Hadrevi, J., Barbe, M. F., Ortenblad, N., Frandsen, U., Boyle, E., Lazar, S., … Sogaard, K. (2019). Calcium fluxes in work‐related muscle disorder: Implications from a rat model. BioMed Research International, 2019, 5040818. doi:10.1155/2019/5040818 / Hindawi / CC BY‐4.0.
Muscle myalgia (i.e., muscle pain) is associated with muscle stiffness, weakness, and increased tension (Ohlsson, Attewell, Johnsson, Ahlm, & Skerfving, 1994). Like muscle fatigue, dysfunctional Ca2+ homeostasis has been implicated in skeletal muscles of patients suffering from chronic neck and shoulder pain (Hadrevi, Ghafouri, Larsson, Gerdle, & Hellström, 2013). A study of biopsied myalgic muscle from human subjects showed a decreased abundance of calcequestrin (Casq1) together with an increased abundance of sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA1) (Hadrevi et al., 2016). This may indicate an increased uptake of Ca2+ into the sarcoplasmic reticulum, although with a reduced buffering capacity in that structure. Additionally, increased interstitial concentrations of inflammatory mediators, such as bradykinins, kallidin, lactate, pyruvate, and K+, have been found in patients with chronic severe trapezius myalgia (Gerdle et al., 2008; Gerdle et al., 2014). Injections of pro‐inflammatory cytokines such as tumor necrosis factor alpha have also been shown to increase muscle pain/myalgia by activating the firing of pain‐related nerve fibers (i.e., nociceptors) (Kehl, Trempe, & Hargreaves, 2000; Schafers, Sorkin, & Sommer, 2003).
Muscle fibrosis is also hypothesized to be a key factor in motor dysfunction, increased discomfort, and pain observed in patients with MSDs (Backman, Andersson, Wennstig, Forsgren, & Danielson, 2011; Barbe, Gallagher, & Popoff, 2013a; Barbe et al., 2013b; Stauber, 2004). Tissue fibrosis is thought to distort dynamic properties of tissue and contribute to functional declines perhaps due to adherence of adjacent structures or encapsulation of nerve related pain fibers (Driscoll & Blyum, 2011; Fisher et al., 2015; Pavan et al., 2014; Zugel et al., 2018). Fibrotic muscle changes may occur at any point in the musculotendinous unit including within the muscle fibers and at the musculotendinous junction (Abdelmagid et al., 2012; Fedorczyk et al., 2010; Fisher et al., 2015; Hilliard, Amin, Popoff, & Barbe, 2020). There are several possibilities for the continued increase in fibrogenic proteins (which include collagen, transforming growth factor beta 1 (TGF‐β1), and connective tissue growth factor/cell communication network factor 2 (CTGF/CCN2) and in the assembly and remodeling of the extracellular matrix with chronic overload or repeated injury, including (a) dysregulation of negative feedback loops and therefore continued 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