IRF8 is crucial for the nicotine withdrawal-induced hyperalgesia in mice

Background: Interferon regulatory factor 8 (IRF8) is involved in the pathogenesis of neuropathic pain. However, whether and how IRF8 can regulate the nicotine withdrawal (NTW)-induced hyperalgesia has not been clarified. Methods: C57BL/6 mice were randomized and injected subcutaneously with saline (Control) or nicotine (3 mg/kg) three times per day for 7 consecutive days, followed by injection with mecamylamine to induce NTW. Their paw withdrawal latencies (PWLs) were measured, and the relative levels of IRF8 expression in the spinal cord tissues were determined longitudinally by western blot. The numbers of IRF8+ cells in the spinal cord tissues were examined. In addition, the NTW mice were randomized and infused intrathecally with vehicle saline (NS), control lentivirus or lentivirus for the expression of IRF8-specific shRNA for three days. Their PWLs, microglia activation, IRF8 and P2X4R and BDNF expression in the spinal cord tissues were determined. Results: In comparison with the Control mice, the NTW significantly decreased the PWLs but increased the relative levels of IRF8 expression and the numbers of IRF8+ cells in the spinal cord tissues of mice. IRF8-silencing significantly mitigated the NTW-decreased PWLs and attenuated the NTW-enhanced microglia activation and P2X4R and BDNF expression in the spinal cord tissues of mice. Conclusions: Spinal IRF8 is crucial for the NTW-induced hyperalgesia by enhancing microglia activation and spinal P2X4R and BDNF expression in mice. The IRF8/P2X4R/BDNF axis may be potential therapeutic targets for postoperative pain of smokers.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
IRF8 is crucial for the nicotine withdrawal-induced hyperalgesia in mice ; volume:11 ; number:1 ; year:2020 ; pages:283-293 ; extent:11
Translational Neuroscience ; 11, Heft 1 (2020), 283-293 (gesamt 11)

Creator
Guo, Lina
Zhang, Yang
Wang, Jinping
Qi, Yingying
Zhang, Zongwang

DOI
10.1515/tnsci-2020-0139
URN
urn:nbn:de:101:1-2022111513151325772118
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
15.08.2025, 7:23 AM CEST

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Associated

  • Guo, Lina
  • Zhang, Yang
  • Wang, Jinping
  • Qi, Yingying
  • Zhang, Zongwang

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