GSE132491
Spinal cord stimulation prevents paclitaxel-induced mechanical and cold hypersensitivity and modulates spinal gene expression in rats
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 for the development of PIPN pain in rats. Methods: We examined whether traditional SCS administered during paclitaxel treatment  attenuates PIPN-related pain behavior. After SCS, we carried out 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). SCS upregulated immune responses in paclitaxel-treated rats, including transcription of astrocyte- and microglial-related genes, but repressed transcription of multiple gene networks associated with synaptic plasticity, neuron projection development, g-aminobutyric acid reuptake, and long-term potentiation. Conclusion: Our findings suggest that traditional SCS may attenuate the development of pain-related behaviors in PIPN, partially by causing aggregate inhibition of synaptic plasticity through up- and down-regulation of gene networks in the spinal cord. Overall design: RNAseq of 3 study groups: Naïve rats, rats after paclitaxel and SCS electrode placement (sham control), rats after paclitaxel, SCS electrode placement and SCS