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© 2022. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Our previous studies have clarified that red nucleus (RN) IL-6 is involved in the maintenance of neuropathic pain and produces facilitatory effect by activating JAK2/STAT3 and ERK pathways. Here, we further explored the immune molecular mechanisms of rubral IL-6-mediated descending facilitation at the spinal cord level. IL-6-evoked tactile allodynia was established by injecting recombinant IL-6 into the unilateral RN of naive male rats. Following intrarubral administration of IL-6, an obvious tactile allodynia was evoked in the contralateral hindpaw of rats. Meanwhile, the expressions of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 were elevated in the contralateral spinal dorsal horn (L4 - L6), blocking spinal TNF-α, IL-1β or IL-6 with neutralizing antibodies relieved IL-6-evoked tactile allodynia. Conversely, the levels of anti-inflammatory cytokines TGF-β and IL-10 were reduced in the contralateral spinal dorsal horn (L4 - L6), intrathecal supplement of exogenous TGF-β or IL-10 attenuated IL-6-evoked tactile allodynia. Further studies demonstrated that intrarubral pretreatment with JAK2/STAT3 inhibitor AG490 suppressed the elevations of spinal TNF-α, IL-1β and IL-6 and promoted the expressions of TGF-β and IL-10 in IL-6-evoked tactile allodynia rats. However, intrarubral pretreatment with ERK inhibitor PD98059 only restrained the increase of spinal TNF-α and enhanced the expression of spinal IL-10. These findings imply that rubral IL-6 plays descending facilitation and produces algesic effect through upregulating the expressions of spinal pro-inflammatory cytokines TNF-α, IL-1β, IL-6 and downregulating the expressions of spinal anti-inflammatory cytokines TGF-β and IL-10 by activating JAK2/STAT3 and/or ERK pathways, which provides potential therapy targets for the treatment of pathologic pain.

Details

Title
Red Nucleus Interleukin-6 Evokes Tactile Allodynia in Male Rats Through Modulating Spinal Pro-inflammatory and Anti-inflammatory Cytokines
Author
Yang, Qing-Qing; Li, Hao-Nan; Xia, Yu-Tong; Tian, Xue; Feng, Fan; Yang, Jian; Xu, Ya-Li; Guo, Juan; Li, Xiao-Qi; Wang, Jun-Yang; Zeng, Xiao-Yan
Section
ORIGINAL RESEARCH article
Publication year
2022
Publication date
Apr 8, 2022
Publisher
Frontiers Research Foundation
e-ISSN
1662-5099
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2648319291
Copyright
© 2022. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.