Increased miR-195 aggravates neuropathic pain by inhibiting autophagy following peripheral nerve injury

Following peripheral nerve injury (PNI) microglia proliferates and adopts inflammation that contributes to development and maintenance of neuropathic pain. miRNAs and autophagy are two important factors in the regulation of inflammation. However, little is known about whether miRNAs regulate neuroin...

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Bibliographic Details
Published in:Glia 2013-04, Vol.61 (4), p.504-512
Main Authors: Shi, Guodong, Shi, Jiangang, Liu, Kun, Liu, Ning, Wang, Yuan, Fu, Zhiyi, Ding, Jiandong, Jia, Lianshun, Yuan, Wen
Format: Article
Language:English
Subjects:
Animals
Autophagy
Autophagy - genetics
Cells, Cultured
Down-Regulation - genetics
Inflammation - genetics
Inflammation - metabolism
Inflammation - pathology
Male
Medical research
Microglia - metabolism
Microglia - pathology
MicroRNAs - antagonists & inhibitors
MicroRNAs - biosynthesis
MicroRNAs - physiology
miR-195
Neuralgia - genetics
Neuralgia - metabolism
Neuralgia - pathology
neuroinflammation
neuropathic pain
Pain management
Peripheral Nerve Injuries - genetics
Peripheral Nerve Injuries - metabolism
Peripheral Nerve Injuries - pathology
peripheral nerve injury
Rats
Rats, Wistar
Up-Regulation - genetics
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Summary:Following peripheral nerve injury (PNI) microglia proliferates and adopts inflammation that contributes to development and maintenance of neuropathic pain. miRNAs and autophagy are two important factors in the regulation of inflammation. However, little is known about whether miRNAs regulate neuroinflammation and neuropathic pain by controlling autophagy. In the study, we demonstrated that miR‐195 levels were markedly increased in rats subjected to L5 spinal nerve ligation (SNL). Upregulated miR‐195 was also found in spinal microglia of rats with SNL. The overexpression of miR‐195 contributed to lipopolysaccharide‐induced expression of proinflammatory cytokines IL‐1β, TNF‐α, and iNOS in cultured microglia. Upregulated miR‐195 also resulted in increased mechanical and cold hypersensitivity after PNI, whereas miR‐195 inhibition reduced mechanical and cold sensitivity. We further demonstrated that PNI significantly inhibited microglial autophagy activation, whereas miR‐195 inhibitor treatment increased autophagy activation and suppressed neuroinflammation in vivo and in vitro. More important, autophagy inhibition impaired miR‐195 inhibitor‐induced downregulation of neuroinflammation and neuropathic pain. Additionally, ATG14 was identified as the functional target of miR‐195. Conclusions: These data demonstrated that miR‐195/autophagy signaling represents a novel pathway regulating neuroinflammation and neuropathic pain, thus offering a new target for therapy of neuropathic pain.
ISSN:0894-1491
1098-1136
DOI:10.1002/glia.22451