Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano-and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle

International audienceThe aim of the present study was to investigate long term effects of motor denervation by botulinum toxin complex type A (BoNT/A) from Clostridium Botulinum, on the afferent fibers originating from the gastrocnemius muscle of rats. Animals were divided in 2 experimental groups: 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle, the latter being itself divided into 3 subgroups according to their locomotor recovery with the help of a test based on footprint measurements of walking rats: i) no recovery (B0), ii) 50% recovery (B50) and iii) full recovery (B100). Then, muscle properties , metabosensitive afferent fiber responses to potassium chloride (KCl) and lactic acid injections and Electrically-Induced Fatigue (EIF), and mechanosensitive responses to tendon vibrations were measured. At the end of the experiment, rats were killed and the toxin injected muscles were weighted. After toxin injection, we observed a complete paralysis associated to a loss of force to muscle stimulation and a significant muscle atrophy, and a return to baseline when the animals recover. The response to fatigue was only decreased in the B0 group. The responses to KCl injections were only altered in the B100 groups while responses to lactic acid were altered in the 3 injected groups. Finally, our results indicated that neurotoxin altered the biphasic pattern of response of the mechanosensitive fiber to tendon vibrations in the B0 and B50 groups. These results indicated that neurotoxin injection induces muscle afferent activity alterations that persist and even worsen when the muscle has recovered his motor activity

Morton's neuroma

Morton neuroma is a perineural fibrosis and nerve degeneration of the common digital nerve occurring most frequently between the 3rd and 4th metatarsal heads. Morton's neuroma induces violent and sporadic pain. The entrapped and damaged nerve causes aching and burning of the forefoot. Women are more affected than men. The symptoms of Morton's disease are aggravated by wearing shoes that are too tight or narrow in the forefoot. When conservative treatments are unsuccessful (orthoses, injections), surgery may be considered

[Role of metabosensitive afferent fibers in neuromuscular adaptive mechanisms]

International audienceRole of metabosensitive afferent fibers in neuromuscular adaptive mechanisms. Adaptation to exercise is provided by central neuron activity adjustments which are regulated partly by activation of group I and II (mechanosensitive) and group III and IV (metabosentitive) afferent fibers. These last two groups are activated by exercise-induced changes in muscle metabolism. The role played by these afferents seems to be crucial to exercise and fatigue tolerance adaptive mechanisms. Nevertheless, many questions remain unresolved. The aim of this review is to focus on the involvement of metabosensitivity in sensorimotor loops and neuromuscular adaptive mechanisms. The existence of an adaptive cardiovascular and respiratory reflex to exercise originating from metabosensitive afferent fiber activation is well established. Furthermore, the mechanism of skeletal muscle protection against fatigue could be due to modulation of central motor command at the spinal and supraspinal levels via these afferent fibers

[Role of metabosensitive afferent fibers in neuromuscular adaptive mechanisms]

International audienceRole of metabosensitive afferent fibers in neuromuscular adaptive mechanisms. Adaptation to exercise is provided by central neuron activity adjustments which are regulated partly by activation of group I and II (mechanosensitive) and group III and IV (metabosentitive) afferent fibers. These last two groups are activated by exercise-induced changes in muscle metabolism. The role played by these afferents seems to be crucial to exercise and fatigue tolerance adaptive mechanisms. Nevertheless, many questions remain unresolved. The aim of this review is to focus on the involvement of metabosensitivity in sensorimotor loops and neuromuscular adaptive mechanisms. The existence of an adaptive cardiovascular and respiratory reflex to exercise originating from metabosensitive afferent fiber activation is well established. Furthermore, the mechanism of skeletal muscle protection against fatigue could be due to modulation of central motor command at the spinal and supraspinal levels via these afferent fibers

Etude de la régénération nerveuse périphérique post-traumatique avec perte de substance chez les rats (mise au point et évaluation de procédés de guidage implantables et stratégies pharmacologiques)

[ ] Ces stratégies visent à être complémentaires, dans l optique d une thérapie alternative à l autogreffe. Nos résultats ont montré pour la première fois que le FK506 et la vitamine D favorisent la myélinisation et la maturation physiologique des fibres nerveuses périphériques axotomisées. De plus, la vitamine D augmente l axogenèse, la récupération fonctionnelle des fibres nerveuses métabosensitives et diminue la perte axonale. Concernant les matériaux implantables, nous montrons que les tuteurs nerveux limitent la perte axonale. De plus, ce type de guide entraîne des récupérations fonctionnelles identiques à l autogreffe. Toutefois, le muscle squelettique dénaturé reste insatisfaisant. Ces résultats démontrent que le tuteur nerveux collagénique que nous avons mis au point constitue une alternaticve efficace à l'autogreffe nerveuse. Parralèlement, la vitamine D possède des propriètés de neuroprotection et de neurorégénération qui permettraient, en association avec l'implantation du tuteur, d'envisager des récupérations au-delà des valeurs de l'autogreffe. D'autres études sont envisagées mettant en jeu l'intégration d'une matrice de guidage au sein du tuteur.[ ] We show here that the collagen nerve guide 1) limits the axonal loss an 2) induces a functional recovery in a similar way to the ANG. Conversely, the denatured skeletal muscle cannot be considered as a relevant alternative. With respect to our tested pharmacological compounds, we show here that both FK506 and vitamin D promote myelination and physiological maturation of axotomized peripheral nerve fibers. On the one hand, vitamin D signicantly 1) increases axogenesis and functional recovery of metabosensitive nerve fibers and 2) reduces axon degeneration. On the other hand, FK506 potentiates functional recovery of metabosensitive fibers. We can conclude that the collagen nerve guide used in this study is an alternative to ANG technique. However, further studies are warranted ti improve the collagen conduit. We plant to insert a guidance matrix into the guide. in order to avoid confounding factors, physical and pharmacological strategies were assessed separately. In the future, they could be combined with the aim of achieving a more complete structural and functional recovery.AIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocSudocFranceF

Modulation of the spinal excitability by muscle metabosensitive afferent fibers

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Respiratory and cardiovascular responses evoked by tibialis anterior muscle afferent fibers in rats

International audienceno abstrac

Does metabosensitive afferent fibers activity differ from slow- and fast-twitch muscles?

International audienceThis study was designed to investigate the metabosensitive afferent response evoked by electrically induced fatigue (EIF), lactic acid (LA) and potassium chloride (KCl) in three muscle types. We recorded the activity of groups III-IV afferents originating from soleus, gastrocnemius and tibialis anterior muscles. Our data showed a same pattern of response in the three muscles after chemical injections, i.e., a bell curve with maximal discharge rate at 1 mM for LA injections and a linear relationship between KCl concentrations and the afferent discharge rate. Furthermore, a stronger response was recorded after EIF in the gastrocnemius muscle compared to the two other muscles. The change in afferent discharge after 1 mM LA injection was higher for the gastrocnemius muscle compared to the response obtained with the corresponding concentration applied in the two other muscles, whereas changes to KCl injections did not dramatically differ between the three muscles. We conclude that anatomical (mass, phenotype, vascularization, receptor and afferent densityaEuro broken vertical bar) and functional (flexor vs. extensor) differences between muscles could explain the amplitude of these responses

Alteration of Metabosensitive Afferent Response With Aging: Exercised versus Non-exercised Rats

International audienceThis study was designed to evaluate the effect of aging on the activity of metabosensitive afferent fibers (thin muscle afferents from group III and IV) and to determine if physical activity performed at old age may influence the afferent discharge. Afferents from tibialis anterior and soleus muscles were recorded on non-exercised rats aged of 3, 6, 12, and 20 months and on animals aged of 12 and 20 months performing a daily incremental treadmill exercise protocol during the last 8 weeks preceding the recordings. Metabosensitive afferent fibers were activated with potassium chloride (KCl) and lactic acid (LA) injections into the blood stream or by muscle electrically-induced fatigue (EIF). Results indicated that aging is associated to a decrease in the magnitude of the responses to chemical injections and EIF. Unfortunately, physical activity did not allow restoring the metabosensitive afferents responses. These results indicate an alteration of the thin afferent fibers with aging and should be taken into account regarding the management of muscle fatigue and potential alterations of exercise pressor reflex (EPR) occurring with aging

Restoration of post-activation depression of the H-reflex by treadmill exercise in aged rats

International audienceThe purpose of this study was to evaluate the effects of aging and chronic physical activity on the post-activation depression of the Hoffman reflex (H-reflex). The maximal amplitude H wave/maximal amplitude M wave ratio was measured, and the rate-sensitive depression of the H-reflex was assessed. Measurements were performed on sedentary rats aged of 3, 6,12, and 20 months and on animals aged of 12 and 20 months performing an incremental treadmill exercise protocol during the last eight weeks preceding the recordings. At the end of the experiment, the muscle mass and/or body mass ratio was calculated. Results indicated that the H-reflex depression of the tibialis anterior and soleus muscles were present until age of 6 and 12 months, respectively. For the tibialis anterior muscle, results also pointed out a decrease in the relative muscle mass with age and that the exercise allowed to restore the rate-sensitive depression of the H-reflex and to increase the relative muscle mass in comparison with sedentary animals. These findings clearly demonstrate that neural alteration of the spinal cord is prevented by activity in aged rats. (C) 2016 Elsevier Inc. All rights reserved