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

Eellan Sivanesan, Kimberly E. Stephens, Qian Huang, Zhiyong Chen, Neil C. Ford, Wanru Duan, Shao Qui He, Xinyan Gao, Bengt Linderoth, Srinivasa N. Raja, Yun Guan

Research output: Contribution to journalArticle

Abstract

Introduction: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.Objective: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.Methods: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.Results: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.Conclusion: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.

Original languageEnglish (US)
Article numbere785
JournalPain Reports
Volume4
Issue number5
DOIs
StatePublished - Sep 1 2019

Keywords

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

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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