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focus on the effects of disuse. We do, however, investigate a number of questions: Is there evidence that tissue damage occurs at levels below the strength of the tissue? Is there evidence for microtrauma or damage accumulation? If so, what is the dose-response relationship? What are the mechanisms of injury and repair? How are the responses of tissues to load modified by intrinsic factors (e.g., age, gender)? Do existing studies support or refute an association between repeated loading and injury?

For the purposes of this chapter, several terms are defined. Elastic materials are those that regain their original shape after a load is removed. For such materials, the change in shape (e.g., strain) is proportional to the applied load (within certain limits). The constant of proportionality is called the stiffness. The force (e.g., stress) necessary to cause rupture or fracture is called the strength. In some cases, cyclically applied forces that are below the tissue strength may cause rupture or fracture via damage accumulation. This is called fatigue. Tissue fatigue can also lead to changes in other mechanical properties, such as reduced tissue stiffness.

Since pain is a common and important endpoint for humans with musculoskeletal disorders, this chapter begins with a review of the pain pathways from musculoskeletal tissues to the brain. This is followed by reviews of the biological responses of six tissues—vertebral bone, spinal disc, tendon and ligament, muscle, peripheral nerve, and spinal nerve root—to loading. These reviews are based on systematic evaluations of the scientific literature. The chapter summary integrates the findings across all tissues and draws conclusions about current knowledge of injury mechanisms. We conclude with suggestions for future research directions.


Evolution has provided our bodies with many senses by which to interact with the environment. Each sense (smell, vision, hearing, taste, and somatic sensibilities) has a highly specialized neural pathway. Pain is one of the somatic sensibilities (others are touch, temperature sensation, and proprioception) and itself has its own highly specialized set of neural pathways.

This specialization begins in the peripheral tissues. “Nociceptor” is the term given to the specialized receptors that serve as injury (or noxious stimuli) detectors. Activation of nociceptors evokes pain. Pain arouses us to protect the injured or threatened body part and hence plays a crucial role in survival. Nociceptors innervate a variety of tissues in ways that are appropriate from a teleological perspective. Lightly touching the cornea can injure the eye, and so the nociceptors that serve the cornea are quite sensitive to mechanical stimuli. The skin is a more resilient tissue, and

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