translation of fibrogenic proteins from their mRNA; (b) upregulated export of important extracellular matrix proteins, like collagen, from the endoplasmic reticulum to the extracellular matrix; and (c) a shift in the balance between extracellular matrix assembly and degradation to favor the assembly of extracellular matrix.
Risk factors/activities associated with muscle disorders
Repetitive work tasks are known risk factors for causing work‐related musculoskeletal chronic muscle pain and fatigue (Bongers et al., 2006; Larsson et al., 2007; Sjøgaard et al., 2000). In normal skeletal muscle, highly repetitive and high force work tasks can independently induce muscle inflammation and fibrosis, concomitant with muscle pain and weakness, with greater pathology when the two risk factors are combined (Barbe, Gallagher, Massicotte, et al., 2013b; Barbe, Gallagher, & Popoff, 2013a; Fisher et al., 2015; Hilliard et al., 2020). Exposure‐dependent fibrogenic changes have been observed in an operant rat model of work (repetitive reaching and grasping a varied load levels), with longer duration and higher repetitive and force demand tasks inducing greater tissue fibrosis than shorter or easier tasks, with evidence of inflammation at earlier time points and more fibrosis at later time points after inflammation has resolved (Barbe, Gallagher, Massicotte, et al., 2013b; Barbe, Gallagher, & Popoff, 2013a).
Nerve Disorders
Carpal tunnel syndrome (median nerve entrapment or irritation)
Characteristics/description
Carpal tunnel syndrome (CTS) is a hand and wrist disorder caused by nerve entrapment of the median nerve in the wrist (Figure 2.8). Symptoms resulting from the median nerve entrapment include pain, tingling, burning, or numbness in the thumb, index finger, middle finger, and the thumb side of the ring fingers (Burton, 2014). Symptoms generally begin slowly and often first become evident at night. Typical symptoms include numbness, tingling, pain, and/or a burning sensation in the affected regions. Initial symptoms may vary in intensity. However, as symptoms progress, they will often become more consistent and will occur during the daytime hours as well at night. Worsening symptoms may include pain and tingling symptoms radiating to the forearm and shoulder. As the syndrome gets worse, a loss of strength and coordination can be experienced, and many activities of daily living can be severely affected.
Epidemiology
CTS is the most common of all the nerve entrapment syndromes (Miller & Reinus, 2010). Estimates of the rate of CTS have been reported to range from 2.3 to 7.5 cases per 100 person‐years (Cardona et al., 2019). In a study of 4,321 primarily industrial workers, CTS was observed to afflict 7.8% of the cohort (Dale et al., 2013). Estimates of the prevalence of CTS are generally around 2% of the population (Descatha et al., 2010), with a lifetime incidence of approximately 10–15% (Miller & Reinus, 2010). The higher end of these incidence estimates is generally seen in those having significant occupational exposure (Palmer, Harris, & Coggon, 2007). Women generally exhibit 3–5 times greater incidence rates than men, and cases in women are typically seen between the ages of 30 and 60 years (Miller & Reinus, 2010). Pregnancy is a notable risk factor for CTS in females, thought to be due to increased pressure in the carpal tunnel due to swelling of the structures running through the canal from the additional water retention associated with pregnancy. Cases in men are usually seen between the ages of 35 and 40 years, and men’s CTS cases are often occupationally related (Palmer et al., 2007). Overall, the dominant hand is the most often affected; however, up to 50% of cases involve bilateral symptoms (Miller & Reinus, 2010).
Figure 2.8 Location of the carpal tunnel and path of the median nerve in the hand.
Medical treatment of CTS has been estimated to cost over $2 billion annually (Dale et al., 2013; Falkiner & Myers, 2002; Stapleton, 2006). Indirect costs such as lost work time and job change may be substantially greater (Faucett, Blanc, & Yelin, 2000; Foley, Silverstein, & Polissar, 2007). Exposure to physical risk factors such as high force, non‐neutral working postures, and repetition are well‐known risk factors for MSDs (da Costa & Vieira, 2010; National Research Council – Institute of Medicine, 2001; NIOSH, 1997). Recent evidence from a prospective study of 2,474 service and production workers suggests that interactions of these risk factors demonstrate a strong association with incident CTS (Harris‐Adamson et al., 2015).
Anatomy/pathology
The median nerve is one of the numerous structures passing through the carpal tunnel in the wrist. These include nine tendons (four flexor digitorum superficialis, four flexor digitorum profundus, and the flexor pollicis longus), various blood vessels, and the median nerve. The carpal tunnel is bounded superficially by the flexor retinaculum, has a deep border formed by palmar aspects of several carpal bones, is bounded laterally by the medial surface of the trapezium, and is bounded medially by the lateral surface of the hamate bone.
Various studies have provided findings which suggest that damage development to neural and tendinous tissues may be associated with symptom development (Barbe et al., 2020; Bove et al., 2019; Chikenji, Gingery, Zhao, Passe et al., 2014; Clark, Al‐Shatti, Barr, Amin, & Barbe, 2004; Clark et al., 2003; Elliott et al., 2009; Elliott, Barr, Clark, Wade, & Barbe, 2010; Ettema, Zhao, An, & Amadio, 2006; Jain et al., 2014). Studies that have biopsied tissues in CTS cases have suggested that the development of median nerve compression may be the consequence of connective tissues experiencing degeneration due to repeated mechanical stress (Festen‐Schrier & Amadio, 2018; Schrier, Vrieze, & Amadio, 2020; Schuind, Ventura, & Pasteels, 1990). Structures affected by repeated stress can include flexor tendons and their synovial sheath (Kerr, Sybert, & Albarracin, 1992). Degenerative noninflammatory fibrosis and thickening of the synovium have been implicated as a factor in median nerve pathology (Chikenji, Gingery, Zhao, Passe et al., 2014; Ettema et al., 2006; Sternbach, 1999). Tendon fibrosis changes may impact the gliding mechanism of the subsynovial connective tissue (SSCT), which moves en bloc with the tendons and median nerve (Ghasemi‐Rad et al., 2014). Increases in vascularity, fibroblast density, and collagen fiber size have been reported in resected synovial specimens and are also indicative of synovial degeneration (Jinrok et al., 2004). If a decrease in SSCT motion were to result from fibrosis, the movement of the tendons would likely increase shear strain in the SSCT (Ghasemi‐Rad et al., 2014). The degree of shear strain would be expected to vary with wrist posture, with the maximum shear predicted at 60 degrees of wrist flexion (Yoshii et al., 2008). High velocity tendon motion has been suggested to place the SSCT at a particularly high risk of shear injury (Yoshii et al., 2011). Hand and finger motions may also result in friction between the flexor digitorum muscles and the median nerve, also potentially leading to cumulative trauma development (Yoshii et al., 2008).
Noninflammatory tendon damage (tendinosis) has also been noted in CTS cases (Kerr et al., 1992). Tendinosis is characterized by microtears in the substance of the tendon and connective tissue, collagen degeneration, and fiber disorientation (Sharma & Maffulli, 2005). These characteristics are also observed during in vitro fatigue failure studies of tendons and studies of fatigue failure in animal studies (Barbe et al., 2013b; Schechtman & Bader, 1997; Shepherd & Screen, 2013; Sun et al., 2010). Patients with this syndrome also demonstrate decreased areal bone mineral density (BMD) in distal forearm bones (i.e., radius and ulna) and reduced bone in hand phalanges, as observed using quantitative ultrasound measurements (Erselcan, Topalkara, Nacitarhan, Akyuz, & Dogan, 2001; Kisala, Pluskiewicz,
