Circadian Rhythms and Fibromyalgia
Many of the symptoms of this syndrome, including difficulty sleeping, fatigue, malaise, myalgias, gastrointestinal complaints, and decreased cognitive function, are similar to those observed in individuals whose circadian pacemaker is abnormally aligned with their sleep-wake schedule or with local environmental time. Abnormalities in melatonin and cortisol, two hormones whose secretion is strongly influenced by the circadian pacemaker, have been reported in women with fibromyalgia. [1]
Fibromyalgia and sleep problems are all characterized by circadian rhythm imbalance. Circadian rhythm [2] underlies the endogenous, 24-hour cycle of human function. The central nervous system regulates adrenal function via the hypothalamic-pituitary-adrenal axis, and stress disrupts the balance. Circadian rhythm is present each step of the way in this process. Circadian rhythm and the resulting secretion of endocrine hormones and neurotransmitters depend upon the transmission of light through the eyes.
The pineal responds to the pacemaker [3] functioning in the suprachiasmatic nuclei (SCN) in the hypothalamus by secreting melatonin. When light is received through the retina of the eyes, it travels via the retino-hypothalamic tract to the SCN and a signal is sent to the pineal gland (Strassman, 1991). Ablation or scarring of the SCN eliminates circadian rhythm. Trauma causes a disruption in the function of the hypothalamus (Rossi, 1986) and attachment traumas of early life result in low levels of melatonin (Reiter & Robinson, 1995; Shafii & Shafii, 1990).
Disturbances of body circadian rhythm can contribute to poor sleep, fatigue and exacerbations of other symptoms of FM [1]. In humans circadian rhytmicity is originated by hypothalamus and FM patients have a disturbed hypothalamic cortical adrenal axis [4,5].
Many studies show that FM patients have decreased levels of growth hormone (GH) [6,7] and its metabolites, particularly during the night [8].
Moutz et al. [9] used neuro-imaging of FM patients to examine regional cerebral blood flow (rCBF) to specific brain structures and showed that rCBF to the thalamus and caudate nucleus was decreased in FM patients.
Moreover, the loss GH secretion during slow wave sleep may be linked to lesions in dorsal medial nucleus of the thalamus [10] suggesting that rCBF may be involved in the GH secretion abnormalities observed in FM patients.
Frequent alpha wave intrusion during delta wave sleep has been associated with the reduced production of GH and insuline-like growth factor 1 (IGF1) [11,12]. Moreover, GH and IGF1 are involved in the repair of muscle micro traumas. Sleep disturbances may affect physiological healing mechanisms after muscle-tissue damage. This may alter the transmission of sensory stimuli from damaged muscle tissue to nervous system and enhance the perception of muscle pain [13]. About
90% of FM patients had inadequate GH response to exercise [7] and one-third significantly low circulating IGF-1 levels [13]. GH replacement therapy significantly improved symptoms and reduced the number of tender points in FM patients [14].
Elevated cerebral spinal fluid levels of substance P were also found in patients with FM [15]. Substance P, a neuractive peptide, is widely distributed throughout the nervous system and may contribute to arousal [16]. Experimental studies showed that substance P influences nociception and sleep via a neurokinin pathway [17].
These findings seem to support the hypothesis that a decrease in substance P levels may reduce the arousing effects of substance P on the sleep/waking brain function in FM patients.
1 Circadian Rhythms of Women with Fibromyalgia. Elizabeth B. Klerman, Don L. Goldenberg, Emery N. Brown, Anne M. Maliszewski, And Gail K. Adler. The Journal of Clinical Endocrinology & Metabolism https://academic.oup.com/jcem/article/86/3/1034/2847502?login=false
2 Circadian Rhythm: What it is, what shapes it, and why it’s fundamental to getting quality sleep. April 8, 2022. Eric Suni, Alex Dimitriu https://www.sleepfoundation.org/circadian-rhythm
3 A Web of Circadian Pacemakers. Ueli Schibler, Paolo Sassone-Corsi. https://www.cell.com/action/showPdf?pii=S0092-8674%2802%2901225-4
4 Adler GK, Kinsley BT, Hurwitz S, Mossey CJ, Goldemberg DL (1999) Reduced hypothalamic-pituitary and syumpathoadrenal responses to hypoglicemia in women with fibromyalgia in women with fibromyalgia syndrome. Am J Med 840: 684-697.
5 Demitrack MA, Crofford LJ (2002) Evidence for and pathophysiologic implications of hypothalamic-pituitary-adreanl axis dysregulation in fibromyalgia and chronic fatigue syndrome. Current Rheumattol. Reports 4: 306-312.
6 Bennett RM (2002) Adult growth hormone deficiency in patients with fibromyalgia. Curr Rheumatol Rep 4: 306-312.
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8 Leal-Cerro A, Povedano J, Astorga R, Gonzalez M, Silva H, et al. (1999) The growth hormone (GH)-releasing hormone-GH-insulin-like growth factor-1 axis in patients with fibromyalgia syndrome. J Clin Endocrinol Metab 84: 3378-3381.
9 Moutz JM, Bradley LA, Modell JG, Alexander RW, Alexander M, et al. (1995) Fibromyalgia in women: abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Artritis Rheum 38: 926-938.
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12 Prinz PN, Moe KE, Dulberg EM, Larsen LH, Vitiello MV, et al. (1995) Higher plasma IGF-1 levels are associated with increased delta sleep in healthy older men. Journal of Gerontology Series A Biological Sciences and medical Sciences 50: 222-226.
13 Bennett RM, Clark SR, Campbell SM, Burckhardt CS (1992) Low levels of somatomedin C in patients with the fibromyalgia syndrome. A possible link between sleep and muscle pain. Arthritis Rheum 35: 1113-1116.
14 Bennett RM, Clark SC, Walczyk J (1998) A randomized, double-blind, placebo controlled study of growth hormone in the treatment of fibromyalgia. Am J Med 104: 227-231.
15 Vaerøy H, Helle R, Førre O, Kåss E, Terenius L (1988) Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis. Pain 32: 21-26.
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17 Andersen ML, Nascimento DC, Machado RB, Roizenblatt S, Moldofsky H, et al. (2006) Sleep disturbance induced by substance P in mice. Behav Brain Res 167: 212-218.