Dexmedetomidine Relieves Neuropathic Pain in Rats With Chronic Constriction Injury via the Keap1-Nrf2 Pathway.

This study aimed to determine the role of dexmedetomidine (Dex) in neuropathic pain (NP) after chronic constriction injury (CCI) in a rat model as well as its underlying mechanism. First, a CCI rat model was established. After treatment with Dex, the severity of NP was ascertained by monitoring paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) at different time points. Immunohistochemical analysis was performed to determine the levels of Keap1 and Nrf2 in the spinal cord. Furthermore, the levels of Keap1-Nrf2-HO-1 pathway molecules, apoptotic proteins, and antioxidant genes in the spinal cord or isolated primary microglia were determined using quantitative polymerase chain reaction and western blotting. The release of proinflammatory cytokines was detected via enzyme-linked immunosorbent assay. To evaluate Dex-treated CCI-induced NP via the Keap1-Nrf2-HO-1 pathway, the rats were intrathecally injected with lentivirus to upregulate or downregulate the expression of Keap1. We found that Dex inhibited pathological changes and alleviated sciatic nerve pain as well as repressed inflammation, apoptosis, and redox disorders of the spinal cord in CCI rats. Keap1 protein expression was substantially downregulated, whereas Nrf2 and HO-1 expressions were significantly upregulated in the spinal cord after Dex administration. Additionally, Keap1 overexpression counteracted Dex-mediated inhibition of NP. Keap1 overexpression led to a decrease in Nrf2 and HO-1 levels as well as PWT and PWL but led to an aggravation of inflammation and antioxidant disorders and increased apoptosis. Keap1 silencing alleviated NP in rats with CCI, as evidenced by an increase in PWT and PWL. Keap1 depletion resulted in the alleviation of inflammation and spinal cord tissue injury in CCI rats. Collectively, these findings suggest that Dex inhibits the Keap1-Nrf2-HO-1-related antioxidant response, inflammation, and apoptosis, thereby alleviating NP in CCI rats.

Dexmedetomidine relieves formaldehyde-induced pain in rats through both α2 adrenoceptor and imidazoline receptor.

Dexmedetomidine (DEX) is a highly selective α2 adrenergic receptor agonist. In this study, we investigated the analgesic effect and the underlying mechanisms of DEX on inflammatory visceral pain in rats. Twenty-five male Sprague Dawley (SD) rats were randomly divided into 5 groups, including control, sham, low dose DEX, medium dose DEX and high dose DEX group. Pain was induced with 10% formalin and scored every 15min till 2 h-post the induction. Hematoxylin-eosin (HE) staining was used to evaluate the toxicity of DEX on spinal cord neurons. Acetycholine (Ach) and noradrenaline (NA) levels were determined by using ELISA method. The expressions of natural nitric oxide synthase (nNOS), protein kinase γ (PKCγ) and protease-activated receptor 2 (PAR2) were determined by using western blot. DEX treatment relieved formaldehyde-induced pain in rats in a dose-dependent manner. Furthermore, DEX showed little neuro-toxicity on the spinal cord neurons, even at the highest dosage used in our study. Ach level was significantly increased in Sham group compared with control group. DEX treatment decreased NA levels and increased Ach levels in the incubation medium of spinal cord sections. Western blot analysis showed that the expression of nNOS, PKCγ and PAR2 was significantly decreased in DEX group compared with Sham group, whereas these effects of DEX on nNOS, PKCγ and PAR2 were blocked by both yohimbine and idazoxan, indicating that the analgesic effect of DEX is mediated by both α2 adrenergic receptor and imidazoline receptor. Yohimbine and idazoxan treatment significantly enhanced pain scores compared to DEX group, and which antagonizes the effects DEX. In conclusion, our study demonstrated that DEX could inhibit formaldehyde-induced pain by inhibiting nNOS, PKCγ and PAR2 expression through α2 adrenergic receptor and imidazoline receptor.

The effects of neuromuscular blockade on operating conditions during general anesthesia for spinal surgery.

BACKGROUND: Muscle relaxants are prescribed routinely for patients undergoing general anesthesia, but the requirement for paralysis in spinal surgery is unclear. This study compared the operating conditions of general anesthesia with and without a muscle relaxant on spinal surgery patients. METHODS: Eighty-six adults who underwent elective spinal surgery were randomly assigned to a relaxant group (group R) or a no-relaxant group (group NR). All patients were induced with intravenous midazolam (0.05 mg/kg), fentanyl (4 µg/kg), propofol (1.0 mg/kg), and succinylcholine (2 mg/kg) and then atracurium was used in group R but not in group NR. The operating conditions, including muscle tone, body movements, airway pressure, anesthetics consumption, eye-opening time, extubation time, and the Observer's Assessment of the Alertness/Sedation (OAA/S) score 20 minutes after the extubation were compared between the 2 groups. RESULTS: The operating conditions including muscle tone scales, body movements, and airway pressure did not differ between the 2 groups. Eye-opening time (9.35±2.34 vs. 11.02±2.50 min; P=0.002) and extubation time (13.95±3.41 vs. 16.72±3.67 min; P=0.001) were shorter in group NR than in group R. The BIS score at extubation (87.2±5.0 vs. 83.3±5.7; P=0.001) and the OAA/S score 20 minutes after extubation (5 [3 to 5] vs. 4 [3 to 5]; P=0.005) were significantly higher in group NR than in group R. Propofol consumption was higher in group NR than in group R (4206.10±415.80 vs. 3900.60±365.40 µg/kg, respectively; P=0.001). CONCLUSIONS: General anesthesia without muscle relaxant provides similar working conditions to those observed with muscle relaxant, and it is associated with earlier eye opening and extubation and higher level of consciousness on emergence from spinal surgery.