaviors in PIPN rats, possibly by causing aggregate inhibition of synaptic plasticity through upregulation and downregulation of gene networks in the spinal cord.

Identifiants

pubmed: 31875188
doi: 10.1097/PR9.0000000000000785
pii: PAINREPORTS-D-19-0076
pmc: PMC6882571
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e785

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS070814
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS110598
Pays : United States

Informations de copyright

Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.

Déclaration de conflit d'intérêts

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

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Auteurs

Eellan Sivanesan (E)

Department of Anesthesiology and Critical Care Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA.

Kimberly E Stephens (KE)

Department of Anesthesiology and Critical Care Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA.
Department of Pharmacology and Molecular Sciences, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA.
Center for Epigenetics, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA.

Qian Huang (Q)

Department of Anesthesiology and Critical Care Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA.

Zhiyong Chen (Z)

Department of Anesthesiology and Critical Care Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA.

Neil C Ford (NC)

Department of Anesthesiology and Critical Care Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA.

Wanru Duan (W)

Department of Anesthesiology and Critical Care Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA.

Shao-Qui He (SQ)

Department of Anesthesiology and Critical Care Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA.

Xinyan Gao (X)

Department of Anesthesiology and Critical Care Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA.

Bengt Linderoth (B)

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Srinivasa N Raja (SN)

Department of Anesthesiology and Critical Care Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA.

Yun Guan (Y)

Department of Anesthesiology and Critical Care Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA.
Department of Neurological Surgery, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

Classifications MeSH