Eukaryotic initiation factor 4 gamma 2 contributes to neuropathic pain through down-regulation of Kv1.2 and the mu opioid receptor in mouse primary sensory neurones. (March 2021)

• Record Type: Journal Article
• Authors: Zhang, Zhen; Zheng, Bixin; Du, Shibin; Han, Guang; Zhao, Hui; Wu, Shaogen; Jia, Shushan; Bachmann, Thomas; Bekker, Alex; Tao, Yuan-Xiang
• Is Part Of: British journal of anaesthesia. Volume 126:Number 3(2021)
• Page Start: 706
• Page End: 719
• Publication Date: 2021-03
• Subjects: dorsal root ganglion -- eIF4G2 -- Kv1.2 -- mu opioid receptor -- neuropathic pain; Anesthesiology -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1016/j.bja.2020.10.032
• Languages: English
• ISSNs: 0007-0912

Abstract

Abstract: Background: Nerve injury-induced changes in gene expression in the dorsal root ganglion (DRG) contribute to neuropathic pain genesis. Eukaryotic initiation factor 4 gamma 2 (eIF4G2) is a general repressor of cap-dependent mRNA translation. Whether DRG eIF4G2 participates in nerve injury-induced alternations in gene expression and nociceptive hypersensitivity is unknown. Methods: The expression and distribution of eIF4G2 mRNA and protein in mouse DRG after spinal nerve ligation (SNL) were assessed. Effects of eIF4G2 siRNA microinjected through a glass micropipette into the injured DRG on the SNL-induced DRG mu opioid receptor (MOR) and Kv1.2 downregulation and nociceptive hypersensitivity were examined. In addition, effects of DRG microinjection of adeno-associated virus 5-expressing eIF4G2 (AAV5- eIF4G2 ) on basal DRG MOR and Kv1.2 expression and nociceptive thresholds were analysed. Results: eIF4G2 protein co-expressed with Kv1.2 and MOR in DRG neurones. Levels of eIF4G2 mRNA (1.7 [0.24] to 2.3 [0.14]-fold of sham, P <0.01) and protein (1.6 [0.14] to 2.5 [0.22]-fold of sham, P <0.01) in injured DRG were time-dependently increased on days 3–14 after SNL. Blocking increased eIF4G2 through microinjection of eIF4G2 siRNA into the injured DRG attenuated SNL-induced downregulation of DRG MOR and Kv1.2 and development and maintenance of nociceptive hypersensitivities. DRG microinjection of AAV5- eIF4G2 reduced DRG MOR and Kv1.2 expression and elicited hypersensitivities to mechanical, heat and cold stimuli in naïve mice. Conclusions: eIF4G2 contributes to neuropathic pain through participation in downregulation of Kv1.2 and MOR in injured DRG and is a potential target for treatment of this disorder.