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8 Articles in this Series
Bench to Bedside: Clinical Tips From APS Poster Presentations
New Pain Research Underscores the Importance of Sufficient Rest
The Benefits of Exercise for Pain Management
Exercise as Postoperative Analgesic?
How Race Affects Pain
Increased Centralized Pain in African American Patients
Managing Post-Tonsillectomy Pain in Obese Children
Research Offers Insight Into Fibromyalgia and Pain

Research Offers Insight Into Fibromyalgia and Pain

Fibromyalgia syndrome (FMS) is a chronic disorder that is known to cause muscle pain, fatigue, sleeping issues, and tender points on the body—all of which can have detrimental effects on a patient’s quality of life (QOL). Self-report and performance measures have indicated that the allodynia and hyperalgesia caused by FMS can be attributed to impairments in cognition and focus, sometimes referred to as “fibro fog.”

What causes some patients to experience fibro fog isn’t well understood. One possible explanation is that the frequent pain FMS patients experience triggers an overuse of attentional resources, possibly leading to feelings of fatigue. However, fatigue may indicate more than a connection to chronic pain. Fatigue may serve as a marker for depleted cognitive resources in patients suffering from FMS.

The causes of fibrofog aren't well understood but new research is shedding light on the role of fatigue as a marker for depleted cognitive resources in patients with fibromyalgia. In a new study presented at this year’s annual meeting of the American Pain Society (APS), researchers sought to better understand the pain and fatigue seemingly related to fibro fog. The study recruited 96 FMS patients (all female, mean age = 42.59, SD = 10.67), measuring their pain and fatigue levels using a visual analog scale and the Profile of Mood States, respectively.1

To measure the patient’s fibro fog levels, patients were assessed with the Mental Clutter Scale, a reliable and valid tool for assessing FMS patients’ mental fogginess.2 The researchers then tested the mediating effects of fatigue and produced bias-corrected confidence intervals.

The researchers found pain intensity significantly associated with fibro fog (b = 0.35, SE = 0.10, 95% BC = .18 to .53) and fatigue (b = 1.23, SE = .22, 95% BC CI = 0.79 to 1.67). “However, when fibro fog was regressed on both pain intensity and fatigue, only fatigue remained significant (b = 0.16, SE = .04 95% BC CI = .08 to .23),” the authors reported.

Further bootstrap analysis also revealed that fatigue significantly mediated pain intensity’s effect on fibro fog (b = .19, SEboot = .06, 95% BC CI = .10 to .32), suggesting that measuring fatigue could provide a useful marker for gauging a patient’s depleted cognitive resources, the authors noted.

Researchers are learning more about the relationship between sleep and fatigue problems associated with FMS. FMS, a symptom-based illness, is commonly associated with chronic fatigue syndrome (CFS), a disorder that is also difficult to diagnose and causes extreme fatigue.  

Because FMS and CFS often exist in the same patient group and share the same core symptoms (pain, extreme fatigue, sleeping problems, and cognitive difficulties), some practitioners have suggested the conditions could be considered interchangeable.3 Indeed, some past studies have not even differentiated between FMS and CFS.4

However, insomnia appears to be a more prevalent issue with FMS patients, compared to the sleep-disordered breathing (SDB) that is more commonly seen in CFS patients.5 Keep in mind, FMS patients can also experience a range of sleep disturbances6 but until recently, it has been difficult for doctors to understand how FMS sleeping patterns relate to their other symptoms. Now, new research has started to crack open what lack of sleep does to FMS patients, and how compromised sleeping patterns can turn symptoms from bad to worse.

FMS and The Significant Effects of Delayed Circadian Phase

Depression is another typical symptom of FMS, and it is particularly relevant for FMS patients who have a delayed circadian phase, which is a tendency to fall asleep later at night and wake up later in the day. However, few studies have explored the topic of circadian activity rhythms (CAR) in FMS patients and the role CAR can play in how FMS patients experience other related symptoms, especially pain and depression.

According to the findings of a second study presented at the APS meeting, CAR could play a far more influential role in FMS symptomology than previously assumed. The study examined 274 women (mean age = 45.1 years, SD = 11.0, range = 21 – 54 years), assessing their activity levels through a 7-day actigraphy and measuring their depression and pain levels using the Center for Epidemiological Studies Depression Scale (CESD) and tender point (TP) pain severity.7

In order to measure the patients’ CAR levels, researchers referred to the actigraphy data and used a cosine model designed for each individual patient to find the acrophase, which is the time of the day when the actigraphy hits the peak of the activity curve. The researchers found a “weak, yet significant” linear relationship did exist between acrophase and CESD scores (r = 0.17, p = 0.005) and between acrophase and TP pain severity (r = 0.20, p = 0.002). To further explore this, the researchers split the patients into 3 groups based on their acrophase levels:

  •  Advanced acrophase group (<25th percentile: acrophase earlier than 2:38 PM)
  •  Average acrophase group (25th to 75th percentile: acrophase between 2:38 PM and 4:39 PM)
  •  Delayed acrophase group (>75th percentile: acrophase after 4:39 PM)

The more delayed a patient’s acrophase was, the worse her symptoms appeared to be.

According to the authors, this preliminary evidence provides insight into how delayed acrophase can influence pain and mood symptoms in FMS patients, something that merits further investigation given that past research has posited that abnormalities in circadian rhythmicity were not a primary cause of FMS or its related symptoms.8

With new emerging data suggesting worsening CARs indeed may correlate to worsening symptoms, taking consideration of how late at night a patient falls asleep and wakes up in the day may offer useful insights into a patient’s QOL, informing better treatment decisions. There are other ailments commonly associated with FMS, as well, like irritable bowel syndrome (IBS).9 How co-occurring problems like delayed CAR and co-occurring IBS relate to one another in an FMS patient is an expanding area of inquiry, one that may offer further practical insights in the near future.



  1. Bell T, Shelley-Tremblay J. Fatigue mediates the relationship between pain and cognitive dysfunction in fibromyalgia. Poster presented at: Annual Meeting of the American Pain Society; May 11-14, 2016; Austin, TX. Poster #222.
  2. Leavitt F, Katz RS. Development of the Mental Clutter Scale. Psychol Rep. 2011;109(2):445-452.
  3. Wessely S, Nimnuan C, Sharpe M. Functional somatic syndromes: One or many? Lancet. 1999;354:936-939.
  4. Abbi B, Natelson BH. Is chronic fatigue syndrome the same illness as fibromyalgia: Evaluating the ‘single syndrome’ hypothesis. Q J Med. 2013;106:3-9.
  5. Pejovic S, Natelson BH, Basta M, et al. Chronic fatigue syndrome and fibromyalgia in diagnosed sleep disorders: A further test of the ‘unitary’ hypothesis. BMC Neurol. 2015;15:53.
  6. Diaz-Piedra C, Di Stasi LL, Baldwin CM, et al. Sleep disturbances of adult women suffering from fibromyalgia: A systematic review of observational studies. Sleep Med Rev. 2015;21:86-99.
  7. Neikrug A, Iacob E, Okifuji A, et al. Circadian activity rhythms in women with fibromyalgia. Poster presented at: Annual Meeting of the American Pain Society; May 11-14, 2016; Austin, TX. Poster #223.
  8. Klerman EB, Goldenberg DL, Brown EN, et al. Circadian rhythms of women with fibromyalgia. J Clin Endocrinol Metab. 2001;86(3):1034-1039.
  9. Lange G, Natelson BH. Chronic Fatigue Syndrome. In: Mayer EA, Bushnell MC, editors. Functional Pain Syndromes: Presentation and Pathophysiology. Seattle: IASP; 2009:245-264.



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