High-intensity swimming exercise reduces inflammatory pain in mice by activation of the endocannabinoid system.

As exercise intervention solely for pain reduction is relatively new, the available research still leaves an incomplete picture of responsible mechanisms and pathways. Nonetheless, evidence indicates that exercise-induced analgesia involves activation of the endocannabinoid (eCB) system. The present study investigated the role of the eCB system on the antihyperalgesic effect of high-intensity swimming exercise (HISE) in an animal model of peripheral persistent inflammation. Male Swiss mice were allocated to non-exercised and exercised groups and subjected to subcutaneous intraplantar injection (i.pl.) of a single dose of complete Freund's adjuvant (CFA) to induce inflammatory pain. Cumulative HISE was performed once a day, and mechanical hyperalgesia and edema were evaluated 0.5 hour after HISE for seven consecutive days. To investigate the role of the eCB system on the antihyperalgesic effect of HISE, non-exercised and exercised mice received intraperitoneal (ip), intrathecal (i.t.) or i.pl. injections of vehicle, AM281 (a CB1 cannabinoid receptor antagonist) or AM630 (a CB2 cannabinoid receptor antagonist) from the 3rd to 5th day after CFA injection. Mechanical hyperalgesia was evaluated 0.5 hour after HISE. In addition, the effect of the fatty acid amide hydrolase [FAAH] inhibitor or monoacylglycerol lipase [MAGL] inhibitor on the antihyperalgesic action of HISE was investigated. HISE reduced mechanical hyperalgesia with effects prevented by AM281 or AM630 pretreatment in all delivery routes tested. The inhibition of FAAH and MAGL prolonged the antihyperalgesic effect of HISE. These data demonstrate evidence for the role of the eCB system upon exercise-induced analgesia in a murine model of inflammatory pain.

Early Cyclical Neuromuscular Electrical Stimulation Improves Strength and Trophism by Akt Pathway Signaling in Partially Paralyzed Biceps Muscle After Spinal Cord Injury in Rats.

Background: Electrical stimulation is often used to treat weakness in people with spinal cord injury (SCI); however its efficacy for increasing strength and trophism is weak, and the mechanisms underlying the therapeutic benefits are unknown. Objective: The purpose of this study was to analyze the effects of neuromuscular electrical stimulation (NMES) on muscle function, trophism, and the Akt pathway signaling involved in muscular plasticity after incomplete SCI in rats. Design: This was an experimental study. Methods: Twenty-one adult female Wistar rats were divided into sham, SCI, and SCI plus NMES groups. In injured animals, SCI hemisection was induced by a surgical procedure at the C5-C7 level. The 5-week NMES protocol consisted of biceps brachii muscle stimulation 5 times per week, initiated 48 h after injury. Forepaw function and strength, biceps muscle trophism, and the expression of phosphorylated Akt, p70S6K, and GSK-3ß cellular anabolic pathway markers in stimulated muscle tissue were assessed. Results: There was an increase in bicep muscle strength in the NMES group compared with the untreated SCI group, from postoperative day 21 until the end of the evaluation period. Also, there was an increase in muscle trophism in the NMES group compared with the SCI group. Forelimb function gradually recovered in both the SCI group and the NMES group, with no differences between them. Regarding muscle protein expression, the NMES group had higher values for phospho-Akt, phospho-p70S6K, and phospho-GSK-3ß than did the SCI group. Limitations: The experimental findings were limited to an animal model of incomplete SCI and may not be fully generalizable to humans. Conclusions: Early cyclical NMES therapy was shown to increase muscle strength and induce hypertrophy after incomplete SCI in a rat model, probably by increasing phospho-Akt, phospho-p70S6K, and phospho-GSK-3ß signaling protein synthesis.

Structure-activity relationship of flavonoids derived from medicinal plants in preventing methylmercury-induced mitochondrial dysfunction.

In the present study, we investigated the potential protective effects of three flavonoids (myricetin, myricitrin and rutin) derived from medicinal plants against methyl mercury (MeHg)-induced mitochondrial dysfunction in vitro. Incubation of mouse brain mitochondria with MeHg induced a significant decrease in mitochondrial function, which was correlated with decreased glutathione (GSH) levels and increased generation of reactive oxygen species (ROS) and lipid peroxidation. The co-incubation of mouse brain mitochondria with myricetin or myricitrin caused a concentration-dependent decrease of MeHg-induced mitochondrial dysfunction and oxidative stress. The flavonoid rutin was ineffective in counteracting MeHg toxicity. Among the three tested flavonoids, myricetin was the most efficient in protecting against MeHg-induced mitochondrial dysfunction. Moreover, myricetin completely blocked MeHg-induced ROS formation and lipid peroxidation and partially prevented MeHg-induced GSH depletion. The ability of myricetin to attenuate MeHg-induced mitochondrial dysfunction and oxidative stress appears to be related to its higher scavenging capability when compared to myricitrin and rutin. Overall, the results suggest that MeHg-induced mitotoxicity is associated with oxidative stress. The ability of myricetin to prevent MeHg-induced oxidative damage in brain mitochondria renders this flavonoid a promising molecule for further in vivo studies in the search for potential antidotes to counteract MeHg-induced neurotoxicity.

Thiophenes and furans derivatives: a new class of potential pharmacological agents.

A new class of potential pharmacological thiophenes and furans compounds has been prepared. The obtained thiophenes and furans derivatives were screened for anti-inflammatory, antinociceptive and antioxidant activity in rats. In vitro hepatic ALA-D activity was also evaluated. Thiophene 2 exhibited higher anti-inflammatory effect than thiophenes 1 and 3. However, compound 1 demonstrated lower IC(50) for lipid peroxidation than 2 and 3 in liver and brain. Furan compounds 4-6 presented similar anti-inflammatory activity. The acetylenic furans 4 and 5 inhibited scarcely lipid peroxidation at low concentration as 10 µM. Conversely, furan compound 6 was the most effective against lipid peroxidation in liver. Furans 4 and 5 inhibited lipid peroxidation, in brain, only in high concentrations. In contrast, furan 6 protected (90%) against lipid peroxidation at 10 µM. Thiophene 1 was devoid of anti-inflammatory activity but was efficient in reducing acetic acid-induced constriction. Conversely, it analogue furan 4 presented anti-inflammatory and antinociceptive activity. Thiophene and furan inhibited hepatic ALA-D only at high concentrations. All compounds displayed antioxidant activity however the anti-inflammatory activity is not related to antioxidant potential.