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J Pain. 2019 Jan 17. pii: S1526-5900(18)30607-2. doi: 10.1016/j.jpain.2019.01.007. [Epub ahead of print]

Bexarotent attenuated CCI-induced spinal neuroinflammation and neuropathic pain by targeting MKP-1.

Author information

1
Department of Anesthesiology, Maternal and Child Hospital of Hunan Province, Changsha, Hunan 410008, China.
2
Department of Endocrinology, Yongzhou-affiliated Hospital of University of South China, Yongzhou 425000, Hunan Province, China.
3
Department of Anesthesiology, Maternal and Child Hospital of Hunan Province, Changsha, Hunan 410008, China. Electronic address: aiyuanli0701@hotmail.com.

Abstract

It is widely accepted that neuroinflammation in the spinal cord contribute to the development of central sensitization in neuropathic pain. MAPKs activation plays an vital role in the development of neuroinflammation in the spinal cord. In this study, we investigated the effect of bexarotene, a RXR agonist, on MAPKs activation in CCI-induced neuropathic pain. The data showed that daily treatment with bexarotene 50mg/kg significantly alleviated CCI-induced nociceptive hypersensitivity in rats. Bexarotene 50mg/kg/day inhibited CCI-induced MAPKs (p38MAPK, ERK1/2, and JNK) activation and upregulation of proinflammatory factors(IL-1β, TNF-α and IL-6). Bexarotene also reversed CCI-induced microglia activation in the ipsilateral spinal cord. Furthermore, bexarotene treatment significantly upregulated MKP-1 in the spinal cord. These effects were completely abrogated by MKP-1 inhibitor BCI. These results indicated that bexarotene relieved CCI-induced neuroinflammation and neuropathic pain by targeting MKP-1. Therefore, bexarotene might be a potential agent for the treatment of neuropathic pain.

KEYWORDS:

Bexarotene; CCI(Chroinc constriction injury); Mitogen-activated protein kinase phosphatase 1(MKP-1); Mitogen-activated protein kinases(MAPKs); Neuropathic pain

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