Interleukin-17 regulates neuron-glial communications, inhibitory synaptic transmission and neuropathic pain after chemotherapy
The proinflammatory cytokine Interleukin-17 (IL-17) is produced mainly by Th17 cells and has been implicated in pain regulation. However, synaptic mechanisms by which IL-17 regulates pain transmission are unknown. Here we report that glia-produced IL-17 suppresses inhibitory synaptic transmission in spinal cord pain circuit and drives chemotherapy-induced neuropathic pain. We observed respective expression of IL-17 and its receptor IL-17R in spinal cord astrocytes and neurons. Patch clamp recording in spinal cord slices revealed that IL-17 not only enhanced EPSCs but also suppressed IPSCs and GABA-induced currents in lamina IIo somatostatin-expressing neurons. Spinal IL-17 was upregulated after paclitaxel treatment, and intrathecal IL-17R blockade reduced paclitaxel-induced neuropathic pain. In dorsal root ganglia, respective IL-17 and IL-17R expression in satellite glial cells and neurons was sufficient and required for inducing neuronal hyperexcitability after paclitaxel. Together, our data show that IL-17/IL-17R mediate both central and peripheral neuron-glial interactions in chemotherapy-induced peripheral neuropathy.
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