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MRNA expression of spinal dorsal horn in oxaliplatin-treated rats

ABSTRACT: Oxaliplatin-induced neuropathic pain is a common dose-limiting side effect of cancer treatment but the underlying mechanisms are largely unknown. The neuropathic pain model was established by oxaliplatin intraperitoneal administration for five consecutive days. In the present study, we performed whole genome expression microarray analysis by using spinal dorsal horn from oxaliplatin-treated and vehicle-treated rats on day 10.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE146739 | GEO | 2020/03/11

REPOSITORIES: GEO

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Project description:Background: The pathogenesis of neuropathic pain and the reasons for the prolonged unhealing are still unknown. Increasing evidence suggests that oestrogen sex differences play a role in pain sensitivity, but few studies focused on the role of oestrogen receptor which maybe an important molecular component contributing to peripheral pain transduction. We aimed to investigate the impact of ooestrogen receptors in nociceptive neuronal response in the dorsal root ganglion (DRG) and spinal dorsal horn using a spared nerve injury (SNI) rat model of chronic pain. Methods: We used a class of oestrogen receptors antagonists and agonists intrathecal (i.t.) administrated to male rats with SNI or normal rats to identify the main receptor. Moreover, we applied genes identified through genomic metabolic analysis to determine the key metabolism point and elucidate potential mechanisms mediating continuous neuronal sensitisation and neuroinflammation responses in neuropathic pain. The excitability of DRG neurons was detected using the patch clamp technique. Primary culture was used to extract microglia and DRG neurons, and siRNA transfection was used to silence receptor protein expression. Immunofluorescence, Western blotting, qPCR and behavioral testing were used to assess the expressions, cellular distributions, and actions of main receptor and its related signaling molecules. Results: Increasing the expression and function of G protein-coupled oestrogen receptor (GPER), but not oestrogen receptor-α (ERα) and oestrogen receptor-β (ERβ), in the DRG neuron and microglia, but not the dorsal spinal cord, contributed to SNI-induced neuronal sensitisation. Inhibiting GPER expression in the DRG alleviated SNI-induced pain behaviours and neuroinflammation by downregulating iNOS, IL-1β and IL-6 expression as well as restoring GABAα2 expression simultaneously. Additionally, the positive interaction between GPER and β-alanine, β-alanine accumulation enhances pain sensation and promotes chronic pain development. Conclusion: GPER activation in the DRG causes a positive interaction of β-alanine with iNOS, IL-1β and IL-6 expression and represses GABAα2 involved in post-SNI neuropathic pain development. Blocking GPER and eliminating β-alanine in the DRG neuron and microglia may prevent neuropathic pain development.

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MRNA expression of spinal dorsal horn in oxaliplatin-treated rats

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