Red nucleus IL-6 mediates the maintenance of neuropathic pain by inducing the productions of TNF-α and IL-1β through the JAK2/STAT3 and ERK signaling pathways.
|
| Abstract |
We previously reported that interleukin (IL)-6 in the red nucleus (RN) is involved in the maintenance of neuropathic pain induced by spared nerve injury (SNI), and exerts a facilitatory effect via Janus-activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) and extracellular signal-regulated kinase (ERK) signal transduction pathways. The present study aimed at investigating the roles of tumor necrosis factor-α (TNF-α) and IL-1β in RN IL-6-mediated maintenance of neuropathic pain and related signal transduction pathways. Being similar to the elevation of RN IL-6 three weeks after SNI, increased protein levels of both TNF-α and IL-1β were also observed in the contralateral RN three weeks after the nerve injury. The upregulations of TNF-α and IL-1β were closely correlative with IL-6 and suppressed by intrarubral injection of a neutralizing antibody against IL-6. Administration of either the JAK2 antagonist AG490 or the ERK antagonist PD98059 to the RN of rats with SNI remarkably increased the paw withdrawal threshold (PWT) and inhibited the up-regulations of local TNF-α and IL-1β. Further experiments indicated that intrarubral injection of exogenous IL-6 in naive rats apparently lowered the PWT of the contralateral hindpaw and boosted the local expressions of TNF-α and IL-1β. Pretreatment with AG490 could block IL-6-induced tactile hypersensitivity and suppress the up-regulations of both TNF-α and IL-1β. However, injection of PD98059 in advance only inhibited the upregulation of IL-1β, but not TNF-α. These findings indicate that RN IL-6 mediates the maintenance of neuropathic pain by inducing the productions of TNF-α and IL-1β. IL-6 induces the expression of TNF-α through the JAK2/STAT3 pathway, and the production of IL-1β through the JAK2/STAT3 and ERK pathways.
|
|---|---|
| Authors | Qing-Qing Yang, Hao-Nan Li, Shu-Ting Zhang, Yan-Li Yu, Wei Wei, Xi Zhang, Jun-Yang Wang, Xiao-Yan Zeng |
| Journal | Neuropathology : official journal of the Japanese Society of Neuropathology (Neuropathology) Vol. 40 Issue 4 Pg. 347-357 (Aug 2020) ISSN: 1440-1789 [Electronic] Australia |
| PMID | 32380573 (Publication Type: Journal Article) |
| Copyright | © 2020 Japanese Society of Neuropathology. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!