Physical exercise is a low-cost, safe, and efficient intervention for the reduction of neuropathic chronic pain in humans. However, the underlying mechanisms for how exercise reduces neuropathic pain are not yet well understood. Central monoaminergic systems play a critical role in endogenous analgesia leading us to hypothesize that the analgesic effect of low-intensity exercise occurs through activation of monoaminergic neurotransmission in descending inhibitory systems. To test this hypothesis, we induced peripheral nerve injury (PNI) by crushing the sciatic nerve. The exercise intervention consisted of low-intensity treadmill running for 2 weeks immediately after injury. Animals with PNI showed an increase in pain-like behaviors that were reduced by treadmill running. Reduction of serotonin (5-hydroxytryptamine) synthesis using the tryptophan hydroxylase inhibitor para-chlorophenylalanine methyl ester prevented the analgesic effect of exercise. However, blockade catecholamine synthesis with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine had no effect. In parallel, 2 weeks of exercise increased brainstem levels of the 5-HT and its metabolites (5-hydroxyindoleacetic acid), decreased expression of the serotonin transporter, and increased expression of 5-HT receptors (5HT-1B, 2A, 2C). Finally, PNI-induced increase in inflammatory cytokines, tumor necrosis factor-alpha, and interleukin-1 beta, in the brainstem, was reversed by 2 weeks of exercise. These findings provide new evidence indicating that low-intensity aerobic treadmill exercise suppresses pain-like behaviors in animals with neuropathic pain by enhancing brainstem 5-HT neurotransmission. These data provide a rationale for the analgesia produced by exercise to provide an alternative approach to the treatment of chronic neuropathic pain.

Objective : Motor Imagery (MI)-based Brain-Computer Interfaces (BCIs) have been proposed for the rehabilitation of people with disabilities, being a big challenge their successful application to restore motor functions in individuals with Spinal Cord Injury (SCI). This work proposes an Electroencephalography (EEG) gait imagery-based BCI to promote motor recovery on the Lokomat platform, in order to allow a clinical intervention by acting simultaneously on both central and peripheral nervous mechanisms. Methods: As a novelty, our BCI system accurately discriminates gait imagery tasks during walking and further provides a multi-channel EEG-based Visual Neurofeedback (VNFB) linked to $\mu$ (8-12 Hz) and $\beta$ (15-20 Hz) rhythms around Cz. VNFB is carried out through a cluster analysis strategy-based Euclidean distance, where the weighted mean MI feature vector is used as a reference to teach individuals with SCI to modulate their cortical rhythms. Results : The developed BCI reached an average classification accuracy of 74.4%. In addition, feature analysis demonstrated a reduction in cluster variance after several sessions, whereas metrics associated with self-modulation indicated a greater distance between both classes: passive walking with gait MI and passive walking without MI. Conclusion : The results suggest that intervention with a gait MI-based BCI with VNFB may allow the individuals to appropriately modulate their rhythms of interest around Cz. Significance: This work contributes to the development of advanced systems for gait rehabilitation by integrating Machine Learning and neurofeedback techniques, to restore lower-limb functions of SCI individuals.

Electrical stimulation is often used to treat weakness in people with spinal cord injury (SCI), however its efficacy to increase strength and trophism are weak and the mechanisms underlying the therapeutic benefits are unknown. The purpose of the 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. This was an experimental study. 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-weeks NMES protocol consisted in brachii biceps muscle stimulation, 5-times/week, initiated 48h after injury. Forepaw function and strength, biceps muscle trophism, and analysis of the phosphorylated Akt, p70S6K and GSK-3ß cellular anabolic pathway markers in stimulated muscle tissue were assessed. There was an increase in bicep muscle strength in the NMES group when compared with the untreated SCI group, from the 21^st postoperative day until the end of the evaluation period (p<0.05). Also, there was an increase in muscle trophism in the NMES group when compared to the SCI group (p = 0.005). Forelimb function gradually recovered in both the SCI and NMES groups, with no differences between them. Regarding muscle protein expression, the NMES group had higher values for phospho-Akt (p = 0.047), phospho-p70S6K (p = 0.029) and phospho-GSK-3ß (p = 0.018) compared to the SCI group. These experimental findings were limited to an incomplete-SCI animal model and may not be fully generalizable to humans. 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.