FMS is a distinct rheumatic syndrome characterized by a specific list of diagnostic criteria identified in 1990 by the American College of Rheumatology.(1) The symptoms include widespread diffuse pain in a specific distribution and at specific trigger points, fatigue and morning stiffness, and muscle pain after activity.(2,3) FMS is the third most common rheumatic disorder seen in rheumatology practice, after osteoarthritis and rheumatoid arthritis. It is estimated that 3-6 million people in the United States are affected by FMS, with most cases being women of ages 25-45 years.(4) FMS is generally treated with analgesic and antidepressant medications, as well as modified exercise programs.
The muscular aches and tenderness of FMS are associated with changed perception of pain, abnormal sleep patterns and reduced brain serotonin, and reductions of high-energy phosphate levels in muscle.(5,6) The subsequent reduced high-energy metabolism has been associated with increased pyruvicemia and decreased LDH muscular isoenzyme LDH4, whereas lactate production in forearm ischemic exercise test (FIET) is normal or decreased.(7,8) Other controversial phosphate abnormalities, such as low phosphocreatinine/inorganic phosphate (PCr/Pi), have also been noted in people with FMS, similar to those observed in hypothyroidism or McArdle's syndrome.(9) To further explore these findings, a study was recently done in France by Eisinger et al.(10) to investigate whether FMS is related to an impairment of carbohydrate metabolism.
Eighty-six subjects were divided into four groups. Group 1 (n = 35) comprised 22 female and 14 male healthy controls ages 22-96 years. Group 2 (n = 25) included 23 females and 2 males ages 30-87 years, all diagnosed with FMS. They exhibited generalized pain, sleep disorders, and anxiety in the absence of any secondary physical causes. Group 3 (n = 10) included 9 females and 1 male ages 37-89 years with untreated HO, as assessed by measurement of thyroid-stimulating hormone. Group 4 (n = 15) included 11 females and 4 males with OACP ages 37-82 years. Chronicity of pain was defined as pain present related to osteoporosis or osteoarthritis for more than 6 weeks, with less than 4 tender points, and associated with decreased physical activity.
Excluded from the study were people with a diagnosis of other severe disease, atypical nutrition habits, chronic alcoholism, obesity, or treatment with adrenoceptor blocking or stimulating agents, fluoride, or B vitamins. Approximately one-third of groups 1 and 2 and two-thirds of groups 3 and 4 had a controlled dietary intake of 1800-2000 kcal/day. Red blood cells were assessed for levels of pyruvate kinase (PK), glyceraldehyde phosphate dehydrogenase (GAPDH), 2,3-diphosphoglycerate (DPG), and ATP. Whole blood was assessed for pyruvicemia. Plasma lactic acid (LA) was measured before and 2, 4, 6, and 8 minutes after FIET to generate the defined lactate maximal increase (DL), and serum was tested for LDH muscular isoenzymes. Serum phosphate (P) and growth hormone (GH) were measured in groups 1-4, and serum thiamin pyrophosphate (TPP) and erythrocyte and leukocyte blood cell magnesium (MgE and MgL) were measured in groups 1-3.
The results obtained related to measured parameters of glycolysis as shown in Table 1.(Table 1 omitted) Significant differences between the study groups were found for GAPDH, LDH-4, ATP, DL, and pyruvate. Compared to healthy controls, people with FMS had significantly decreased LDH-4 (23%), GAPDH (18%), ATP (5%), and DL (64%). Pyruvate levels were increased by 83%.
The results obtained related to measured parameters of glycolysis regulation are shown in Table 2.(Table 2 omitted) Significant differences between the study groups were noted for MgE, MgL, and GH, with FMS differences specifically observed for MgL and GH. Compared to healthy controls, people in the FMS group had significantly increased levels of MgL (50%) and decreased levels of GH (36%).
Microscopic and physical findings associated with FMS include glycogen accumulation and decreased type II fibers on muscle biopsy,(11) muscle pain and stiffness with abnormal relaxation,(12) abnormal sympathetic activity, and energy crisis in muscle.(3) Glycolysis abnormalities such as those noted in HO(13,14) were demonstrated in the subjects with FMS. The findings of Eisinger et al. showed a pattern of reduced DL associated with a marked rise in pyruvate, a decrease in ATP, and an increase in the pyruvate/L ratio. Their observations perhaps explain some of the physical findings characteristic of FMS.
Eisinger et al. noted that the increased pyruvate/L ratio seen in FMS has also been reported in thiamin deficiency. They also cite the fact that abnormalities in muscular LDH isoenzymes have also been described in muscular dystropy(15) and hereditary LDH muscular subunit deficit,(16) and might therefore explain the reduced DL associated with a marked rise in pyruvate. Several prior studies,(17,18) however, have not implicated mitochondrial oxidative enzyme defects as a cause of FMS. Abnormalities of GH secretion could also partially explain the carbohydrate impairment.
Eisinger et al. speculate that the energy crisis that causes the FMS symptoms might evolve as a result of glycolysis impairment, which induces failure of thiamin activation and results in serotonin depletion. When these actors are associated with decreased GH production, carbohydrate metabolism and subsequent energy production could become impaired. Thus, the authors urge that people with FMS be treated with metabolic therapy rather than analgesics. Although future studies may indicate that metabolic-oriented therapy is important and appropriate, at present analgesia still remains an important component of treatment for people with FMS.(19,20)
Further studies to supplement these very interesting observations are needed. Given the prevailing age group (25-45) and female population of people with FMS, more research about a possible hormonal interaction within the glycolysis cycle might also produce valuable information about this perplexing ailment.
1. Wolfe F, Smythe H, Yunus M, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Arthritis Rheum 1990;33: 160-72
2. Bennett R. The fibromyalgia syndrome: myofascial pain and the chronic fatigue syndrome. In: Kelly W, ed. Textbook of rheumatology. Philadelphia: W. B. Saunders, 1993:471-83
3. Bennett R, Smythe H, Wolfe, F. Recognizing fibromyalgia. Patient Care 1992;March 15:211-28
4. Boulware D, Schmid L, Baron M. The fibromyalgia syndrome: could you recognize it? Postgrad Med 1990;82:211-4
5. Yunus MB, Nasi A, Calabro J. Primary fibromyalgia (fibrositis); clinical study of 50 patients with matched normal controls. Semin Arthritis Rheum 1981;11:151-70
6. Henriksson KG, Bengtsson A. Muscular change in fibromyalgia and their significance in diagnosis. In Fricton JR, Awad A, eds. Advances in pain research and therapy. New York: Raven Press, 1990:259-67
7. Eisinger J, Mechtouf K, Plantamura A, et al. Anomalies biologiques au cours des fibromyalgies: I. Lactacidemie et pyruvicemie. Lyon Mediterranee Med 1992;28:851-4
8. Valen PA, Flory W, Pauwel M, et al. Forearm ischemic testing and plasma ATP degradation products in primary fibromyalgia. Arthritis Rheum 1988;31:115
9. Mathur AK, Gatter RA, Bank WJ, et al. Anormal P NMR spectroscopy of painful muscles of patients with fibromyalgia. Arthritis Rheum 1988;31:523
10. Eisinger J, Plantamura A, Ayavou T. Glycolysis abnormalities in fibromyalgia. J Am Coll Nutr 1994;13: 144-8
11. Kalyan-Raman UP, Kalyan-Raman K, Yunus MB. Muscle pathology in primary fibromyalgic syndrome: a light microscopic histochemical and ultra structural study. J Rheum 1984;11:808-13
12. Smythe HA. Fibrositis as a disorder of pain modulation. Chin Rheum Dis 1975;5:823-3211.
13. Kaminsky P, Robin-Lherbier B, Brunotte F, et al. Energetic metabolism in hypothyroidism skeletal muscle, as studied by phosphorus magnetic resonance spectroscopy. J Clin Endocrinol Metab 1992;74: 124-9
14. Schwark WS, Singhal RL, Ling GH. Glyceraldehyde phosphate dehydrogenase activity in developing brain during experimental cretinism. Biochim Biophys Acta 1972;273:308-17
15. Ibrahim GH, Essam AA, Kottke FJ. Interstitial myofibrositis: serum and muscle enzymes and lactate deshydrogenase isoenzymes. Arch Phys Med Rehabil 1974;55:23-8
16. Kanno T, Sudo K, Takeuchi I, et al. Hereditary deficiency of lactate deshydrogenase M subunit. Clin Chim Acta 1980;108:267-76
17. Bennett RM. Muscle physiology and cold reactivity in fibromyalgia syndrome. Rheum Dis Clin North Am 1989;1 5:135-47
18. Soderlund K, Hultman E, Bengtsson A. Is a reduced energy store of energy production rate a cause for fibromyalgia? Scand J Rheum 1992;21(suppl 94):66
19. Goldenberg D. Treatment of fibromyalgia syndrome. Rheum Dis Clin North Am 1989;15:61-71
20. Bennett R. Beyond fibromyalgia: ideas on etiology and treatment. J Rheum 1989;19(suppl):185-91
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