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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)-1ß, IL-6, and tumor necrosis factor (TNF)-a 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 inflammation response (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. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of eriodictyol on spinal cord injury (SCI) and its underlying mechanism of action. Methods: Thirty Sprague-Dawley rats were assigned to sham, SCI, and eriodictyol-treated groups (SCI + Eri; 10, 20, and 50 mg/kg). Moderate spinal cord contusion injury was induced to model SCI. Locomotor recovery was assessed based on Basso, Beattie, and Bresnahan (BBB) score. Pain was evaluated by paw withdrawal threshold (PWT) and latency (PWL), and spinal cord water content was measured. Tumor necrosis factor-alpha (TNF-a), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6) expression were determined by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Immunoassay was used to determine malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX) levels while Western blotting was employed to evaluate nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), and phosphorylated NF-κB (p-NF-κB) levels. Results: Eriodictyol elevated BBB score, PWT, and PWL in SCI rats but reduced spinal cord water content (p < 0.05). Eriodictyol treatment down-regulated TNF-a, IL-1ß, IL-6, and MDA, whereas SOD, GSH, and GSH-PX levels were elevated (p < 0.05). Eriodictyol administration increased Nrf2 and HO-1 levels but reduced p-NF-κB/NF-κB. Conclusion: This study provides a potential therapy to promote long-term functional recovery following SCI. [ABSTRACT FROM AUTHOR]