Fibromyalgia - Pathology

Nitric Oxide - updated: 04 May 2009

NO-mediated alterations in skeletal muscle nutritive blood flow and lactate metabolism in fibro

Pain. 2006 Jan;120(1-2):161-9. Epub 2005 Dec 22

McIver KL, Evans C, Kraus RM, Ispas L, Sciotti VM, Hickner RC. /p>

The purpose of these investigations was to determine if differences exist in skeletal muscle nutritive blood flow and lactate metabolism in women with fibromyalgia (FM) compared to healthy women (HC); furthermore, to determine if differences in nitric oxide-mediated systems account for any detected alterations in blood flow and lactate metabolism and contribute to exertional fatigue in FM. FM (n = 8) and HC (n = 8) underwent a cycle ergometry test of aerobic capacity, a muscle biopsy for determination of nitric oxide synthase (eNOS, nNOS, iNOS) content, and microdialysis for investigation of muscle nutritive blood flow and lactate metabolism. During prolonged (3h) resting conditions, the ethanol outflow/inflow ratio (inversely related to blood flow) increased in FM over time compared to HC (P < 0.05). FM also exhibited a reduced nutritive blood flow response to aerobic exercise (P < 0.05). There was an increase in dialysate lactate in response to acetylcholine in FM, and to sodium nitroprusside in both groups, with a greater rise in dialysate lactate in FM (P < 0.05). The iNOS protein content was higher in FM and was negatively correlated with total exercise time (r(2) = 0.462, P < 0.05). In conclusion: (1) There is reduced nutritive flow response to aerobic exercise and reduced maximal exercise time in FM that might relate to higher iNOS protein content and contribute to exertional fatigue in FM; (2) The increased dialysate lactate in FM in response to stimulation of NOS or a nitric oxide donor suggest that FM may be more sensitive than HC to the suppressive effect of nitric oxide on oxidative phosphorylation.

Publication Types:

• Study

Reduced tolerance of exercise in fibromyalgia may be a consequence of impaired microcirculation initiated by deficient action of nitric ox

Med Hypotheses. 2006;66(5):950-2

Kasikcioglu E, Dinler M, Berker E.

Although the underlying mechanism responsible for muscular fatigue and exercise intolerance remains to be elucidated, it is reported two major mechanisms, central and peripheral hypothesis. As a peripheral mechanism, there are few reports on abnormalities of the microcirculation in patients with fibromyalgia. The key point to note is that ischemia associated with a modest decline in tissue oxygen causes muscle fatigue. It has been shown that have been found low muscle levels of phosphates and abnormalities in microcirculation in fibromyalgia. Based on several novel data, production abnormalities of nitric oxide level might lead to symptoms of fatigue as a long term effect. There a vicious cycle concerning impairment of microcirculation in FM. The cycle is firstly initiated decrease of production of nitric oxide in the endothelial level by some trigger factors. Changed level of nitric oxide may cause microcirculation abnormalities in the tissue levels, muscular region. At the end of these phases, muscular fatigue and exercise intolerance may progressively develop in the FM. It is possible that this theory appears to provide a physiopathological explanation for decreased exercise capacity in patients with fibromyalgia. This paper describes a plausible mechanism for the development of exercise intolerance on microcirculation abnormalities

Publication Types:

• Medical Hypotheses

Current concepts in the pathophysiology of fibromyalgia: the potential role of oxidative stress and nitric oxide

Rheumatol Int. 2006 May;26(7):585-97

Ozgocmen S, Ozyurt H, Sogut S, Akyol O.

Fibromyalgia (FM) is a common chronic pain syndrome with an unknown etiology. Recent years added new information to our understanding of FM pathophysiology. Researches on genetics, biogenic amines, neurotransmitters, hypothalamic-pituitary-adrenal axis hormones, oxidative stress, and mechanisms of pain modulation, central sensitization, and autonomic functions in FM revealed various abnormalities indicating that multiple factors and mechanisms are involved in the pathogenesis of FM. Oxidative stress and nitric oxide may play an important role in FM pathophysiology, however it is still not clear whether oxidative stress abnormalities documented in FM are the cause or the effect. This should encourage further researches evaluating the potential role of oxidative stress and nitric oxide in the pathophysiology of FM and the efficacy of antioxidant treatments (omega-3 and -6 fatty acids, vitamins and others) in double blind and placebo controlled trials. These future researches will enhance our understanding of the complex pathophysiology of this disorder.

Publication Types:

• Review

Neurobiological basis of muscle pain

Schmerz. 1999 Feb 18;13(1):3-17

Mense S.

MECHANISMS IN THE LESIONED MUSCLE: The peripheral mechanism underlying the tenderness and pain during movement of a damaged muscle is the sensitization of muscle nociceptors. Ongoing activity of nociceptors causes spontaneous pain in addition to tenderness. Muscle pain (particularly that originating in myofascial trigger points) is often mislocalized because it is referred to other deep somatic tissues. The development of trigger points is a purely peripheral event, whereas the referral of muscle pain is based on central nervous mechanisms. MECHANISMS AT THE SPINAL LEVEL: The input from muscle nociceptors induces neuroplastic changes in the spinal cord and higher centres of the central nervous system. These changes are associated with an overexcitability of neurones (central sensitization) and contribute to hyperalgesia of patients. Resting activity of spinal neurones (and hence spontaneous pain) is strongly dependent on nitric oxide (NO). A muscle lesion is likely to lead to an inhibition of the homonymous muscle, it can, however, elicit spasm in another muscle. SUPRASPINAL MECHANISMS: Spinal neurones that mediate muscle pain are subjected to a strong descending inhibitory influence. The inhibitory tracts originate in the mesencephalon and medulla oblongata. A dysfunction of this inhibitory system might be involved in the pathogenesis of fibromyalgia

Publication Types:

• Study

Publication Types:

• Review