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Papers of the Week

Papers: 16 Nov 2019 - 22 Nov 2019

Animal Studies

2019 Nov 19

Cell Rep



Interleukin-17 Regulates Neuron-Glial Communications, Synaptic Transmission, and Neuropathic Pain after Chemotherapy.


Luo H, Liu H-Z, Zhang W-W, Matsuda M, Lv N, Chen G, Xu Z-Z, Zhang Y-Q
Cell Rep. 2019 Nov 19; 29(8):2384-2397.e5.
PMID: 31747607.


The proinflammatory cytokine interleukin-17 (IL-17) is implicated in pain regulation. However, the synaptic mechanisms by which IL-17 regulates pain transmission are unknown. Here, we report that glia-produced IL-17 suppresses inhibitory synaptic transmission in the spinal cord pain circuit and drives chemotherapy-induced neuropathic pain. We find that IL-17 not only enhances excitatory postsynaptic currents (EPSCs) but also suppresses inhibitory postsynaptic synaptic currents (IPSCs) and GABA-induced currents in lamina II somatostatin-expressing neurons in mouse spinal cord slices. IL-17 mainly expresses in spinal cord astrocytes, and its receptor IL-17R is detected in somatostatin-expressing neurons. Selective knockdown of IL-17R in spinal somatostatin-expressing interneurons reduces paclitaxel-induced hypersensitivity. Overexpression of IL-17 in spinal astrocytes is sufficient to induce mechanical allodynia in naive animals. In dorsal root ganglia, IL-17R expression in nociceptive sensory neurons is sufficient and required for inducing neuronal hyperexcitability after paclitaxel. Together, our data show that IL-17/IL-17R mediate neuron-glial interactions and neuronal hyperexcitability in chemotherapy-induced peripheral neuropathy.