Interleukin-17 Regulates Neuron-Glial Communications, Synaptic Transmission, and Neuropathic Pain after Chemotherapy.
Cell Rep
; 29(8): 2384-2397.e5, 2019 11 19.
Article
em En
| MEDLINE
| ID: mdl-31747607
ABSTRACT
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 IIo 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.
Palavras-chave
Cre-recombinase-dependent adeno-associated virus (AAV); allodynia; astrocytes; chemotherapy-induced peripheral neuropathy; excitatory postsynaptic currents (EPSCs); inhibitory postsynaptic synaptic currents (IPSCs); interleukin-17; neuron-glial interaction; somatostatin-expressing neurons; spinal cord
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transmissão Sináptica
/
Interleucina-17
/
Neuralgia
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China