Interleukin-10 down-regulates voltage gated sodium channels in rat dorsal root ganglion neurons.
The over-expression of voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons following peripheral nerve injury contributes to neuropathic pain by generation of the ectopic discharges of action potentials. However, mechanisms underlying the change in VGSCs' expression are poorly understood. Our previous work has demonstrated that the pro-inflammatory cytokine TNF-α up-regulates VGSCs. In the present work we tested if anti-inflammatory cytokine IL-10, which had been proven to be effective for treating neuropathic pain, had the opposite effect. Western blot and immunofluorescence results showed that IL-10 receptor was localized in DRG neurons. Recombinant rat IL-10 (200 pg/ml) not only reduced the densities of TTX-sensitive and Nav1.8 currents in control DRG neurons, but also reversed the increase of the sodium currents induced by rat recombinant TNF-α (100 pg/ml), as revealed by patch-clamp recordings. Consistent with the electrophysiological results, real-time PCR and western blot revealed that IL-10 (200 pg/ml) down-regulated VGSCs in both mRNA and protein levels and reversed the up-regulation of VGSCs by TNF-α. Moreover, repetitive intrathecal administration of rrIL-10 for 3 days (4 times per day) attenuated mechanical allodynia in L5 spinal nerve ligation model and profoundly inhibited the excitability of DRG neurons. These results suggested that the down-regulation of the sodium channels in DRG neurons might contribute to the therapeutic effect of IL-10 on neuropathic pain.
Pain Research Center and Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, China.
Kai-Feng
KF
Shen
He-Quan
HQ
Zhu
Xu-Hong
XH
Wei
Jun
J
Wang
Yong-Yong
YY
Li
Rui-Ping
RP
Pang
Xian-Guo
XG
Liu
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D005727:Ganglia, Spinal / Q000473:pathology*; D016753:Interleukin-10 / Q000494:pharmacology*; D008026:Ligation; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053701:Receptors, Interleukin-10 / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000235:genetics / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D053701:Receptors, Interleukin-10; D026941:Sodium Channel Blockers; D014409:Tumor Necrosis Factor-alpha; D061566:Voltage-Gated Sodium Channels; D016753:Interleukin-10; D013779:Tetrodotoxin
Dorsal root ganglion neurons; Interleukin-10; Neuropathic pain; TNF-α; Voltage-gated sodium channels