Context: Quercetin (que) is one abundant flavonol with a variety of biological activities. Previous studies have shown quercetin can reduce neuropathic pain in rats with chronic constriction injury (CCI). Objective: To evaluate the effects of quercetin on neuropathic pain in CCI model and explore its underlying mechanism in vivo. Materials and Methods: CCI model was established by ligating the sciatic nerve of right leg on the SD rats. They were divided into ten groups: sham group, CCI model, sham+ que, CCI+ que group (30, 60, 120 mg/kg), CCI+ AICAR, CCI+ que+ compound C, CCI+etoricoxib, and the control group. They were administered for 28 days, and were performed the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) during the experiment. At the end of the experiment, sciatic nerves and spinal cord segments of rats were collected, ELISA detected the expression of inflammatory factors, detected the microglia and astrocytes with fluorescence, and Western blot detected AMPK/MAPK pathway. Results: Que could increase the MWT of CCI rats, improve the TWL of plantar, and reduce the inflammatory cells at the ligation site of the sciatic nerve. Also, que could reduce the levels of TNF-α, IL-6, and IL-1β. Western blotting results showed that p-38 MAPK, p-ERK, and p-JNK were activated in the spinal dorsal horn of CCI model group. After treatment with que and AMPK agonists, the phosphorylation levels of related proteins were inhibited. In addition, the analgesic effect of que was abolished when the AMPK inhibitor was added. Discussion and Conclusion: Quercetin alleviated the inflammatory response of sciatic nerve and spinal dorsal horn in rats induced by CCI. Quercetin alleviates neuralgia in CCI rats by activating AMPK pathway and inhibiting MAPK pathway and its downstream targets, p-38, p-ERK, and p-JNK.

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neuropathic pain is rarely diagnosed. oxyntomodulin is peripherally and centrally distributed; however, the potential mechanisms underlying the effects of oxyntomodulin in attenuating nociception remain unclear; thus, we aimed to explore them in the present study. a neuropathic pain model in male c57Bl/6 mice was induced by intrathecal injection of tumor necrosis factor-α (TnF-α), and the duration of nociceptive behavioral responses was measured with a stop-watch timer within 30 min. Western blotting was used to explore the protein levels of ionized calcium binding adaptor molecule-1 (iBa1), nuclear factor-κB (nF-κB) phosphorylated-p65, interleukin (il)-6 and il-1β. We performed reverse transcription-quantitative polymerase chain reaction and eliSa were performed to determine the mrna and protein expression levels of il-6 and il-1β, respectively. an MTT assay was conducted to detect BV2 cell viability. oxyntomodulin was observed to attenuate TnF-α-induced pain hypersensitivity in mice, as well as the expression of iBa1, nF-κB p-p65, il-6 and il-1β in the spinal cord. oxyntomodulin exhibited no cytotoxicity on BV2 cells, and attenuated TnF-α-induced il-6 and il-1β production and release in BV2 cells and culture medium, respectively. collectively, we proposed oxyntomodulin to attenuate TnF-α induced neuropathic pain associated with the release of glial cytokines il-6 and il-1β via inhibiting the activation of the nF-κB pathway.

Context Veratramine may have a potential therapeutic effect for diabetic peripheral neuropathy (DPN). Objective To evaluate whether veratramine ameliorates neuropathic pain in a rat diabetic model. Materials and methods Sprague–Dawley rats were used for a diabetic model induced by a streptozotocin + high-fat diet. Two months after the induction of the diabetic model, the rats with DPN were screened according to the mechanical pain threshold. The rats with DPN were divided into a model group (n = 12) and a treated group (n = 12). Rats with diabetes, but without peripheral neuropathy, were used in the vehicle group (n = 9). The treatment group received 50 μg/kg veratramine via the tail vein once a day for 4 weeks. During modelling and treatment, rats in all three groups were fed a high-fat diet. Results The mechanical withdrawal threshold increased from 7.5 ± 1.9 N to 17.9 ± 2.6 N in DPN rats treated with veratramine. The tolerance time of the treated group to hot and cold ectopic pain increased from 11.8 ± 4.2 s and 3.4 ± 0.8 s to 20.4 ± 4.1 s and 5.9 ± 1.7 s, respectively. Veratramine effectively alleviated L4-L5 spinal cord and sciatic nerve pathological injury. Veratramine inhibited the expression of SIGMAR1 and the phosphorylation of the N-methyl-d-aspartate receptor (NMDAR) Ser896 site in spinal cord tissue, as well as inhibited the formation of SIGMAR1-NMDAR and NMDAR-CaMKII complexes. Discussion and conclusions Veratramine may alleviate the occurrence of pain symptoms in rats with DPN by inhibiting activation of the SIGMAR1-NMDAR pathway.