Spinal cord stimulation prevents paclitaxel-induced mechanical and cold hypersensitivity and modulates spinal gene expression in rats
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | PAIN Reports, Vol 4, Iss 5, p e785 (2019) |
| Druh dokumentu: | article |
| ISSN: | 2471-2531 00000000 |
| DOI: | 10.1097/PR9.0000000000000785 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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