Fibromyalgia Pathophysiology

Pathophysiology [0]

The pathophysiological factors of FM are not yet well known and continue to be the focus of much research. FM appears to be related to a pain-processing problem in the brain. In most cases, patients become hypersensitive to pain. The constant hypervigilance to pain can also be associated with psychological problems [1].

The main alterations observed in FM are dysfunctions in mono-aminergic neurotransmission, leading to elevated levels of excitatory neurotransmitters, such as glutamate and substance P, and decreased levels of serotonin and norepinephrine in the spinal cord at the level of descending anti-nociceptive pathways. Other anomalies observed are dopamine dysregulation and altered activity of endogenous cerebral opioids. Taken together, these phenomena seem to explain the central physiopathology of FM [2].

Over the years, peripheral pain generators have also been recognized as a possible cause of FM. In this case, patients manifest symptoms such as cognitive impairment, chronic fatigue, sleep disturbances, intestinal irritability, interstitial cystitis and mood disorders [3,4].

Peripheral abnormalities may contribute to increased nociceptive tonic supply in the spinal cord, which results in central sensitization. Other factors that appear to be involved in the pathophysiology of FM are neuroendocrine factors, genetic predisposition, oxidative stress and environmental and psychosocial changes [5,6].

FM appears to be more common in women than men for the following reasons: higher levels of anxiety and depression, altered behavior in response to pain, altered CNS input and hormonal effects related to the menstrual cycle [1].


0 Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update. Rosalba Siracusa, Rosanna Di Paola, […], and Daniela Impellizzeri.!po=46.2121

1 Bhargava J., Hurley J.A. StatPearls. StatPearls Publishing; Treasure Island, Fl, USA: 2021. Fibromyalgia.

2 Meyer H.P. Myofascial pain syndrome and its suggested role in the pathogenesis and treatment of fibromyalgia syndrome. Curr. Pain Headache Rep. 2002;6:274–283. doi: 10.1007/s11916-002-0048-z.

3 Clauw D.J. Fibromyalgia and related conditions. Mayo Clin. Proc. 2015;90:680–692. doi: 10.1016/j.mayocp.2015.03.014.

4 Malatji B.G., Mason S., Mienie L.J., Wevers R.A., Meyer H., van Reenen M., Reinecke C.J. The GC-MS metabolomics signature in patients with fibromyalgia syndrome directs to dysbiosis as an aspect contributing factor of FMS pathophysiology. Metabolomics. 2019;15:54. doi: 10.1007/s11306-019-1513-6.

5 Bradley L.A. Pathophysiology of fibromyalgia. Am. J. Med. 2009;122(Suppl. S12):S22–S30. doi: 10.1016/j.amjmed.2009.09.008.

6 Yunus M.B., Khan M.A., Rawlings K.K., Green J.R., Olson J.M., Shah S. Genetic linkage analysis of multicase families with fibromyalgia syndrome. J. Rheumatol. 1999;26:408–412.