Distinct effects of thermal treatments after lengthening contraction on mechanical hyperalgesia and exercise-induced physiological changes in rat muscle

Delayed-onset muscle soreness (DOMS) is a common but displeasing event induced by excessive muscle use or unaccustomed exercise and characterized by tenderness and movement-related pain in the exercised muscle. Thermal therapies, either icing or heating applied to muscles immediately after exercise, have been used as therapeutic interventions for DOMS. However, the mechanisms of their analgesic effects, and physiological and metabolic changes in the muscle during thermal therapy, remain unclear. In the present study, we investigated the effects of both thermal treatments on mechanical hyperalgesia of DOMS and physiological and muscle metabolite changes using the rat DOMS model induced by lengthening contraction (LC) to the gastrocnemius muscle. Heating treatment just after LC induced analgesic effects, while rats with icing treatment showed mechanical hyperalgesia similar to that of the LC group. Furthermore, increased physiological responses (e.g., muscle temperature and blood flow) following the LC were significantly kept high only in the rats with heating treatment. In addition, heating treatment increased metabolites involved in the improvement of blood flow and oxidative metabolisms in the exercised muscle. The results indicated that heating treatment just after LC has analgesic effects on DOMS, which might be mediated partly through the improvement of muscle oxidative metabolisms by changes in metabolites and elevated physiological responses. NEW & NOTEWORTHY Physiological effects of thermal therapy in the muscle and its mechanisms of analgesic effects remain unclear. The results indicated that heating, but not icing, treatment just after lengthening contractions induced analgesic effects in the rat muscle. Increases in hemodynamics, muscle temperature, and metabolites such as nicotinamide were more prominent in heating treatment, consistent with improvement of muscle oxidative metabolisms, which might reduce chemical factors to induce mechanical hyperalgesia.

Inhibition of calpain prevents muscle weakness and disruption of sarcomere structure during hindlimb suspension

Unloading skeletal muscle results in atrophy and weakness. Inhibition of calpain activity during unloading reduced atrophy, but the impact on force generation has not been determined. Our hypothesis was that inhibition of calpain, through muscle-specific overexpression of calpastatin, would prevent the disruption of sarcomere structure and decreased specific force (kN/m2) observed during unloading. Calpastatin-overexpressing ( cp) and wild-type ( wt) mice were subjected to 3, 9, or 14 days of hindlimb suspension (HS). Compared with soleus muscles of non-suspended control mice, soleus muscles of wt mice showed a 25% decline in mass after 14 days of HS while maximum isometric force (Po) decreased by 40%, resulting in a specific Po that was 35% lower than control values. Over the same time period, muscles of cp mice demonstrated 25% declines in both mass and Po but no change in specific Po. Consistent with the preservation of specific force during HS, soleus muscles of cp mice also maintained a high degree of order in sarcomere structure, in contrast to wt muscles that demonstrated misalignment of z-lines and decreased uniformity of thick filament lengths. Susceptibility to lengthening contraction-induced injury increased with the duration of HS and was not different for muscles of cp and wt mice. We conclude that inhibition of calpain activity during unloading preserves sarcomere structure such that the isometric force-generating capability is not diminished, while the effects of unloading on lengthening contraction-induced injury likely occur through calpain-independent mechanisms.

Neutrophil accumulation following passive stretches contributes to adaptations that reduce contraction-induced skeletal muscle injury in mice

Skeletal muscles can be injured by their own contractions, especially when the muscle is stretched during a lengthening contraction. Exposing a muscle to a conditioning protocol of stretches without activation (passive stretches) before lengthening contractions reduces contraction-induced injury. Although passive stretching does not damage muscle fibers, neutrophils are elevated in the muscle after passive stretches. Our purpose was to investigate the relationship between neutrophil accumulation following passive stretches and the protection from subsequent contraction-induced injury provided by the passive stretches. Our hypothesis was that passive stretch conditioning would not provide protection from subsequent lengthening contraction-induced injury under circumstances when the increase in muscle neutrophils in response to the conditioning was prevented. Extensor digitorum longus muscles of mice were conditioned with passive stretches 14 days before exposure to a protocol of damaging lengthening contractions. Mice were either untreated or treated with an antibody (RB6-8C5) that reduced the level of circulating neutrophils by over 95% before administration of passive stretches. Neutrophil levels recovered in treated mice by the time lengthening contractions were performed. Lengthening contractions were also administered to muscles with no prior exposure to passive stretches. Maximum isometric force, number of damaged fibers, and muscle neutrophil concentration were measured 3 days after lengthening contractions. Compared with nonconditioned control muscles, the severity of contraction-induced injury was not reduced by prior passive stretch conditioning when mice were treated with RB6-8C5 before conditioning. We conclude that neutrophils contribute to adaptations that protect muscles from injury.