Analgesic Effect of Exercise on Neuropathic Pain via Regulating the Complement Component 3 of Reactive Astrocytes.

BACKGROUND: Exercise has been proven to be an efficient intervention in attenuating neuropathic pain. However, the underlying mechanisms that drive exercise analgesia remain unknown. In this study, we aimed to examine the role of complement component 3 (C3) in neuropathic pain and whether antinociceptive effects are produced by exercise via regulating C3 in mice. METHODS: In this study, using a spared nerve injury (SNI)-induced neuropathic pain mice model, C57BL/6J mice were divided into 3 groups: Sham mice, SNI mice, and SNI + Exercise (Ex) mice with 30-minute low-intensity aerobic treadmill running (10 m/min, no inclination). Paw withdrawal threshold; thermal withdrawal latency; and glial fibrillary acidic protein, C3, tumor necrosis factor-α, and interlukin-1ß expression in the spinal cord were monitored. C3 knockout (KO) mice were further used to verify the role of C3 in neuropathic pain. RESULTS: von Frey test, acetone test, and CatWalk gait analysis revealed that treadmill exercise for 4 weeks reversed pain behaviors. In addition, exercise reduced astrocyte reactivity (SNI mean = 14.5, 95% confidence interval [CI], 12.7-16.3; SNI + Ex mean = 10.3, 95% CI, 8.77-11.9, P = .0003 SNI + Ex versus SNI) and inflammatory responses in the spinal cord after SNI. Moreover, it suppressed the SNI-induced upregulation of C3 expression in the spinal cord (SNI mean = 5.46, 95% CI, 3.39-7.53; SNI + Ex mean = 2.41, 95% CI, 1.42-3.41, P = .0054 SNI + Ex versus SNI in Western blot). C3 deficiency reduced SNI-induced pain and spinal astrocyte reactivity (wild type mean = 7.96, 95% CI, 6.80-9.13; C3 KO mean = 5.98, 95% CI, 5.14-6.82, P = .0052 C3 KO versus wild type). Intrathecal injection of recombinant C3 (rC3) was sufficient to produce mechanical (rC3-Ex mean = 0.77, 95% CI, 0.15-1.39; rC3 mean = 0.18, 95% CI, -0.04 to 0.41, P = .0168 rC3-Ex versus rC3) and cold (rC3-Ex mean = 1.08, 95% CI, 0.40-1.77; rC3 mean = 3.46, 95% CI, 1.45-5.47, P = .0025 rC3-Ex versus rC3) allodynia in mice. Importantly, exercise training relieved C3-induced mechanical and cold allodynia, and the analgesic effect of exercise was attenuated by a subeffective dose of intrathecal injection of C3. CONCLUSIONS: Overall, these results suggest that exercise suppresses neuropathic pain by regulating astroglial C3 expression and function, thereby providing a rationale for the analgesic effect of exercise as an acceptable alternative approach for treating neuropathic pain.

Effect of TGF-ß1-Mediated Exercise Analgesia in Spared Nerve Injury Mice.

Peripheral nerve injury leads to severe neuropathic pain. Previous studies have highlighted the beneficial effects of physical exercise on alleviating neuropathic pain. Exercise regulating transforming growth factor-ß1 (TGF-ß1) can improve several diseases and relieve neuropathic pain induced by peripheral nerve injury. Here, we investigated whether exercise could alleviate neuropathic pain by modulating TGF-ß1 expression. We assessed mechanical and cold pain behavior and conducted molecular evaluation of the spinal cord. We found that spared nerve injury (SNI) led to mechanical and cold allodynia in the hind paw, elevated the expression of latency-associated peptide- (LAP-) TGF-ß1, and activated astroglial in the spinal cord. Exercise decreases allodynia, astroglial activation, and LAP-TGF-ß1 in SNI mice. Intrathecal injection of a TGF-type I receptor inhibitor attenuated exercise analgesia and enhanced astroglial activation. These findings demonstrate that exercise induces analgesia by promoting TGF-ß1 activation and inhibiting astrogliosis. Our study reveals a new underlying mechanism for exercise-attenuated neuropathic pain in the maintenance stage of neuropathic pain after nerve injury.

A Meta-Analysis of the Effects of Aerobic Exercise on the Basal Level of Endothelial Progenitor Cells in Middle-Aged and Older Adults.

Circulatory endothelial progenitor cells (EPCs) play an important role in repairing damaged vascular endothelium and preventing cardiovascular diseases. The decrease in level of circulating EPCs in middle-aged and older adults can lead to an increase in cardiovascular events. Researchers have carried out several studies on the effects of aerobic exercise on circulating EPCs in middle-aged and older adults, but the results vary from one study to another. The aim of this study therefore is to systematically evaluate the effect of aerobic exercise on the basal level of circulating EPCs in middle-aged and older adults by meta-analysis. Randomized controlled trial studies on the effects of aerobic exercise on EPCs were searched for from CNKI, PubMed, EBSCO, Cochrane Library, Web of Science, and Embase databases. The literature was screened according to inclusion and exclusion criteria, research data were extracted, and the literature quality was evaluated by Cochrane scale. Software Review Manager (version 5.3) and Stata (version 15.0) were used for data analysis. A total of nine articles were included in this analysis, including 165 participants (40 healthy adults and 125 patients) who received exercise interventions and 162 participants (40 healthy adults and 122 patients) who served as the control, with an age range from 58 to 70 years. The meta-analysis found that long-term (≥12 weeks) aerobic exercise could improve the level of EPCs in the peripheral circulation (standardized mean differences [SMD] = 0.53, 95% confidence interval [0.30, 0.76], p < .01). The subgroup analysis found that aerobic exercise improved EPCs in healthy people better than in people with cardiovascular disease and that the intervention time needs to be over 12 weeks to have a significant impact. In conclusion, the authors suggest that middle-aged and older adults can improve their EPCs quantity by engaging in moderate-intensity aerobic exercise four to five times per week for no less than 12 weeks to reduce the risk of cardiovascular disease.

Validity of Apple Watch 6 and Polar A370 for monitoring energy expenditure while resting or performing light to vigorous physical activity.

OBJECTIVES: The purpose of this study was to assess the validity of energy expenditure measurements taken by the Apple Watch 6 and Polar A370 during resting, light- to vigorous-intensity running on the treadmill and ground, and post-exercise of each speed. DESIGN: Randomized cross-over trial. METHODS: This study included 11 male adults (22.5 ±â€¯1.8 years old). Participants were asked to wear the Apple Watch 6 and the Polar A370 simultaneously to measure energy expenditure under various intensities of physical activities on the treadmill and ground, which were then compared with results from a gas metabolism analysis system. RESULTS: Monitoring energy expenditure for both treadmill and ground, the Apple Watch 6 (range: 13.40-50.34 %) had a higher mean absolute percent error than the Polar A370 (range: 12.74-27.70 %) in resting and running state, while the mean absolute percent error of the Apple Watch 6 (range: 9.71-32.81 %) is smaller than that of the Polar A370 (15.79-43.51 %) in post-exercise. The Apple Watch 6 tends to overestimate energy expenditure, with a mean percent error ranging from -6.61 % to 53.24 %, while the Polar A370 tends to underestimate energy expenditure, with a mean percent error ranging from -3.51 % to 11.33 %. No estimated energy expenditure of both devices fell in the equivalence testing zone. CONCLUSIONS: For young adult males, the Apple Watch 6 and Polar A370 provide similar levels of accuracy in monitoring energy expenditure during treadmill and ground running exercise. However, both devices are still inadequate in this regard.

The Mechanism of miR-21-5p/TSP-1-Mediating Exercise on the Function of Endothelial Progenitor Cells in Aged Rats.

(1) Background: The declined function of peripheral circulating endothelial progenitor cells (EPCs) in aging individuals resulted in decreased endothelial cell regeneration and vascular endothelial function. Improving EPCs function in aging individuals plays an important role in preventing cardiovascular diseases. (2) Methods: Thirty aged (18-month-old) male Sprague-Dawley rats were randomly divided into control and exercise groups. An aerobic exercise intervention was performed 5 days/week for 8 weeks. EPCs functions, miR-21-5p, and TSP-1 expressions were detected after the intervention. The senescence rate, proliferation, and migration of EPCs were examined after overexpression of miR-21-5p and inhibition of TSP-1 expression. (3) Results: The senescence rate, proliferation, and migration of EPCs in exercise groups were significantly improved after exercise intervention. The miR-21-5p expression was increased and the TSP-1 mRNA expression was decreased in the EPCs after the intervention. miR-21-5p overexpression can improve EPCs function and inhibit TSP-1 expression but has no effect on senescence rate. Inhibition of TSP-1 expression could improve the function and reduce the senescence rate. (4) Conclusions: Our results indicate that long-term aerobic exercise can improve the functions of EPCs in aging individuals by downregulating TSP-1 expression via miR-21-5p, which reveals the mechanism of exercise in improving cardiovascular function.

The effects of HIIT compared to MICT on endothelial function and hemodynamics in postmenopausal females.

OBJECTIVE: The study was designed to investigate the role of exercise in ameliorating endothelial function and hemodynamics in postmenopausal females, and compare the different effects of high-intensity interval training and moderate-intensity continuous training by equalizing training load. DESIGN: Randomized controlled trial. METHODS: First intervention, 30 volunteers were randomized into low-intensity continuous training group or sedentary group. The low-intensity continuous training group was assigned to a 12-week training program at an intensity of 40% maximum heart reserve. The second intervention was an 8-week training program, in which 18 individuals were randomly placed either in the moderate-intensity continuous training or high-intensity interval training group. Flow-mediated dilatation, blood samples, carotid ultrasound, and wall shear stress were collected before, during, and after the interventions. RESULTS: Flow-mediated dilatation was significantly increased in low-intensity continuous training group (p = 0.02), moderate-intensity continuous training (p = 0.023) and high-intensity interval training (p < 0.01) groups, with a time × group interaction for %FMD (F2, 32 = 4.421, p = 0.02), and a main effect of time (F2, 32 = 27.658, p < 0.001). Nitric oxide in low-intensity continuous training increased remarkably (p = 0.024) and was higher than that in control (p = 0.011). High-intensity interval training (p < 0.001) and moderate-intensity continuous training (p < 0.001) increased nitric oxide. Endothelin was decreased only in high-intensity interval training group (p = 0.049). All the training programs had a remarkable impact on wall shear stress. CONCLUSIONS: Low-intensity continuous training can improve endothelial function in postmenopausal females. High-intensity interval training could be an effective training regimen for improving endothelial function than moderate-intensity continuous training in postmenopausal females.

Effects of Exercise on Inflammatory Cytokines in Patients with Type 2 Diabetes: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: Inflammation is involved in the pathogenesis of type 2 diabetes (T2DM) and the occurrence of insulin resistance. The purpose of this study was to investigate the effects of exercise on inflammatory factors in patients with T2DM. METHODS: A systematic review was conducted on five databases, Cochrane, Embase, Pubmed, Web of Science, and EBSCO. All randomized controlled trials (RCTs) published between establishment of the database and November 2020 without restrictions on language were included. Studies evaluated the effects of exercise intervention on inflammatory cytokines in patients with T2DM were selected. RESULTS: Twenty-three randomized controlled trials (1350 patients) were included in our meta-analysis. Exercise can significantly reduce the level of C-reactive protein (CRP) (MD: -0.79, 95% CI: -1.26 to -0.33, p = 0.0008), tumor necrosis factor-α (TNF-α) (MD: -2.33, 95% CI: -3.39 to -1.27, p < 0.0001), and interleukin-6 (IL-6) (MD: -0.42, 95% CI: -0.60 to -0.24, p < 0.0001) in T2DM patients. CONCLUSION: The findings of this review suggest that exercise reduces inflammatory cytokines (CRP, TNF-α, and IL-6) in T2DM patients. More studies with high methodological qualities and large sample sizes need to be done to confirm which forms of exercise are most effective.