66. Intrathecal administration of microRNA-124 alleviates both neuropathic pain and depression-like behavior in mice

Abstract

MicroRNAs are short non-coding RNAs that regulate gene expression at the transcriptional as well as at the post-transcriptional level. Micro RNA 124 (miR124) is highly expressed in the central nervous system and keeps microglia in a quiescent state. Previously, we have shown that intrathecal administration of miR-124 reduced thermal hyperalgesia in response to peripheral inflammation. Here, we investigated whether miR124 can be used to treat neuropathic pain and comorbid depressive behavior. Intrathecal administration of miR124 starting at day 5 after spared nerve injury (SNI) in mice reversed the existing mechanical hyperalgesia. Depressive-like behavior was measured as increased immobility in a forced swim test. Intrathecal administration of miR124 inhibited this depressive-like behavior. The beneficial effect of miR124 treatment on SNI-induced pain and depressive behavior was associated with a decrease in the expression of the microglial activation marker IBA-1. Moreover, miR124 treatment induced an up regulation of the anti-inflammatory M2 microglial/macrophage marker CD206, while the expression of the pro-inflammatory M1 marker CD16/32 was down regulated in the spinal cord. Our findings indicate that miR124 treats both chronic pain and depressive-like behavior in the SNI model of chronic neuropathic pain by promoting the anti-inflammatory activity of spinal cord microglia/macrophages. Supported by NIH grants NS073939 and NS074999.