Previous studies suggest that dexmedetomidine has a protective effect against local anaesthetic-induced nerve injury in regional nerve blocks. Whether this potentially protective effect exists in the context of diabetes mellitus is unknown. A diabetic state was established in adult male Sprague-Dawley rats with intraperitoneal injection of streptozotocin. Injections of ropivacaine 0.5%, dexmedetomidine 20 μg kg-1 (alone and in combination), or normal saline (all in 0.2 ml) were made around the sciatic nerve in control and diabetic rats (n=8 per group). The duration of sensory and motor nerve block and the motor nerve conduction velocity (MNCV) were determined. Sciatic nerves were harvested at post-injection day 7 and assessed with light and electron microscopy or used for pro-inflammatory cytokine measurements. Ropivacaine and dexmedetomidine alone or in combination did not produce nerve fibre damage in control non-diabetic rats. In diabetic rats, ropivacaine induced significant nerve fibre damage, which was enhanced by dexmedetomidine. This manifested with slowed MNCV, decreased axon density, and decreased ratio of inner to outer diameter of the myelin sheath (G ratio). Demyelination, axon disappearance, and empty vacuoles were also found using electron microscopy. An associated increase in nerve interleukin-1β and tumour necrosis factor-α was also seen. Ropivacaine 0.5% causes significant sciatic nerve injury in diabetic rats that is greatly potentiated by high-dose dexmedetomidine. Although the dose of dexmedetomidine used in this study is considerably higher than that used in clinical practice, our data suggest that further studies to assess ropivacaine (alone and in combination with dexmedetomidine) use for peripheral nerve blockade in diabetic patients are warranted.

Introduction: Painful diabetic neuropathy (PDN) is a common complication of diabetes. Previous studies have implicated that mitochondrial dysfunction plays a role in the development of PDN, but its pathogenesis and mechanism have not been fully investigated.Methods: In this study, we used high‐fat diet/low‐dose streptozotocin‐induced rats as a model of type 2 diabetes mellitus. Behavioral testing, whole‐cell patch‐clamp recordings of dorsal root ganglion (DRG) neurons, and complex sensory nerve conduction velocity studies were used to assess peripheral neuropathy. Mitochondrial membrane potential (MMP), ATP, tissue reactive oxygen species, and transmission electron microscopy were used to evaluate the function and morphology of mitochondria in DRG. Real‐time PCR, western blot, and immunofluorescence were performed to investigate the mechanism.Results: We found that damaged mitochondria were accumulated and mitophagy was inhibited in PDN rats. The expression of sirtuin 3 (SIRT3), which is an NAD⁺‐dependent deacetylase in mitochondria, was inhibited. Overexpression of SIRT3 in DRG neurons by intrathecally administered LV‐SIRT3 lentivirus ameliorated neurological and mitochondrial dysfunctions. This was evidenced by the reversal of allodynia and nociceptor hyperexcitability, as well as the restoration of MMP and ATP levels. Overexpression of SIRT3 restored the inhibited mitophagy by activating the FoxO3a‐PINK1‐Parkin signaling pathway. The effects of SIRT3 overexpression, including the reversal of allodynia and nociceptor hyperexcitability, the improvement of impaired mitochondria and mitophagy, and the restoration of PINK1 and Parkin expression, were counteracted when FoxO3a siRNA was intrathecally injected.Conclusion: These results showed that SIRT3 overexpression ameliorates PDN via activation of FoxO3a‐PINK1‐Parkin‐mediated mitophagy, suggesting that SIRT3 may become an encouraging therapeutic strategy for PDN.

Ultrasound guidance has reduced the amount of local anesthetics to achieve a successful block. Previous studies of the relationship between the volume or concentration of local anesthetics and the effects of the block were based on relatively high doses of local anesthetics. We tested the hypothesis that providing low dose of ropivacaine at three combinations of volumes and concentrations for ultrasound-guided interscalene brachial plexus block would produce different effects in the aspect of onset time, pain control and the incidence of side effects. Ninety-nine patients undergoing elective arthroscopic shoulder surgery were randomized to receive an ultrasound guided combined with nerve stimulator mediated interscalene block with ropivacaine 0.75 % (6.7 ml, Group 0.75), 0.5 % (10 ml, Group 0.5) or 0.25 % (20 ml, Group 0.25). The primary end point was the onset time of the sensory blockade, assessed by using a pinprick in the C5-6 dermatome. The secondary end points included the onset time of the motor blockade, block success rate, postoperative pain rating score, rescue analgesics requirement, sleep quality, strength of the hand on the block side,and the incidence of hemi-diaphragmatic paresis which was evaluated by ultrasonography. There was a statistically significant difference of the sensory block median onset times among Group 0.75 (5 min), Group 0.5 (10 min) and Group 0.25 (20 min). One patient in Group 0.5 and 20 patients in Group 0.25 did not achieve a complete motor block within 30 min, which were also significantly different. No significant difference was observed in postoperative analgesia, decrease of handgrip strength and the incidence of hemi-diaphragmatic paresis among the 3 groups. This study demonstrates that ropivacaine 50 mg as 0.25, 0.5 or 0.75 % solution for interscalene brachial plexus block before arthroscopic shoulder surgery produces comparable blockade with few side effects, while 0.75 % seems to be more preferable as it is associated with faster onset time. ChiCTR-TRC-13004058 . Registered 4 December 2013.

Background: More than half of cancer patients develop severe chemotherapy-induced peripheral neuropathy (CIPN), resulting in low quality of life, negative effects on function, and challenges in treatment compliance. Most recent studies have shown that exercise therapy has a positive impact on reducing CIPN symptoms and can also improve quality of life, balance, and activity levels. The aim of this meta-analysis was to evaluate the effect of exercise therapy on the efficacy of CIPN.Methods: Computerized search of Embase, Web of Science, CNKI, Wan Fang Data, VIP, CBM for RCTs on exercise therapy for CIPN from database creation to November 2022, without language restriction. The Cochrane Handbook 5.3 risk of bias assessment tool was used to evaluate the quality of the included studies. Then Revman 5.3 software was used to evaluate the quality of the included studies. The heterogeneity of the research results is tested by I², continuous variables were presented as weighted mean difference or standard mean difference, and confidence intervals were set at 95%. Stata15.0 was utilized to conduct a meta-analysis.Results: A total of 15 RCTs with 1,124 patients were included. Meta-analysis showed that the test group was superior to the control group in terms of total symptom score (SMD: −0.62; 95% Cl: −0.99, −0.24), numbness, tingling, quality of life score (total score, physical, function), pain, balance, and neurotoxicity function assessment (FACT/GOG-NTX) questionnaire (p < 0.05).Limitations: The duration and frequency of treatment are different every week, which may have some impact on the results.Conclusion: Exercise therapy can be effective in treating CIPN by improving symptom score (total symptom score, numbness, tingling), quality of life score (total score, physical function), pain, balance, and FACT/GOG-NTX questionnaires. It still needs to be refined and validated by more high-quality, multicenter, large-sample RCTs in the future.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373131, identifier: CRD42022373131.

Background and purpose: Acupuncture is widely used in clinical practice for the treatment of vascular diseases. However, the protocol, efficacy, and mechanism of acupuncture in animal models of vascular dementia are still controversial. Based on the above problems, we initiated this comprehensive study.Methods: To analyze the literatures included in this study, 4 databases were searched and the SYRCLE's Risk of bias tool was employed. To perform the subgroup analysis of different acupuncture methods and the Review Manager 5.3 was applied. Meanwhile, the pairwise and network meta-analysis were conducted using Addis 1.16.8. The outcomes included escape latency, number of crossings, time spent in the target quadrant, and swimming speed.Results: Forty-two studies with a total of 1,486 animals were included in this meta-analysis. According to the results from subgroup analysis, GV20 + ST36 (Baihui + bilateral Zusanli) combined with 14-day manual acupuncture can obtain best improvement of the rats cognitive function among all acupuncture regimens (MD: −23.41; 95%CI: −26.66, −20.15; I² = 0%; P < 0.001). The heterogeneity of other acupuncture treatments was significantly higher than that of GV20 + ST36, because the treatment courses were not uniform. Pair-wise and network comparisons are highly consistent. The major results of the network meta-analysis were as follows, In comparison to the impaired group, the acupuncture group showed significantly reduced escape latency (MD: −25.87; 95%CI: −30.75, −21.12), increased number of original platform crossings (MD: 2.63; 95%CI: 1.94, 3.34) and time spent in the target quadrant (MD: 7.88; 95%CI: 4.25, 11.44). The overall results of the network meta-analysis are as follows: the normal and sham-operated groups performed the best, followed by medicine and acupuncture, while no effect was found in the impaired group treated with non-acupoint and palliative.Conclusions: Acupuncture significantly improves cognitive function in rats with vascular dementia. Compared to other acupuncture plans, (GV20 + ST36, MA) and 14 -day manual acupuncture can be used to obtain better results. The main mechanism of acupuncture in the treatment of vascular dementia is reduced oxidative stress, neuronal inflammation, and apoptosis, as well as the increased synaptic plasticity and neurotransmitters.Systematic review registration: https://inplasy.com/inplasy-2021-11-0036/, identifier: INPLASY2021110036.

Painful diabetic neuropathy (PDN) is one of the most common complications of diabetes. Recent studies suggested that gut microbiota dysbiosis contributes to the development of PDN, but underlying mechanisms remain elusive. In this study, we found decreased probiotics generating bacteria such as Lactobacillus and Bifidobacterium strains in the PDN rats. Supplementation with multiple probiotics for 12 weeks alleviated pain, reversed nerve fiber lesions, and restored neuronal hyperexcitability. Probiotics administration effectively attenuated intestinal barrier impairment, reduced serum lipopolysaccharide and proinflammatory cytokines, and mitigated disruptions in the blood-nerve barrier. Furthermore, probiotics treatment inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway and reduced proinflammatory cytokines in the sciatic nerve of the PDN rats. Together, our findings suggest that gut microbiota dysbiosis participates in PDN pathogenesis, and probiotics offer therapeutic potential via modulating the microbiota-gut-nerve axis.