Inhibition of miR-665 alleviates neuropathic pain by targeting SOCS1

Mengjia Li,Wenfu Zhang,Yongqiang Lin,Xuyan Chen,Gaofeng Rao

doi:10.4314/tjpr.v19i8.4

Abstract

Purpose: To investigate the effect of miR-665 in neuropathic pain and the possible molecular mechanism involved.Methods: A neuropathic pain model was established using chronic constriction injury (CCI) methods in Sprague Dawley (SD) rats. Mechanical and thermal hyperalgesia were measured using paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), respectively. The inflammation response was determined by assessing the production of inflammation factors. The target relationship of miR-665 and suppressor of cytokine signaling 1 (SOCS1) was verified by luciferase assay.Results: In the CCI rat model, PWT and PWL decreased following treatment with miR-665 (p < 0.01). MiR-665 was elevated in the spinal cord and microglia of CCI rats at different time points (p < 0.01). Down-regulation of miR-665 increased PWT and PWL and inhibited the production of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in CCI rats (p < 0.01). Luciferase assay results indicate that SOCS1 was the target of miR-665 (p < 0.01). SOCS1 decreased in CCI rats (p < 0.01) after treatment with miR-665. MiR-665 negatively regulated the expression of SOCS1 (p < 0.01). Down-regulation of SOCS1 reversed the alleviating effect of decreased miR-665 on pain sensitivity and inflammationresponse (p < 0.01).Conclusion: Down-regulation of miR-665 alleviates neuropathic pain by targeting SOCS1, and hence making miR-665 a promising therapeutic target for neuropathic pain. Keywords: MiR-665, SOCS1, Neuropathic pain, CCI, Spinal cord

Highlights

Chronic neuropathic pain is long-lasting pathological pain triggered by a lesion or disease of the somatosensory system [1]
After the establishment of constriction injury (CCI) rats, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were decreased in the CCI rats compared to the sham rats (p < 0.01, Figure 1 A and B)
The results revealed that CCI rats had increased mechanical and thermal hyperalgesia and that the CCI model was successful

Summary

INTRODUCTION

Chronic neuropathic pain is long-lasting pathological pain triggered by a lesion or disease of the somatosensory system [1]. The down-regulated miR-144 in a neuropathic pain mouse model modulates pain sensitivity and the inflammation response through targeting RAS P21 protein activator 1 (RASA1) [8]. The influences and potential modulation mechanism of miR-665 on hyperalgesia and inflammation response in neuropathic pain induced by CCI were studied. To investigate the effect of mi-665 on pain sensitivity and the production of inflammation factors and to determine the underlying mechanism, the rats in the sham and CCI groups were injected negative control antagomir (NC antagomir), miR-665 antagomir, or shRNA adenovirus plasmid of suppressor of cytokine signaling 1 (SOCS1) (GenePharma, Shanghai, China) in the medullary sheath. Mechanical ectopic pain was assessed by determining the paw withdrawal threshold (PWT) under the von Frey hair test according to methods used in previous studies [6,13].

RESULTS

DISCUSSION

Conflict of interest