Muscular and mitochondrial effects of long-term fluoxetine treatment in mice, combined with physical endurance exercise on treadmill.

AIM: Fluoxetine, one of the first newer SSRI antidepressant, is an extremely popular treatment for depression that could improve mental health problems. Many recent studies have suggested that SSRI have potential beneficial effects on skeletal muscle tissue. MAIN METHOD: We evaluated the potential beneficial effects of oral fluoxetine (18 mg/kg/day for 6 weeks) on muscle performance, after 6 weeks of physical exercise on treadmill. Male mice were randomly assigned to four groups (n = 12 per group) for treatment. Each group received treatment with following specifications: 1) no exercise with vehicle treatment (SED-S); 2) no exercise with fluoxetine treatment (SED-F); 3) exercise with vehicle treatment (EX-S); and 4) exercise with fluoxetine treatment (EX-F). Exercise performances were assessed based on the exhaustive running time and forelimb grip strength, anxious behavior by elevated plus-maze and open-field tests. Mitochondrial enzymes activity and ROS production were measured in the gastrocnemius and soleus muscles. KEY FINDING: Fluoxetine treatment had a significant effect on maximal aerobic capacity in mice without exercise, but more significant effects on gripping strength and anxiety when combined with exercise training, e.g. increased strength and decreased anxiety. SIGNIFICANCE: Fluoxetine treatment and exercise stimulation also had synergistic effects on strength and increased mitochondrial activity, cellular oxidative and antioxidant capacity in two different muscles.

Electrochemical Skin Conductance as a Marker of Painful Oxaliplatin-Induced Peripheral Neuropathy.

PURPOSE: Oxaliplatin is a platinum compound widely used in gastrointestinal cancer treatment but produces dose-limiting peripheral neuropathy. New insights into oxaliplatin-induced peripheral neuropathy (OIPN) assessment are needed to detect more effectively this condition. In this context, we conducted Canaloxa study, a prospective preliminary clinical trial that aimed to investigate how Electrochemical Skin Conductance (ESC), a parameter used in small fiber neuropathy assessment, could be helpful in OIPN diagnosis. METHODS: Cancer patients treated for at least three months with oxaliplatin and suffering from clinically OIPN were included. Electrochemical Skin Conductance, thermal thresholds, and neuropathic pain were assessed in all included patients. RESULTS: During one year, 36 patients were included. The main result was the correlation between ESC and Neuropathic Pain Symptom Inventory score for hands (rho value = -0.69, p < 0.0001) and feet (rho value = -0.79, p < 0.0001). ESC values were lower in neuropathic patients with painful symptoms than in ones without painful symptoms (p = 0.0003 and p < 0.0001 for hands and feet, respectively). No correlation was observed between ESC and thermal thresholds. CONCLUSION: These preliminary data suggest that ESC could be a useful objective marker of painful oxaliplatin-induced neuropathy and could complement the use of subjective clinical scales. This study was prospectively registered on clinicaltrials.gov (NCT02827916) before patient recruitment has begun.

Induction of brain Nrf2-HO-1 pathway and antinociception after different physical training paradigms in mice.

AIM: Activation of the Nrf2-antioxidant response element signaling pathway is a major mechanism in the cellular defense against oxidative or electrophilic stress through conjugative reactions and by enhancing cellular antioxidant capacity. Although exercise training up-regulates antioxidant defenses system, while information regarding the intensity levels of physical exercise that acts on the cellular protection systems is limited. MAIN METHODS: The present study evaluated the effects of different durations and intensities of physical exercise on the hippocampus, cortex and hypothalamus Nrf2 and HO-1 gene expression and related protein content and the nociception thresholds in adult C57Bl male mice. Exercise training consisted of daily running on a 10-lane rodent motor-driven treadmill for either 3 or 7 weeks at three different intensities. Pain responses were evaluated after exercise and in untrained mice by Von Frey hair test and cold plate test. KEY FINDINGS: This study confirmed that only vigorous and longer duration aerobic exercise increased Nrf2 protein level in the hippocampus and HO-1 protein level in the cortex and reduced pain perception. Mechanical and thermal hypoalgesia were only observed in exercise groups after 7 weeks of physical training. SIGNIFICANCE: The overall findings in this study confirm that only the long duration intensive forced exercise reduced inflammatory pain by induction of Nrf2/HO-1 antioxidant signaling pathway.