Abstract

 
 
 
 Purpose: To investigate the effect of miR-339 on neuropathic pain.
 Methods: A rat neuropathic pain model was established through chronic constriction injury (CCI). Expression of miR-339 in spinal cord was determined 14 days later. Microglial inflammatory response was evaluated using immunofluorescence analysis of ionized calcium binding adaptor molecule 1 (Iba1), while IL-6 and TNF-α were assessed by enzyme-linked immunosorbent assay (ELISA). Pain- associated behavioral effects and microglia-related inflammation were investigated after intrathecal administration of miR-339 agomir into rats post-CCI. The target gene of miR-339 involved in neuropathic pain was evaluated by a luciferase reporter assay. Microglia cells were isolated from rats, then treated with lipopolysaccharide (LPS). The LPS-induced inflammatory response in microglia cells was determined using quantitative reverse transcription PCR analysis of IL-6 and TNF-α.
 Results: CCI decreased mechanical allodynia and thermal hyperalgesia thresholds, but increased Iba1, IL-6, and TNF-α in rats. MiR-339 was reduced in rat spinal cord after CCI induction while intrathecal injection of miR-339 agomir alleviated CCI-induced changes in mechanical and thermal hyperalgesia in rats, and reversed expression of Iba1, IL-6, and TNF-α. Furthermore, 6-phosphofructo-2- kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) was identified as a miR-339 target gene, and over- expression of miR-339 decreased the expression of PFKFB3, IL-6, and TNF-α in LPS-induced microglia cells.
 Conclusion: The miR-339/PFKFB3 axis ameliorates CCI-induced neuropathic pain by suppression of microglia inflammatory response, suggesting a novel strategy for neuropathic pain management.
 
 
 
Highlights
Neuropathic pain is a pain syndrome caused by primary lesions or dysfunction of the central or peripheral nervous system [1]
MiR-339 was reduced in dorsal horn of spinal cord in constriction injury (CCI) rats
To establish the neuropathic pain model, rats were subjected to CCI induction
Summary
Neuropathic pain is a pain syndrome caused by primary lesions or dysfunction of the central or peripheral nervous system [1]. Tactile pain is a major feature of neuropathic pain, mainly manifested as harmless tactile stimulation that induces a pain response [1]. Due to the Microglia cells, with the ability to regulate synaptic remodeling and immune surveillance in the central nervous system, underlie neuropathic pain [3]. Drugs targeting microglia might offer potential therapeutic strategies for neuropathic pain [3]. In response to noxious stimuli, microglia cells release inflammatory factors, such as TNF-. Α and IL-1β, and contribute to pain hypersensitivity during neuroimmune activation of neuropathic pain [4]. Administration of microglia inhibitor attenuates pain hypersensitivity in neuropathic pain [4]
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