Skeletal muscle is composed primarily of contractile proteins (myosin and actin), regulatory proteins (tropomyosin and troponin), and a connective tissue matrix (13).

The muscle fiber is the basic structural element of skeletal muscle. Muscle is a syncytium of multinucleated fibers (17). The functional unit of muscle is the sarcomere. Within each sarcomere are light and dark bands. The dark bands are made up of both the thick myosin and thin actin filaments, whereas the light bands are made up of just the thin actin filaments that connect to the Z lines.

A muscle fiber originates via a tendon from bone, traverses one or more joints, and joins with a tendon that inserts to bone. Fiber arrangement can be parallel or oblique (unipennate, bipennate, multipennate) in orientation. Fibers can be classified as Type I (slow-twitch oxidative) and Type II (fast-twitch). Type II fibers are further classified into Type II (fast-twitch oxidative glycolytic) and Type IIb (fast-twitch glycolytic).

Satellite cells are separate cells along the periphery of the muscle fiber that are important in cellular regeneration in response to injury. Satellite cells proliferate and transform into myotubes in response to growth factors and cytokines that mediate the repair process (62).

The musculotendinous junction is a specialized region of highly folded membranes that increase the surface area for force transmission (13). Most muscle strain injuries occur in this region.

The sarcoplasmic reticulum is a specialized cellular organelle that is responsible for calcium movement across the cell membrane and electrical transmission within the cell.

A motor unit is a motor neuron and all the muscle fibers it innervates. The motor neuron innervates each of its muscle fibers at a motor end plate. The number of myofibers in a motor unit and the number of motor units in a skeletal muscle are determined by the function of the muscle (20). The fewer the fibers in a motor unit, the finer is the control (e.g., ocular muscles), whereas many fibers in a motor unit lead to gross movements (e.g., quadriceps).

A muscle contraction begins when an electrical impulse travels down a motor neuron’s axon to its motor end plates. This electrical impulse triggers the release of acetylcholine that migrates to receptors on the myofiber and causes a depolarization of the sarcolemma. The depolarization travels deep into the muscle by the transverse tubule, triggering the release of calcium from the sarcoplasmic reticulum. Calcium binds to troponin, which results in a conformational change in the tropomyosin, opening actin’s active site and allowing the crossbridges of the myosin head to interact. The crossbridges then undergo their own conformational change that pulls the thin actin filament to slide past the myosin toward the center of the sarcomere. The process of sarcolemmal depolarization and the resulting sliding of the filaments is referred to as excitation-contraction coupling. The physical process of muscle contraction is the sliding of the actin filament past the myosin filament toward the center of the sarcomere pulling the ends of the sarcomere (the Z lines) toward each other. The whole muscle shortens when the process is multiplied over thousands of sarcomeres, thousands of conformational changes at the myosin crossbridge heads, and all of the activated fibers. This process is powered by the hydrolysis of adenosine triphosphate (ATP) to both bind and break the connection of the crossbridge with the actin filament (17,20).

Muscle contraction can be isometric, concentric, or eccentric. Isometric contraction is when the force by the muscle is equal to the load, and although there is no visible joint movement, the muscle does shorten. By recruiting more muscle fibers to overcome the external load, a concentric (or shortening) contraction can occur, and there is visible joint movement. Eccentric contraction is when the external load is greater than the force generated by the muscle and the muscle lengthens (20). For example, raising the weight in an
arm curl is a concentric contraction of the elbow flexors, and lowering the weight is an eccentric contraction of the same flexors. Isometric strength measurements are strongly predictive of functional capacity and are sensitive in detecting changes in muscle strength (36).

The pathophysiology of the healing muscle is similar regardless of the type of injury. Healing occurs in three distinct phases: (a) degeneration and inflammation; (b) muscle regeneration; (c) development of fibrosis (20). The reparative process involves both inflammatory cells (neutrophils, macrophages) and myogenic (satellite) cells.

Acute hemorrhage and inflammatory cell infiltration of the damaged muscle tissue occurs shortly after injury (40).

Satellite cells are myogenic mononuclear cells responsible for muscle fiber repair and regeneration processes. They are located beneath the basal lamina of skeletal muscle fibers. Mechanical or chemical insults stimulate quiescent satellite cells through hepatocyte growth factor (HGF)/nitric oxide radical-dependent pathways (3,53). The activated satellite cells enter the cycle cell and differentiate into myoblasts, which fuse together and develop into multinucleated muscle fibers. Typically, these repaired myofibers attach to the extracellular matrix of the newly formed scar (32).

Fibroblast proliferation and collagen matrix synthesis occur along with the inflammatory response and muscle regeneration. This connective tissue scar formation may inhibit the complete repair of injured muscle (32). Muscle degeneration and inflammation occur during the first days after injury. Regeneration then starts after 1 week, peaks at 2 weeks, and is typically complete by 3-4 weeks. Scar tissue starts to form 2-3 weeks after injury and increases (18).

There has been considerable muscle-derived stem cell (MDSC) research recently, and the literature provides evidence that stem cells participate in myofiber regeneration. In addition, these pluripotent stem cells can differentiate into endothelial and neural lineages, which may be beneficial in vascular and neural supply to the regenerating muscle. MDSCs have also been used to produce proregenerative and antifibrotic agents (18). However, the medical evidence in humans is limited, and further studies are needed.

Muscle strain is the most common injury sustained in sports. Muscle can be functionally limited from delayed muscle soreness (discussed later), partial muscle strain, or complete muscle disruption.

A common feature in muscle tissue injury is muscle stretch in combination with a strong contraction in two-joint muscles (e.g., rectus femoris, biceps femoris, gastrocnemius) or muscles with a complex architecture (e.g., adductor longus). The injury occurs when selected muscles restrict range of motion of the joint they cross and a significant amount of tension is placed on that muscle (40).

Clinically, muscle injury (strain/contusion) is classified depending on the level of damage generated: mild when the loss of strength and movement is minimal or nonexistent, moderate with inability to contract, and severe for absolute loss of function (22).