Acta Physiol 2016, 218, 3–4
ExActa
Fatigue
Fatigue and fatigue-related symptoms are a general
practitioner’s nightmare. Almost everybody knows
what is meant by the term. Everyone has experienced
it; yet no one is able to reliably quantify or document
fatigue or ‘feeling weaker than usual’ for a patient’s
record. A couple of years ago, a German company
came up with a clever service idea, mostly catering to
family physicians and first-line caregivers: Upon enter-
ing their office in the morning, they would find a fax
(yes, those were the times) on their desk, informing
them about the usually rare, exotic and dangerous dis-
eases which had been discussed in a popular health-
related TV show the night before, and whose main
symptoms would usually be unspecific, fatigue being
very high up on the list.
What defines fatigue? Is it, although intangible,
something real? Yes and no. Fatigue is subjective and
unspecific – that we guessed, and therefore, it must be
considered a symptom rather than a measurable sign
of disease. However, there seem to be three factors
that help us narrow it down a bit better: fatigue usu-
ally (i) begins gradually, (ii) differs from weakness as
fatigue can usually be alleviated by periods of rest
and, by CDC definition, and (iii) lasts longer than
6 months (Yancey & Thomas 2012). Moreover, it is
possible to discriminate physical from mental fatigue,
physical relating to muscle performance, mental fati-
gue relating to cognitive function, while weakness is
usually muscle weakness (Hawley & Reilly 1997).
Can physiological research help us understand fati-
gue better? Sleep research distinguishes fatigue from
somnolence, mainly through the duration of the symp-
tom and the fact that sleepiness is characterized by a
presumed impairment of the normal arousal mecha-
nism (Shen et al. 2006). Sleep disturbances, depression
and fatigue seem to be interrelated (Urrila et al.
2015), and novel insights into the homoeostatic regu-
lation of sleep may provide new clues to understand-
ing and fighting fatigue (McKinley et al. 2015,
Sundvik & Panula 2015).
In physiology, muscular fatigue does not always
denote the subjective symptom but rather a phe-
nomenon following exhaustive muscular exercise which
occurs during experimental setups that aim at better
understanding the electrophysiology of muscle contrac-
tion and relaxation (C
e et al. 2014, Hansen 2015).
Unaccustomed eccentric exercise not only leads to mus-
cle damage and soreness, but long-lasting effects on
muscle function (Semmler 2014). Chronic fatigue
© 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd, doi: 10.1111/apha.12756
syndrome predominantly affects women (Faro et al.
2016), yet women are less fatigable than men for simi-
lar intensity isometric fatiguing contractions (Hunter
2014).
Mental fatigue appears to be even harder to under-
stand than its physical counterpart, and both often
occur together. (Chronic) fatigue remains a clinical
diagnosis of unknown and possibly complex aetiology
that can be made only when other disease processes
are excluded. Potential contributing factors include a
spectrum of factors as diverse as vegetative and/or
immune dysfunction, central somatosensory control
mechanisms, genetic disposition and post-traumatic
disorders (Yancey & Thomas 2012, Alexandre et al.
2015, Al-Sajee et al. 2015).
Recently, animal models have been developed to
include both and which, as the authors hope, ‘could be
used to seek better preventive measures and to explore
the neural and molecular mechanisms involved in sev-
ere, long-lasting fatigue’ (Kanzaki et al. 2016).
Once underlying pathologies have been ruled out,
treatment options are limited to cognitive behaviour
therapy and graded exercise therapy – with moderate
effects at best. Interestingly, altitude adaptation seems
to affect supraspinal fatigue in human subjects (Good-
all et al. 2014). Fatigue is estimated to have a preva-
lence of up to 10% in the otherwise healthy general
population, no pharmacologic or alternative therapies
are effective (Yancey & Thomas 2012), patients suf-
fer, and the economic damage is considerable (Sabes-
Figuera et al. 2010). Let us get to work.
Conflict of interest
None.
P. B. Persson1 and A. Bondke Persson2
1
Institute of Vegetative Physiology, Charite-
Universitaetsmedizin Berlin,
Berlin, Germany
2
Charite-Universitaetsmedizin Berlin,
Berlin, Germany
E-mail: pontus.persson@charite.de
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3
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