Bexarotent Attenuated Chronic Constriction Injury-Induced Spinal Neuroinflammation and Neuropathic Pain by Targeting Mitogen-Activated Protein Kinase Phosphatase-1

• Published in: The journal of pain Vol. 21; no. 11-12; pp. 1149 - 1159
• Main Authors: Gui, Yulong, Duan, Shunyuan, Xiao, Lihong, Tang, Jing, Li, Aiyuan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2020
• Subjects: Bexarotene; CCI (chronic constriction injury); mitogen-activated protein kinase phosphatase 1 (MKP-1); mitogen-activated protein kinases (MAPKs); neuropathic pain; Bexarotene; neuropathic pain; mitogen-activated protein kinases (MAPKs); CCI (chronic constriction injury); mitogen-activated protein kinase phosphatase 1 (MKP-1)
• ISSN: 1526-5900; 1528-8447
• DOI: 10.1016/j.jpain.2019.01.007

•Bexarotene (bex) decreased chronic constriction injury-induced neuropathic pain in rats.•Bex inhibited chronic constriction injury-induced neuroinflammation and activation of mitogen-activated protein kinases in the spinal cord.•Bex induced mitogen-activated protein kinase phosphatase 1 in the spinal cord.•BCI, a mitogen-activated protein kinase phosphatase 1 inhibitor completely abrogated bex-induced effects in rates with chronic constriction injury.•Bex could be a potential therapeutic agent for neuropathic pain. It is widely accepted that neuroinflammation in the spinal cord contributes to the development of central sensitization in neuropathic pain. Mitogen-activated protein kinase (MAPK) activation plays a vital role in the development of neuroinflammation in the spinal cord. In this study, we investigated the effect of bexarotene (bex), a retinoid X receptor agonist, on MAPKs activation in chronic constriction injury (CCI)-induced neuropathic pain. The data showed that daily treatment with bex 50 mg/kg significantly alleviated CCI-induced nociceptive hypersensitivity in rats. Bex 50 mg/kg/day inhibited CCI-induced MAPKs (p38MAPK, ERK1/2, and JNK) activation and upregulation of proinflammatory factors (IL-1β, tumor necrosis factor-α and IL-6). Bex also reversed CCI-induced microglia activation in the ipsilateral spinal cord. Furthermore, bex treatment significantly upregulated MKP-1 in the spinal cord. These effects were completely abrogated by MKP-1 inhibitor BCI. These results indicated that bex relieved CCI-induced neuroinflammation and neuropathic pain by targeting MKP-1. Therefore, bex might be a potential agent for the treatment of neuropathic pain. Bex could relieve neuropathic pain behaviors in animals by reversing MKP-1 downregulation and MAPKs activation in the spinal cord. Therapeutic applications of bex may be extended beyond cutaneous T-cell lymphoma.