S¸ YILDIZ1, MZ KIRALP1, A AKIN1, I KESKIN1, H AY1, H DURSUN1 AND M CIMSIT2
1GATA Haydarpas¸a Military Hospital, Istanbul, Turkey;
2Istanbul University Medical Faculty, Istanbul, Turkey
Fibromyalgia syndrome (FMS) is characterized by longstanding multifocal pain with generalized allodynia/hyperalgesia.
There are several treatment methods but none has been specifically approved for this application. We conducted a randomized controlled study to evaluate the effect of hyperbaric oxygen (HBO) therapy in FMS (HBO group: n = 26; control group: n = 24). Tender points and pain threshold were assessed before, and after the first and fifteenth sessions of therapy. Pain was also scored on a visual analogue scale (VAS). There was a significant reduction in tender points and VAS scores and a significant increase in pain threshold of the HBO group after the first and fifteenth therapy sessions.
There was also a significant difference between the HBO and control groups for all parameters except the VAS scores after the first session. We conclude that HBO therapy has an important role in managing FMS.
KEY WORDS: ALGOMETER; HYPERBARIC OXYGEN THERAPY; FIBROMYALGIA; PAIN THRESHOLD;
VISUAL ANALOGUE SCALE Introduction
Fibromyalgia syndrome (FMS) is a chronic musculoskeletal disorder. It is characterized by widespread pain, tenderness at specific anatomical sites (i.e. tender points) and clinical manifestations such as fatigue, sleep disturbance and irritable bowel syndrome.1,2
Its prevalence is 1 – 3% and it occurs predominantly in females, commonly between the ages of 40 and 50 years.3
The most frequently reported musculoskeletal or fibrous connective tissue symptoms are aches and pains, stiffness, swelling in soft tissues, tender points and muscle spasms or nodules.2 There is a global decrease in pressure pain threshold rather than specific changes limited to the tender points.4 The aetiopathology of FMS is still not known although it is thought that the disease is caused by several interacting factors such as muscle overload, poor spinal posture, disturbed sleep, psychogenic factors, local hypoxia5,6 and reduced concentrations of high-energy phosphate. Fassbender and Wegner have hypothesized that local hypoxia causes degenerative changes in the muscles in FMS.5
There is no proven effective long-term management program for FMS.2 Hyperbaric oxygen (HBO) therapy has been used worldwide for the past 30 years to treat many diseases, including conditions caused by local hypoxia or ischemia such as diabetic wounds, chronic non-healing wounds, compromised skin grafts and flaps, and cerebral ischaemia.7 HBO therapy involves breathing 100% oxygen via an endotracheal tube, mask or hood in a pressure chamber at pressures higher than 1 atmosphere absolute (ATA). During HBO therapy, the increased concentration and the partial pressure of oxygen provide increased oxygenation to the whole body. Oxygen tension is raised to 10 – 13 times above its normal level when a patient breathes 100% oxygen at 2.8 ATA.
When the circulation is compromised, there sultant ischemia lowers the concentration of adenosine triphosphate (ATP) and increases the concentration of lactic acid. Increased oxygen delivery to the tissue with HBO may prevent tissue damage in ischemic tissues by decreasing the tissue lactic acid concentration and helping maintain the ATP level.
The aim of HBO therapy in patients with FMS is to reduce muscle hypoxia and increase levels of high-energy phosphate.
Patients and methods
We carried out a randomized, double blind controlled study of HBO therapy in patients with FMS.
Patients with FMS (meeting the American College of Rheumatology diagnostic criteria8) who had persistent symptoms in spite of medical and physical therapy were included in the study. Patients were randomized (alternately) to receive HBO therapy (HBO group) or normal air (control group). After randomization, patients were evaluated for their suitability to receive HBO therapy. Patients with contraindications were excluded from the study by the evaluating physician. The evaluating physician did not know which therapy the patient was to have received. The physician administering therapy was the only one to know which therapy the patients received. This disclosure was necessary for evacuation purposes in the event of an emergency during a therapy session.
The HBO group underwent 15 90-min sessions of HBO therapy at 2.4 ATA. There was one session per day for 5 days of the week. The control group breathed air at 1 ATA for 90 min following the same schedule as the HBO group. During the study period, no other therapeutic modalities were used. All patients gave informed consent and the GATA Military Medical Faculty Ethical Committee approved the study.
The patients were examined just before and after the first and fifteenth therapy sessions. At each examination, the number of tender points was determined by palpation and the number of tender points was noted. The pain threshold was measured with an algometer and pain evaluated using a visual analogue scale (VAS).
To measure the pressure pain threshold the top of the algometer was placed on the tender point and the pressure was increased until the patient confirmed that they felt pain.9 The contact area was 1 cm2 and covered with 2-mm thick rubber to minimize irritation of the skin. The compression pressure was increased gradually by approximately 1 kg/s. The patient was asked to say ‘yes’ when he or she began to feel pain or any discomfort. A needle on the manometer scale recorded the pressure pain threshold in kilograms. 264 S¸ Yildiz, MZ Kiralp, A Akin et al. Hyperbaric oxygen therapy in Fibromyalgia syndrome
Numerical variables are presented as mean ± SD. The Wilcoxon test and Student’s t-test were used for within group (HBO group only) and between group comparisons.
A P-value of < 0.05 was accepted as statistically significant. SPSS version 11.0 software (SPSS Inc., Chicago, IL, USA) was used for all statistical calculations.
There were 26 patients (17 female, nine male; mean age 40.46 ± 4.79 years) in the HBO group and 24 (18 female, six male; mean age 39.88 ± 4.71 years) in the control group. The symptoms of FMS had been present for an average of 4 ± 1.1 years (range 1 – 30). The number of tender points, pain threshold (as measured by the algometer) and the VAS pain scores for both groups before and after treatment are given in.
Mean ± SD of the number of tender points, pain threshold and visual analogue Scale (VAS) pain scores of
patients with fibromyalgia syndrome in the group receiving hyperbaric oxygen (HBO group) and control group
Before treatment After first session After 15 sessions
HBO Control HBO Control HBO Control
(n = 26) (n = 24) (n = 26) (n = 24) (n = 26) (n = 24)
No. of tender points 14.96 ± 1.50 15.25 ± 1.18 12.46 ± 1.10a,b 13.75 ± 1.07b 6.04 ± 1.18a 12.54 ± 1.10
Pain threshold 0.71 ± 0.09 0.75 ± 0.13 0.93 ± 0.09a,b 0.81 ± 0.12b 1.33 ± 0.12a 0.84 ± 0.12
VAS score 64.62 ± 10.28 68.33 ± 10.28 59.23 ± 8.44a 60.42 ± 8.58 31.54 ± 8.34a 55.42 ± 6.58
A Statistically significant difference between first and fifteenth sessions of HBO therapy (P < 0.001). b
Statistically significant difference between study and control group (P < 0.001).
1 Bennett RM: The fibromyalgia syndrome. In: Textbook of Rheumatology, 5th edn (Kelley WN, Harris ED, Ruddy S, Sledge
CB eds). Philadelphia: WB Saunders Company, 1997; pp511 – 519.
2 Krsnich-Shriwise S: Fibromyalgia syndrome: an overview. Phys Ther 1997; 77: 68 – 75.
3 Yunus MB, Holt GS, Masi AT, Aldag JC: Fibromyalgia syndrome among the elderly. Comparison with younger patients. J Am Geriatr Soc 1988; 36: 987- 995.
4 Tunks E, McCain GA, Hart LE, Teasell RW, Goldsmith CH, Rollman GB, et al: The reliability of examination for tenderness in patients with myofascial pain, chronic fibromyalgia and controls. J Rheumatol 1995; 22: 944 – 952.
5 Fassbender HG, Wegner K: Morphologie und Pathogenese des Weichteilrheumatismus. [Morphology and pathogenesis of soft-tissue rheumatism]. Z Rheumaforsch 1973; 32: 355 – 374. 6 Lund N, Bengtsson A, Thorborg P: Muscle tissue oxygen pressure in primary fibromyalgia. Scand J Rheumatol 1986; 15: 165 – 173. 7 Jain KK: Physical, physiological, and biochemical aspects of hyperbaric oxygenation. In: Textbook of Hyperbaric Medicine, 2nd ed Received for publication 26 November 2003. Accepted subject revision 13 December 2003. Revised accepted 21 January 2004
6 S¸ Yildiz, MZ Kiralp, A Akin et al.
Hyperbaric oxygen therapy in fibromyalgia syndrome that any condition, such as establishment of abnormal
motor patterns, that could lead to constant muscle hypoxia might be a possible cause of fibromyalgic pain.
Another study concluded that in patients with primary FMS, the muscle oxygenation is abnormal or low, at least in the trigger point area of the muscle as shown by an oxygen multipoint electrode on the muscle surface.6
Patients with FMS have been found to have a lower density of capillaries in muscles,13 thicker capillary endothelium, derangement of muscle capillaries after tourniquet-induced ischaemia and more frequent endothelial changes,14 and lower values of muscle blood flow.10 These changes are either caused by localized hypoxia or cause the hypoxia.15
A study of pain in patients with FMS produced data consistent with the hypothesis that the intensity of pain experienced in patients with FMS is associated with increased synthesis of nitric oxide (NO).16
Another study, based on the recent evidence that NO is involved in hyperoxic vasoconstriction, tested the hypothesis that decreased NO availability to brain tissue during hyperbaric oxygen exposure contributes to decreases in regional cerebral blood flow. We think that HBO therapy may be effective for treating patients with FMS because of the decreasing NO effect.17
In clinical experience, HBO therapy often stimulates production of red granulation tissue consisting mainly of new blood vessels and the supporting collagenous matrix. The vascular endothelial growth factor (VEGF) concentration significantly increases with HBO. If VEGF concentration directly responds to hyperoxia, it may be possible for VEGF to stimulate angiogenesis.18 This is another reason why HBO therapy may be effective in FMS and may play an important role in its management.
There is no information about HBO therapy for managing FMS in the current literature. The proposed role of hypoxia in FMS, however, prompted us to evaluate the effectiveness of hyperoxia provided by HBO therapy. In our study, we think that HBO therapy was successful in breaking the pain-hypoxia vicious cycle since it decreased the number of tender points and VAS pain scores by increasing the pain threshold. HBO may be an effective and relatively cheap (US$15/h) alternative treatment modality for patients with FMS, especially for those with chronic pain.
7 S¸ Yildiz, MZ Kiralp, A Akin et al. Hyperbaric oxygen therapy in fibromyalgia syndrome (Jain KK, Neubauer R, Correa JG, Camporesi EM, eds). Seattle-Toronto-Bern-Göttingen: Hogrefe & Huber Publishers, 1996; pp11 – 26.
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9 Lautenschläger J: Die Erfassung der Druckpunkte bei generalisierter Tendomyopathie-GTM. (Evaluation of tender points in fibromyalgia) (in German). In: Generalisierte Tendomyopathie (Fibromyalgie) (Müller W, ed). Darmstadt: Steinkopff, 1991; pp95 – 104.
10 Bennett RM, Clark SR, Goldberg L, Nelson D, Bonafede RP, Porter J, et al: Aerobic fitness in patients with fibrositis. A controlled study of respiratory gas exchange and 133xenon clearance from exercising muscle. Arthritis Rheum 1989; 32: 454 – 460.
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12 Bengtsson A, Henriksson KG: The muscle in fibromyalgia – a review of Swedish studies. J Rheumatol 1989; 19 (Suppl): 144 – 149.
13 Lindh M, Johansson G, Hedberg M, Henning GB, Grimby G: Muscle fiber characteristics, capillaries and enzymes in patients with fibromyalgia and controls. Scand J Rheumatol 1995; 24: 34 – 37.
14 Gidlöf A, Lewis DH, Hammarsen F: The effect of prolonged ischemia of human skeletal muscle. A morphometric analysis. Int J Microcirc Clin Exp 1987; 7: 67 – 86.
15 Lindman R, Hagberg M, Bengtsson A, Henriksson KG, Thornell L-E: Capillary structure and mitochondrial volume density in the trapezius muscle of chronic trapezius myalgia, fibromyalgia and healthy subjects. J Musculoskelatal Pain 1995; 3: 5 – 22.
16 Larson AA, Giovengo SL, Russell IJ, Michalek JE: Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways. Pain 2000; 87: 201 – 211.
17 Demchenko IT, Boso AE, Bennett PB, Whorton AR, Piantadosi CA: Hyperbaric oxygen reduces cerebral blood flow by inactivating nitric oxide. Nitric Oxide 2000; 4: 597 – 608.
18 Sheik AY, Gibson JJ, Rollins MD, Hoph HW, Hussain Z, Hunt TK: Effect of hyperoxia on vascular endothelial growth factor levels in a wound model. Arch Surg 2000; 135: 1293 – 1297.