Understanding Muscle Dysfunction in Chronic Fatigue Syndrome

Table 1

Summary of various proposed mechanisms underlying muscle dysfunction in CFS/ME.

Proposed mechanism underlying muscle dysfunction in CFS/ME	Study
Central sensitisation
Decreased pain threshold in patients.	Whiteside et al. (2004) [25], Meeus et al. (2010) [27]
Generalised hyperalgesia.	Nijs et al. (2012) [28], Vecchiet et al. (2003) [29]
Oxidative and nitrosative stress
Elevated TBARS prior to exercise in patients with history of severe infection.	Jammes et al. (2013) [22]
Elevated TBARS in patients with history of stress factors.	Jammes et al. (2012) [30]
Oxidative damage to endogenous epitopes, autoimmunity, and links with muscle fatigue.	Maes et al. (2006) [31]
Mitochondrial dysfunction
Mitochondrial function influenced by increased immune-inflammatory stress pathways in patients.	Broderick et al. (2010) [32]
Reduction in Th1 and Th17 function and movement toward Th2 dominant immunity.	Brenu et al. (2011) [33]
Reduction in mitochondrial enzyme level citrate synthase in patient muscle samples.	Skowera et al. (2004) [34]
Reduction in mitochondrial enzymes succinate reductase and cytochrome-C oxidase in skeletal muscle of patients.	McArdle et al. (1996) [35]
No difference in cytochrome-C oxidase levels in muscle biopsies.	Edwards et al. (1993) [36]
Patients reported to exhibit reduced levels of coenzyme Q10, with a significant inverse relationship between plasma coenzyme Q10 and fatigue severity measured via fibro fatigue scale.	Maes et al. (2009) [37]
Postexertional malaise (PEM) and immune function
Moderate intensity exercise and symptom flare (PEM) in patients, directly linked to IL-β, IL-12, IL-8, IL-10, and IL-13. Increased TNF-α postexercise in patient cohort postexercise.	White et al. (2004) [38]
Moderate intensity exercise also reported to induce a larger 48-hour postexercise area under the curve for IL-10 in patients.	Light et al. (2012) [39]
In comparison of 23 case control studies no evidence of a significant change in circulating pro/anti-inflammatory cytokines was reported. However, exaggerated complement system response, indicated by C4C split product level, enhanced oxidative stress and combined delayed and reduced antioxidant response.	Nijs et al. (2014) [40]
Muscle bioenergetic dysfunction
Evidence of significant () suppression in proton efflux immediately after exercise and significantly prolonged time to reach maximum proton efflux following low-level exercise (plantar flexion, 35% MVC).	Jones et al. (2010) [15]
Prolonged postexercise recovery from exercise in patients, indicated by marked increase in intramuscular acidosis compared to controls at a similar work rate. After each 3-minute bout of exercise (plantar flexion, 35% MVC), a 4-fold increase in the time taken to recover to baseline.	Jones et al. (2012) [2, 41]
No difference in intramuscular pH at rest, exhaustion, and early or late recovery following graded exercise to exhaustion. However, evidence of accelerated glycolysis at onset of exercise was illustrated by more rapid PCr depletion.	Wong et al. (1992) [42]
No consistent abnormalities in pH regulation following exercise when patient cohort is taken as a whole. However, 6 patients exhibited increased intramuscular acidification in relation to PCr depletion.	Barnes et al. (1993) [18]
In subanaerobic threshold exercise protocol only small subgroup of patients reported to have increased blood lactate responses to exercise.	Lane et al. (1998) [20, 43]
Abnormal AMPK activation and glucose uptake
No increase in AMPK phosphorylation or glucose uptake 16 hours following electrical pulse stimulation in CFS/ME patients. Compared to significant increases in both parameters in control participants.	Brown et al. (2015) [26]