Abstract
Mlxipl regulates glucose metabolism, lipogenesis and tumorigenesis and has a wide-ranging impact on human health and disease. However, the role of Mlxipl in neuropathic pain remains unknown. In this study, we found that Mlxipl was increased in the ipsilateral L4–L6 spinal dorsal horn after Spared Nerve Injury surgery. Knockdown of Mlxipl in the ipsilateral L4–L6 spinal dorsal horn by intraspinal microinjection aggravated Spared Nerve Injury-induced mechanical allodynia and inflammation in the spinal dorsal horn, on the contrary, overexpression of Mlxipl inhibited mechanical allodynia and inflammation. Subsequently, the rat Mlxipl promoter was analyzed using bioinformatics methods to predict the upstream transcription factor cJun. Luciferase assays and ChIP-qPCR confirmed that cJun bound to the promoter of Mlxipl and enhanced its expression. Finally, we demonstrated that Mlxipl inhibited the inflammatory responses of lipopolysaccharide-induced microglia and that Mlxipl was regulated by the transcription factor cJun. These findings suggested that cJun-induced Mlxipl upregulation in the spinal dorsal horn after peripheral nerve injury provided a protective mechanism for the development and progression of neuropathic pain by inhibiting microglial-derived neuroinflammation. Targeting Mlxipl in the spinal dorsal horn might represent an effective strategy for the treatment of neuropathic pain.
Highlights
Neuropathic pain (NP) is a debilitating clinical condition caused by a lesion or disease of the somatosensory system
Mlxipl was upregulated in ipsilateral spinal dorsal horn (SDH) of SNIinduced mechanical allodynia rats In order to verify that the Spared Nerve Injury (SNI) surgery induced mechanical allodynia, the 50% paw withdraw threshold (50% 50% Paw Withdrawal Threshold (PWT)) of behavior test were examined before and after sham or SNI surgery
The ipsilateral 50% PWT was remarkably elevated after SNI surgery (Figure 1A), while no obvious difference was observed in contralateral side (Figure 1B)
Summary
Neuropathic pain (NP) is a debilitating clinical condition caused by a lesion or disease of the somatosensory system. SDH is a key area that receives, processes and transmits peripheral nociceptive stimulation from dorsal root ganglion afferent. It is widely involved in central sensitization and participates in the development of chronic pain [1]. Recent study demonstrated that Mlxipl protects against atherosclerotic progression in an atherosclerotic model mouse by inhibiting lipopolysaccharide (LPS)-induced proinflammatory cytokines in macrophages [7]. Despite these findings, the role of Mlxipl in neuropathic pain remains poorly understood
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