Dezocine attenuates neuropathic pain by inhibiting ERK1/2 signaling in rats

Abstract

Background Neuropathic pain severely impacts patients’ life quality. Dezocine can be used for the treatment of pain. The present study intended to explore the effects of dezocine in chronic constriction injury (CCI) induced neuropathic pain as well as the possible responsible molecules in rats. Methods There were 3 subgroups, ie, control group, CCI group and dezocine+CCI group. The values of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in rats were determined by a dynamic plantar esthesiometer. The ipsilateral lumbar spinal cords in rats were extracted for the detection of protein levels of phosphorylated-mammalian target of rapamycin (p-mTOR) and p-extracellular signal-regulated kinase 1/2 (p-ERK1/2) by western blot analysis; and the mRNA and protein expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and cyclooxygenase-2 (COX-2) by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results In comparison with control group, there were lower values of PWT and PWL in CCI group, which were partially reversed by dezocine. In addition, compared to control group, the expression levels of p-mTOR, p-ERK1/2, IL-6, TNF-α and COX-2 were upregulated by CCI, which were attenuated by dezocine. Conclusions In conclusion, the analgesic effect of dezocine on CCI induced neuropathic pain might be correlated with inhibiting of the p-mTOR and p-ERK1/2 signaling pathway.

“I’ll Be Back”: The Resurrection of Dezocine

“…A recently posted manuscript awaiting peer review suggests that the antinociceptive effects of dezocine in the CCI model are at least partially mediated through the mTOR/ERK1/2 signaling pathway. 65 The role of dezocine's potent serotonin uptake inhibition in its ability to reduce neuropathic pain is less certain. Serotonin receptors in the dorsal horn of the spinal cord are thought to play a role in pain modulation, especially 5-HT 1A , 5-HT 2A/C , 5-HT 3 , and 5-HT 7 receptors (summarized by Obata 66 ).…”

“…In that study, the antinociceptive effects of dezocine could be partially reversed by intrathecal injection of an α2 adrenergic antagonist (yohimbine) and completely reversed by intrathecal injection of a combination of a mu antagonist (CTAP) and an α2 antagonist (yohimbine) or by depletion of spinal norepinephrine through intrathecal administration of 6-hydroxydopamine. A recently posted manuscript awaiting peer review suggests that the antinociceptive effects of dezocine in the CCI model are at least partially mediated through the mTOR/ERK1/2 signaling pathway …”