In this issue of the Scandinavian Journal of Pain, two papers address pain in chronic fatigue syndrome (CFS): Andrea Polli and her co-workers report an association between exercise-induced changes in pressure pain thresholds and complement activity which was not present among healthy controls, suggesting a link between immune and pain modulation in CFS. Elin Bolle Strand and her co-workers found that pain is associated with anxiety and depression, and exerts a strong negative impact on CFS patients’ quality of life; these findings emphasize the importance of assessing and relieving pain in clinical care.
Pain is one of the most commonly reported bodily complaints among adult and adolescent CFS sufferers , , and is included in the most frequently used diagnostic criteria of CFS , . Still, a rather limited number of previous studies have specifically addressed pain in CFS. Thus, this symptom seems to be somewhat ignored by clinicians treating patients with CFS as well as researchers studying mechanisms and management of CFS .
1 Generalized increased central sensory sensitivity in CFS?
The underlying causes of increased pain experience in CFS remain to be properly understood, and a complex mixture of different mechanisms might be involved. Firstly, central sensitization has been advocated by some researchers . Evidence indeed suggests attenuated endogenous inhibitory control of pain  as well as overactive endogenous pain facilitation . Accordingly, CFS patients are shown to have abnormally low pressure pain thresholds indicating generalized hyperalgesia , . In addition, CFS patients report higher sensitivity towards other sensory stimuli as well, such as sounds and light , and maneuvers causing gentle strain on limb nerves and soft tissues induce pain more easily in CFS patients than in healthy controls . Thus, if there is central sensitization, then other kinds of sensory information may be affected as well . One might therefore speculate whether CFS patients possess a general trait of enhanced sensory-processing sensitivity .
2 Autonomic nervous system alterations and generalized low-grade inflammation in CFS
Secondly, peripheral phenomena might contribute importantly to pain experiences. CFS is characterized by decreased parasympathetic and increased sympathetic nervous activity , . Parasympathetic attenuation has been shown to be directly related to dysfunctional exercise-induced analgesia in CFS , whereas sympathetic enhancement is a well-known inducer of pain in many chronic pain conditions . Furthermore, several studies suggest a state of generalized low-grade inflammation in CFS , . Inflammation, in turn, might be a possible source of chronic pain , corroborating the findings of Polli and co-workers in the present issue. To complicate matter even further, perpetuating effects of vicious circles might be anticipated . For instance, increased sympathetic nervous activity might promote low-grade inflammation in CFS  which in turn might evoke a stronger noxious sensory experience due to central sensitization, resulting in a stress response characterized by increased sympathetic activity.
3 Emotional and cognitive alterations in CFS
Thirdly, emotional and cognitive processes are likely to be involved in CFS pain experiences. A strong bi-directional relationship between pain and anxiety has been documented in several previous studies , in line with the results reported by Strand and co-workers in the present issue. Accordingly, anxiety is common in CFS , and one CFS study demonstrated an association between pain severity and pain catastrophizing . Furthermore, expectancies are shown to exert a strong, modifying influence on pain experiences and might also have a “self-reinforcing” effect, thus contributing to chronicity . The possible role of expectancies has been only scarcely addressed in previous CFS research. However, one study reported an association between negative symptom expectancies and actual physical performance , whereas another study found that expectancies influence autonomic cardiovascular responses to gravity . Finally, a negative association between pain and cognitive performance in CFS was recently reported , and cognitive behavioral therapy, which is shown to improve fatigue in CFS , also effectively relieves pain , .
4 Pain and fatigue: expressions of similar alarm systems for disturbed homeostasis?
Summing up, further studies addressing the complex mechanisms underlying chronic pain in CFS are strongly needed. Not only may they contribute to better clinical care. They may also shed important light on the rather enigmatic entity of CFS. This assumption is grounded in some basic observation on the close similarities between pain and fatigue: Firstly, at a phenotypical level, there are several overlapping features between CFS and chronic pain states, in particular fibromyalgia , , and some researchers have suggested that these two conditions should actually be regarded as phenotypical variants of the same underlying pathophysiological process . Secondly, at the level of brain organization, a comparison of evidence from functional imaging studies suggests that the experience of fatigue is related to activity in neural networks that share some nodes with pain-associated networks , . Thirdly, from a functional point of view, both pain and fatigue might be considered evolutionary preserved “homeostatic alarms” that provide salient information to the individual of possible threats to body integrity , , : while pain signals possible or actual tissue damage, fatigue might be related to automatic and unconscious cost-benefit-calculations of energy consumption. In other words, the evolutionary “meaning” of fatigue might be to effectively prevent us from spoiling energy on a task with presumably low gain . Corroborating evidence has been provided from endurance sports research showing that the experience of fatigue is an important determinant of performance capacity independent on the energetic state of the working muscles . Of note, this functional conceptualization of pain and fatigue implies an unavoidable element of (unconscious) interpretation of the internal body state as well as the external world, which may or may not be correct; corollary, chronic pain and fatigue states might both be regarded as conditions of “misinterpretation”. It has been acknowledged for decades that pain might be experienced without stimulation of peripheral nociceptors . Likewise, it seems reasonable to assume that a sensation of fatigue might arise without any “external cause” immediately explaining it.
5 Implications for further CFS research
Given these basic similarities of pain and fatigue, CFS researchers might benefit strongly from a closer collaboration with pain researchers. On a practical level, this will imply access to a wide range of methodological tools, such as animal models and standardized experimental protocols, which are generally lacking in the field of CFS. On a conceptual level, the scientific tradition in pain research provides a much needed framework with its biopsychosocial perspective and simultaneous warning against body-mind-dichotomy and single-eyed reductionism . The studies by Elin Bolle Strand and her coworkers  as well as Andrea Polli and her coworkers  should be complemented for bringing pain into the CFS research field. Hopefully, future investigations of pain in CFS might re-vitalize a scientific field which appears to be somewhat paralyzed by controversies and blind alleys.
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About the article
Published Online: 2018-12-25
Published in Print: 2019-01-28
Conflict of interest: The author declares no conflict of interest.
Citation Information: Scandinavian Journal of Pain, Volume 19, Issue 1, Pages 5–8, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1515/sjpain-2018-2007.