Propofol alleviates neuropathic pain in chronic constriction injury rat models via the microRNA-140-3p/Jagged-1 peptide/Notch signaling pathway.

Chronic constriction injury (CCI) of the sciatic nerve was used to establish neuropathic pain (NP) models in rats. CCI rats were then treated with propofol (Pro) and their paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured. In addition, the expression patterns of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-10 were detected. CCI rats treated with propofol were further injected with antagomiR-140-3p to verify the role of miR-140-3p in propofol's analgesic actions. In addition to confirming the relationship between miR-140-3p and JAG1, the expression patterns of JAG1 itself were detected. Propofol-treated CCI rats were also injected with Ad-JAG1 (adenovirus-packaged JAG1 overexpression vector and Ad-NC) to test the role of JAG1 in propofol's analgesic mechanism of action. Finally, the levels of JAG1 and Notch pathway-related proteins were detected RESULTS: Propofol was found to alleviate NP, including thermal hyperalgesia and mechanical pain threshold. Propofol could also ameliorate neuroinflammation by up-regulating the expression of IL-10 and inhibiting the release of TNF-α and IL-1ß. Mechanically, propofol enhanced the amount of miR-140-3p in CCI rats via the regulation of JAG1. Down-regulation of miR-140-3p, or up-regulation of JAG1, could reduce the protective effect of propofol against NP. Propofol inhibited the activation of Notch signaling via miR-140-3p/JAG1 to realize its analgesic effect CONCLUSION: Our findings indicated that propofol inhibits inflammatory responses and the Notch signaling pathway via miR-140-3p/JAG1 to alleviate NP. These data provide evidence to support a potential clinical therapy for NP.

Dexmedetomidine inhibits the NF-κB pathway and NLRP3 inflammasome to attenuate papain-induced osteoarthritis in rats.

Context: Dexmedetomidine (Dex) has been reported to have an anti-inflammatory effect. However, its role on osteoarthritis (OA) has not been explored. Objective: This study investigates the effect of Dex on OA rat model induced by papain. Materials and methods: The OA Wistar rat model was induced by intraluminal injection of 20 mL of papain mixed solution (4% papain 0.2 mL mixed with 0.03 mol L-1 l-cysteine 0.1 mL) into the right knee joint. Two weeks after papain injection, OA rats were treated by intra-articular injection of Dex (5, 10, or 20 µg kg-1) into the right knee (once a day, continuously for 4 weeks). Articular cartilage tissue was obtained after Dex treatment was completed. Results: The gait behavior scores (2.83 ± 0.49), PWMT (15.2 ± 1.78) and PTWL (14.81 ± 0.92) in H-DEX group were higher than that of OA group, while Mankin score (5.5 ± 0.81) was decreased (p < 0.05). Compared with the OA group, the IL-1ß (153.11 ± 16.05 pg mg-1), IL-18 (3.71 ± 0.7 pg mg-1), IL-6 (14.15 ± 1.94 pg/mg) and TNF-α (40.45 ± 10.28 pg mg-1) levels in H-DEX group were decreased (p < 0.05). MMP-13, NLRP3, and caspase-1 p10 expression in Dex groups were significantly lower than that of OA group (p < 0.05), while collagen II was increased (p < 0.05). p65 in the nucleus of Dex groups was significantly down-regulated than that of OA group (p < 0.05). Discussion and Conclusions: Dex can improve pain symptoms and cartilage tissue damage of OA rats, which may be related to its inhibition of the activation of NF-κB and NLRP3 inflammasome.

Lutein protects against ischemia/reperfusion injury in rat skeletal muscle by modulating oxidative stress and inflammation.

BACKGROUND: Lutein is an antioxidant compound with potential biological effects. The present study investigated the protective role of Lutein against I/R injury in skeletal muscle. METHODS: Animals were divided into three groups. Group I - sham operated; Group II- IR injury- Hind limb ischemia was induced by clamping the common femoral artery and vein. After 4 h of ischemia, the clamp was removed and the animals underwent 2 h of reperfusion. Group III-Lutein + IR injury- Rats with Lutein treatment received intraperitoneal injection 1 h before reperfusion. The skeletal tissues were analyzed for oxidative stress parameters (reactive oxygen species, protein carbonylation and sulfhydryls, lipid peroxidation). Antioxidant status was determined by evaluating Nrf-2 levels and antioxidant enzyme activities. The inflammatory mechanism was determined through NF-κB and COX-2 expressions. Pro-inflammatory cytokines were determined by ELISA. RESULTS: The results showed that Lutein treatment significantly decreased the oxidative stress by reducing reactive oxygen species, protein carbonylation and sulphydryls, lipid peroxidation. Further, the levels of Nrf-2 and antioxidant status was significantly declined during IR injury compared to sham operated rats. Lutein treatment reduced the oxidative stress by enhancing Nrf-2 levels and antioxidant status. Skeletal IR injury enhanced the inflammatory signaling by up regulating NF-κB, COX-2 and various pro-inflammatory cytokines. NF-κB, COX-2 expressions were down regulated by Lutein treatment. CONCLUSION: The study shows that Lutein protects against skeletal IR injury by down regulating oxidative stress and inflammatory mechanisms.

The Role of NF mRNA and Calpain in NF Reduction of Acrylamide Neuropathy.

The purpose of this study was to study the role of neurofilament (NF) mRNA and calpain in NF reduction of acrylamide (ACR) neuropathy. Male Wistar adult rats were injected i.p. every other day with ACR (20 mg/kg·bW or 40 mg/kg·bW) for 8 weeks. NF mRNA expression was detected using RT-PCR and the calpain concentration was determined using western blot analysis. The NF mRNA expression significantly decreased while the level of m-calpain and µ-calpain significantly increased in two ACR-treated rats groups regardless of the ACR dose. The light NF (NF-L) protein expression was significantly correlated with NF-L mRNA expression. Combined with previous data, the concentrations of three NF subunits were negatively correlated with the calpain levels. These findings suggest that NF-L mRNA and calpain mediated the reduction in NF of ACR neuropathy.