Soft-Tissue Pathomechanics - Fundamentals and Assessment Tools for Occupational Ergonomics - page 363

15.5.1 Strain Injuries and Skeletal Muscle
Strain injuries are the result of three basic processes: (1) Initially, excessive forces coupled with lengthen-
ing result in structural damage to muscle cells (myofibers), including tearing of the cell membrane
(i.e., the sarcolemma). (2) Structural damage to the sarcolemma results in an increase in intracellular
Ca 2þ levels, modifications of myofiber proteins and lipids, and the activation of intracellular pathways
that regulate the injured muscle's response to damage. (3) Pro- and anti-inflammatory factors (i.e.,
cytokines and chemokines) are released by local tissues and infiltrating immune cells. Cytokines and
chemokines cause inflammation and stimulate cellular pathways mediating muscle regeneration and
repair. These three processes are involved in mediating the extent of physical damage, functional
changes of the muscle, pain, and repair.
15.5.2 Physical Damage to Tissue
Strain injuries are caused by exposure of muscle and other soft tissues, including vasculature, nerves, and
tendons to excessive strain or lengthening. 86,89,165 Studies performed in both humans, 88,90,91,187,190 and
animals 10,161,257 have demonstrated that exposure to lengthening contractions results in physical damage
to muscle tissue that can include shearing of myofibers, the loss of intermediate filaments and mitochon-
dria, damage to the extracellular membrane, and disruptions in Z-line alignment (i.e., Z-line streaming).
Immunostaining for structural proteins that maintain the integrity of the myofiber, such as desmin,
titin, and fibronectin, have demonstrated that there are disruptions of the exo- and endosarcomeric
membranes, 86,163,164 and of the extracellular matrix 163,257 in strain-injured muscle tissue. In lengthening
contraction-induced injuries, damage within the muscle is most often seen at the myotendinous junction
and at specific sarcomeres. 95,114,192,201 In fact, it has been hypothesized that there is a population of sar-
comeres that are weaker, and tear more easily under lengthening conditions. 86,183,265 The stretch-induced
damage to the extracellular matrix, sarcomeres, and critical cell organelles is associated with reduced
isometric muscle force, 62,96,286,289 but not with pain. It has been hypothesized that these initial structural
changes initiate a chain of events that may maintain an injury-induced force deficit, result in inflam-
mation and pain, and stimulate pathways important for regulating muscle repair and regeneration.
15.5.3 Intracellular Ca 2 1 and Muscle Damage
Studies examining the effects of lengthening contractions on myofibers have demonstrated that there
is an influx of Ca 2þ into muscle cells 131,287,290 and mitochondria 66,267 in muscle exposed to damaging
contractions. Calcium influx into myofibers can be increased in two ways. First, extreme stretch and
strain can open the stretch-sensitive Ca 2þ channels in the cell membrane. However, treating animals
with a calcium channel blocker (i.e., verapamil) prior to injury only partially reduces the calcium
influx into the cell, 9 and therefore, Ca 2þ must be entering via an additional pathway. Injury-induced
tears and damage to the sarcolemma can also allow Ca 2þ to leak into the cell from the extracellular
fluid. 290 In in vitro studies, membrane damage, and enzyme efflux can be prevented in muscle exposed
to contractions by removing Ca 2þ from the extracellular buffer. 135 Treating animals with Ca 2þ chelators
(molecules that preferentially bind Ca 2þ and prevent it from entering the cell) during and after treadmill
running also reduces tissue damage and the influx of Ca 2þ in myofibers (66). Thus, this early influx of
Ca 2þ appears to play a critical role in mediating contraction-induced injuries to muscle tissue.
Increases in free Ca 2þ within myofibers can result in the degradation of myofiber proteins and lipids,
and result in the degeneration of damaged myofibers. 42 As mentioned earlier, intracellular Ca 2þ homeo-
stasis within myofibers is maintained by the SR. As intracellular Ca 2þ levels rise, the SR normally
increases the rate of Ca 2þ uptake to keep free intracellular concentrations fairly stable. However, it has
been demonstrated that the SR is less capable of sequestering additional Ca 2þ after muscle has been
exposed to lengthening contractions. 42 This reduction in Ca 2þ up- take by the SR is associated with a
reduction in muscle force 282 and may contribute to the rise in free intracellular Ca 2þ after injury-
inducing contractions. 42 Thus, the damage-induced loss of Ca 2þ homeostasis in injured myofibers