http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2014; Early Online: 1–5 © 2014 Japan College of Rheumatology DOI: 10.3109/14397595.2014.886984
ORIGINAL ARTICLE
An evaluation of oxidative stress and antioxidant capacity in patients with myofascial pain syndrome İrfan Koca1, Ahmet Tutoglu2, Ahmet Boyacı2, Yavuz Pehlivan3, Hamit Yıldız4, Ibrahim Turkbeyler5, Edibe Sarıcicek6, Seyithan Taysi7, and Ahmet Mesut Onat3
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1Department of Physical Therapy and Rehabilitation, Gaziantep University, Faculty of Medicine, Gaziantep, Turkey, 2Department of Physical Therapy
and Rehabilitation, Faculty of Medicine, Harran University, Sanlıurfa, Turkey, 3Department of Rheumatology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey, 4Department of Internal Medicine, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey, 5Department of Internal Medicine, Faculty of Medicine, Adıyaman University, Adıyaman, Turkey, 6Department of Biochemistry, Ersin Aslan State Hospital, Gaziantep, Turkey, and 7Department of Biochemistry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey Abstract
Keywords
Objective. To evaluate total antioxidant capacity (TAC) and total oxidative stress (TOS) values in patients with myofascial pain syndrome (MPS). Method. The study comprised 38 patients diagnosed with MPS and 30 healthy volunteers. The age, body mass index (BMI) and pain scores (evaluation by visual analogue scales) of all the participants were recorded. The TAC, TOS and oxidative stress index (OSI) levels were compared between the MPS and control groups. Results. There was no significant difference between the MPS and control groups in respect of demographic characteristics. The TAC levels were determined to be significantly lower and TOS levels and OSI values, significantly higher in the MPS patients than in the control group. Conclusion. The results of this study determined that the oxidant/antioxidant balance was impaired in MPS patients and thus MPS can be considered to be related to an increase in oxidative stress.
Myofascial pain syndrome, Trigger point, Oxidant level, Antioxidant capacity
Introduction Myofascial pain syndrome (MPS) is a disease of the musculoskeletal system, characterised by hypersensitive points known as trigger points which are found in one or several muscles and/or connective tissue and in which symptoms or findings are seen such as pain, muscle spasm, sensitivity, limited movement, weakness and occasionally, autonomous dysfunction [1]. MPS is the most common cause of musculo-skeletal pain [2]. Although the etiology of MPS has not yet been fully clarified, a specific process of local ischaemia in the myofascial tissues is thought to lead to muscle spasms and the formation of trigger points [3]. It has been suggested that various factors such as poor posture, excessive use, chronic microtraumas, physical tiredness, inflammation, psychological stress, anxiety, depression and genetic causes are related to the occurrence of MPS [4,5]. Among the systemic factors held responsible for the etiology of MPS are vitamin deficiencies (B1, B6, B12, folic acid), mineral deficiencies such as potassium and calcium, iron deficiency anaemia, deficiencies of magnesium and lead which are necessary for normal muscle function, and metabolic or endocrine impairments (repeated hypoglycaemic episodes, hypothyroidism, oestrogen deficiency) [1]. It is also thought that there may be a predisposition to bacterial, viral and parasitic chronic infections. Transfer from hot to cold and damp air is also an aggravating factor [1,3]. Correspondence to: Dr. İrfan Koca, MD, Department of Physical Medicine and Rehabilitation, Gaziantep University School of Medicine, Gaziantep, Turkey. Tel: 90-342-3606060 (76280). E-mail: [email protected]
History Received 18 October 2013 Accepted 21 January 2014 Published online 26 March 2014
Several diseases such as rheumatoid arthritis, ankylosing spondylitis, osteoporosis, fibromyalgia and mechanical back pain have been determined to be related to oxidative stress [6–11]. However, to the best of our knowledge there are no studies which have evaluated oxidative stress or antioxidant capacity in MPS. This study aimed to contribute to literature on the point of clarification of MPS etiology by the evaluation of a comparison of total antioxidant capacity (TAC) and total oxidative stress (TOS) levels as indicators of oxidative-antioxidative balance in MPS patients and healthy controls.
Material and method Subjects The study comprised 38 patients diagnosed with MPS at Gaziantep University Medical Faculty Rheumatology Polyclinic between January 2013 and April 2013 and a control group of 30 healthy volunteers. Approval for the study was granted by the Local Ethics Committee and informed consent was obtained from all the participants. The anamnesis was taken from all the participants by the same physician and a detailed systemic examination was made. Age, body mass index (BMI) and pain scores were recorded for all participants. A full blood count, erythrocyte sedimentation rate, liver and kidney function tests, thyroid function tests and sex hormone profiles were evaluated for all participants. MPS diagnosis was made according to the criteria defined by Travell and Simons (and extended by Rosen) [1,2].
2 İ. Koca et al.
Mod Rheumatol, 2014; Early Online: 1–5
Table 1. Characteristic findings of the patient and control groups.
Study inclusion criteria 1. Aged 18–60 years and able to communicate 2. Patients with complaints of MPS-related neck and/or back pain and a band of tension which could be palpated over the trapezius muscle and active trigger points 3. Healthy volunteers with no complaints or disease
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Study exclusion criteria 1. Presence of cervical disc hernia, kyphosis, scoliosis or myelopathy 2. Previous neck or shoulder surgery 3. Stage 3–4 osteodegeneration 4. A diagnosis of fibromyalgia syndrome or inflammatory rheumatological disease 5. Pregnancy or in lactation 6. Presence of tumour, infection, psychiatric or systemic disease or haemorrhagic diastase 7. Hepatic, renal, endocrinal or cardiovascular disease 8. Tobacco or alcohol usage, vitamin supplements taken or medical treatment in the previous 4 weeks The pain intensity of all participants was evaluated subjectively with the visual analogue scale (VAS) [12]. Biochemical analyses Measurement of TAS-TOS level and calculation of OSI TAS and TOS levels were measured using a colorimetric method that was introduced by Erel [13,14]. The results were expressed as millimolar Trolox equivalent per liter (mmol Trolox equivalent/g protein) for TAS and micromolar hydrogen peroxide equivalent per liter (mmol H2O2 equivalent/g protein) for TOS. The ratio of TOS to TAS was accepted as the OSI. For the calculation, the resulting unit of TAS was converted to mmol/g protein, and the OSI value was calculated according to the following formula [15]: µmol H 2 O2 equivalent TOS g protein OSI (arbitrary unit) 100 m ol Trolox equivalent µ TAS g protein Statistical analysis Statistical analysis was made by SPSS 16.0 packet programme (SPSS for Windows 16.0, Chicago, IL). Parametric values are given as mean SD. Student’s t-test was used in the comparison of the data of the patient and control groups. Pearson correlation analysis
Age (years) Sex (female/male) BMI (kg/m2) Duration of disease (months) VAS
Patients (n 38) mean SD 31.4 3.2 29/11 25.3 3.4 24.7 5.2 6.7 2.1
Control (n 30) mean SD 32.8 3.4 22/8 26.2 4.1 1.8 3.4
Parameters
TAC (mmol Trolox equivalent/l) 0.93 0.11 TOS (mmol H2O2 equivalent/l) 22.15 4.5 OSI (Unit) 2.40 0.61 Correlation Correlation coefficient TAC and VAS r 0.292 TOS and VAS r 0.303 OSI and VAS r 0.336
0.05 0.05 0.05 0.001
MD, body mass index; VAS, visual analog scale. B p 0.05 accepted as significant. SD, standard deviation.
was used to define levels and relationships between variables. A value of p 0.05 was accepted as statistically significant.
Results When comparison was made in respect of the demographic characteristics of the MPS patients and healthy controls included in the study, no significant difference was seen between the groups regarding age, gender and body mass index (p 0.05) (Table 1). In the MPS patients and healthy controls a statistically significant correlation wasn’t determined between gender, age and BMI factors with TAC, TOS and OSI (p 0.05). When the MPS patients and healthy controls were compared in respect of oxidative and antioxidative parameters, the TAC levels of the MPS patients were seen to be statistically significantly lower (p 0.007). The TOS levels and OSI values of the MPS group were determined to be statistically significantly higher than those of the control group (respectively, p 0.045 and p 0.004). In the MPS patients a statistically significant positive correlation was determined between pain scores and TOS and OSI and a statistically significant negative correlation with TAC (respectively, r 0.303 and p 0.011, r 0.004 and p 0.004, r 0.292 and p 0.014). Gender, age and obesity factors adjusted odds ratios are given in Table 2 and Figures 1–3.
Discussion The results of the current study showed that the TAC levels of the MPS group were lower than those of the control group and the TOS levels were higher. These results lead us to consider that MPS may be related to impaired oxidative-antioxidative balance. In literature it has been reported that MPS is more often seen between the years of 30 and 49 and at twice the rate in males as females [16–18]. In the current study, the vast majority of the MPS patients were female (72.5%) and the mean age of the MPS patients was 31.4 years. In recent years there have been many studies which have evaluated the effect on an organism of stress and antioxidant
Table 2. Oxidative and antioxidative parameters of patients with myofascial pain syndrome and controls. Patients (n 38) mean SD
p value
Control (n 30) Odds ratio, mean SD Exp (B) 0.924 1.05 0.20 0.916 19.97 3.3 0.918 2.01 0.47
%95 Confidence interval Lower Upper 0.882 0.984 0.867 0.968 0.874 0.962
p value 0.007 0.045 0.004 0.014 0.011 0.004
TAC, total antioxidant capacity; TOS, total oxidant capacity; OSI, oxidative stress index. VAS, visual analog scale, r correlation coefficient, considered as statistically significant if p 0.05. Note: Gender, age and obesity factors adjusted odds ratios are given in table.
Oxidative status in myofascial pain syndrome 3
DOI 10.3109/14397595.2014.886984
10.00
10.00
8.00
VAS
VAS
8.00
6.00
6.00
4.00
4.00
1.50
2.00 0.60
0.70
0.80
0.90 TAC
1.00
1.10
1.20
Figure 1. In the MPS patients a statistically significant negative correlation was determined between pain scores (VAS) and TAC (mmol); (r 0.292, p 0.014). TAC, Total antioxidant capacity; VAS, Visual analog scale, r correlation coefficient, considered as statistically significant if p 0.05.
capacity. It has been reported that when reactive oxygen compounds produced physiologically in the body have not been removed to a sufficient level by antioxidant enzymes there may be a relationship with several complaints and diseases such as local tissue damage, organ dysfunction and rheumatoid arthritis, fibromyalgia, chronic back pain, osteoporosis, atherosclerosis, pancreas diseases, diabetes mellitus, peptic ulcer and carcinogenesis [8–11,16]. An increase in free oxygen radicals and a decrease in antioxidant capacity may be caused by ageing, stress, cigarette smoking, metabolic syndrome and hormone impairments [19]. In the current study, there was no difference between the mean ages and BMI of the MPS patients and the control group. In addition, in the MPS patients and healthy controls a statistically sig10.00
8.00
VAS
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2.00
6.00
4.00
2.00 15.00
20.00
25.00 30.00 TOS
35.00
40.00
Figure 2. In the MPS patients a statistically significant positive correlation was determined between pain scores (VAS) and TOS (mmol); (r 0.303, p 0.011). TOS, Total oxidant capacity; VAS, Visual analog scale, r correlation coefficient, considered as statistically significant if p 0.05.
2.00
2.50
3.00 OSI
3.50
4.00
4.50
Figure 3. In the MPS patients a statistically significant positive correlation was determined between pain scores (VAS) and OSI (arbitrary unit); (r 0.336, p 0.004). OSI, Oxidative Stress Index; VAS, Visual analog scale, r correlation coefficient, considered as statistically significant if p 0.05.
nificant correlation wasn’t determined between gender, age and BMI factors with TAC, TOS and OSI. Also, it was noticeable that while patients with no additional disease and non-smoking patients were included in the MPS group, the wide biochemical evaluation including the hormone panel was normal. In this respect, the oxidative-antioxidative imbalance of the MPS patients in this study is thought to be related to the process of the onset of the disease. MPS and fibromyalgia are two important sub-groups of non-articular rheumatic diseases. In literature, the role of oxidative stress in non-articular rheumatic diseases has only been researched in fibromyalgia. In a study by Eisinger et al. [20] in which the malondialdehyde levels, protein carbonyls and antioxidant status of 23 patients were evaluated, there was reported to be no significant difference determined between the patient and control groups. In another study by the same authors, the adenosine triphosphate and lactate dehydrogenase levels of fibromyalgia patients were reported to be at a lower level than those of the control group [21]. In the histological evaluation of the trapezium muscle of myalgia patients, ragged red fibrils and cytochrome-c-oxidase negative fibrils were widespread and the change in question was reported to result in damage to the oxidative metabolism [22]. In a study by Bagis et al. [23] of fibromyalgia patients, it was shown that serum malondialdehyde levels were higher, superoxide dismutase levels were lower and the oxidative-antioxidative balance was impaired. Several other studies have shown increased oxidative stress and decreased antioxidative capacity in fibromyalgia [9,24]. In the current study, which is the first to evaluate oxidant-antioxidant balance in MPS, the oxidative stress levels of the myofascial pain patients were found to be at a significantly higher level than those of the control group and the antioxidant capacity was lower, which shows similarities to the results of the studies on fibromyalgia. Travell and Simons [1] suggested that local ischaemia is created by vasoconstriction caused by increased calcium at the tissue level when a sarcoplasmic reticulum rupture occurs resulting from excessive loading on a muscle. Lund et al. [25] showed that there was low oxygen pressure in the muscles over trigger points. Fassbender and Wegner [18] reported that sensitive points in the muscles resulted
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4 İ. Koca et al. from local hypoxia in fibromyalgia. Impaired microcirculation of the sensitive points was defined by Jeschonneck et al. [26]. Bengtsson et al. [27] researched oxidative metabolism in fibromyalgia patients and determined that adenosine diphosphate and phosphoryl creatine levels had reduced and addenosine monophosphate and creatine levels had increased. When the results of these studies are taken into consideration, it is seen that local ischaemia plays a role in the physiopathology of both the trigger points of MPS and the sensitive points of fibromyalgia. Ischaemia is one of the factors which causes oxidative stress [7,19]. In this context, it can be considered that local ischaemia of the affected muscles played a role in the oxidative-antioxidative imbalance in the MPS patient of the current study. It has been reported that vasoconstriction on PG and LT caused by increased calcium levels within the cell of free oxygen radicals leads to endothelial damage and local ischaemia [7]. Therefore, there can be considered to be a vicious circle of ischaemia → oxidative stress → ischaemia, which may play a role in the physiopathology of MPS. Although it has been suggested that the excessive loading on the muscle results in a trigger point forming, plays a role in the physiopathology of trigger points in MPS, excessive loading does not result in trigger point forming in the muscles in every individual. Thus it can be considered that the forming of a trigger point by oxidative stress from idiopathic causes may be one of the facilitating factors in MPS. However, current knowledge of oxidative stress in MPS is insufficient to explain to what extent it is a cause and to what extent a result. Altindag and Celik [24] reported a significant negative correlation between pain scores and antioxidant capacity in fibromyalgia. In the current study, in the MPS patients, a negative correlation was determined between pain scores and antioxidant capacity and also between pain scores and oxidative stress. Thus, a relationship having been determined between oxidant and antioxidant capacity scores and clinical parameters in MPS, these parameters can be used to define the severity of the disease and to monitor treatment. Zaidi et al. [28] reported that vitamin E and vitamin C may be used as protection against the harmful effects of free oxygen radicals. Bramwell et al. [29] suggested that ascorbic acid may provide improvements in quality of life and clinical findings for fibromyalgia patients. Vitamin E was also shown to have a protective role in Hensen’s disease by Vijayaraghavan et al. [30]. In addition, it has also been reported that fruit and vegetables are rich in antioxidants and increase antioxidant capacity [31]. In recent years, with the widespread use of herbal remedies, Nigella sativa has been reported to have strong antioxidant potential as protection against free radicals [32]. As the current study is the first to evaluate oxidative stress and antioxidant capacity in MPS, it can be considered significant in respect of the findings of impaired oxidant-antioxidant balance correlated with pain scores in MPS. There are some limitations to the current study in that number of patients was limited in our study, it was a cross-sectional study and patients didn’t evaluate after MPS treatment.
Conclusion The results of this study show that MPS may be related to increased oxidative stress. It is thought that this relationship will be supported and fully clarified with future studies using vitamins C and E and other herbs with high antioxidant potential as supportive therapy in MPS.
Conflict of interest None.
Mod Rheumatol, 2014; Early Online: 1–5
References 1. Simons DG, Travell JG, Simons LS. Myofascial Pain and Dysfunction. The Trigger Point Manual. Upper Half of Body. 2nd ed. Baltimore: Lippincott, Williams and Wilkins; 1999. 2. Simons D. Review of enigmatic MTrPs as a common cause of enigmatic musculoskeletal pain and dysfunction. J Electromyogr Kinesiol. 2004;14(1):95–107. 3. Bron C, Dommerholt JD. Etiology of Myofascial Trigger Points. Curr Pain Headache Rep. 2012;16(5):439–44. doi:10.1007/s11916012-0289-4. 4. Kadi F, Waling K, Ahlgren C, Sundelin G, Holmner S, Butler-Browne GS, Thornel LE. Pathological mechanisms implicated in localized female trapezius myalgia. Pain. 1998;78(3):191–6. 5. Simons D. Clinical and etioloigical update of myofascial pain from trigger points. J Musculoskelet Pain. 1996;69:65. 6. Southorn PA, Powis G. Free radicals in medicine. II. Involvement in human disease. Mayo Clinic Proc. 1988;63(4):390–408. 7. Gower J, Healing G, Fuller B, Simpkin S, Green CJ. Protection aganist oxidative damage in cold-stored rabbit kidneys by deferrioamine and indomethacin. Crybiology. 1989;26(4):309–17. 8. Kaur H, Edmonds SE, Blake DR, Halliwell B. Hydroxyl radical generation by rheumatoid blood and knee joint synovial fluid. Ann Rheum Dis. 1996;55(12):915–20. 9. Ozgocmen S, Ozyurt H, Sogut S, Akyol O. Current concepts in the pathophysiology of fibromyalgia: the potential role of oxidative stres and nitric oxide. Rheumatol Int. 2006;26(7):585–97. 10. Brisby H, Ashley H, Diwan AD. In vivo measurement of facet joint nitric oxide in patients with chronic low back pain. Spine. 2007;32(14):1488–92. 11. Ozgocmen S, Kaya H, Fadillioglu E, Aydogan R, Yilmaz Z. Role of antioxidant systems, lipid peroxidation, and nitric oxide in postmenopausal osteoporosis. Mol Cell Biochem. 2007;295(1–2): 45–52. 12. Price DD, Bush FM, Long S, Harkins SW. A comparison of pain measurement characteristics of mechanical visual analogue and simple numerical rating scales. Pain 1994;56(2):217–26. 13. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. J Clin Biochem. 2004;37(2):112–9. 14. Erel O. A new automated colorimetric method for measuring total oxidant status. J Clin Biochem. 2005:38(12):1103–11. 15. Harma M, Harma M, Koçyigit A, Erel O. Increased DNA damage in patients with complete hydatidiform mole. Mutat Res. 2005;583(1): 49–54. 16. Ma TY, Hollander T, Freeman D. Oxygen free radical injury of IEC-18 small intestinal epithelial cell monolayers. Gastroenterology. 1991;100(6):1533–43. 17. Chandola HC, Chakraborty A. Fibromyalgia and myofascial pain syndrome-A dilemma. Indian J Anaesth. 2009;53(5):575–81. 18. Fassbender HG, Wegner K. Morphology and pathogenesis of softtissue rheumatism [abstract]. Z Rheumaforsch. 1973;32(9):355–74. 19. Augustin W, Wiswedel I, Noack H, Reinhenckel T, Reichelt O. Role of endogenous and exogenous antioxidants in the defense against functional damage and lipid peroxidation in rat liver mitochondria. Mol Cell Biochem. 1997;174(1–2):199–205. 20. Eisinger J, Zakarian H, Pouly E, Plantamura A, Ayavou T. Protein peroxidation, magnesium deficiency and fibromyalgia. Magnes Res. 1986;9(4):313–6. 21. Eisinger J, Plantamura A, Ayavou T. Glycolysis abnormalities in fibromyalgia. J Am Coll Nutr. 1994;13(2):144–8. 22. Larsson B, Björk J, Henriksson K, Gerdle B, Lindman R. The prevalences of cytochrome c oxidase negative and superpositive fibers and ragged-red fibers in the trapezius muscle of female cleaners with and without myalgia and of female healthy controls. Pain. 2000;84(2– 3):379–87. 23. Bagis S, Tamer L, Sahin G, Bilgin R, Guler H, Ercan B, Erdogan C. Free radicals and antioxidants in primary fibromyalgia: an oxidative stress disorder? Rheumatol Int. 2005;25(3):188–90. 24. Altindag O, Celik H. Total antioxidant capacity and the severity of the pain in patients with fibromyalgia. Redox Rep. 2006;11(3):131–5. 25. Lund N, Bengtsson A, Thorborg P. Muscle tissue oxygen pressure in primary fibromyalgia. Scand J Rheumatol. 1986;15(2):165–73. 26. Jeschonneck M, Grohmann G, Hein G, Sprott H. Abnormal microcirculation and temperature in skin above tender points in patients with fibromyalgia. Rheumatology. 2000;39(8):917–21.
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27. Bengtsson A, Henriksson KG, Larsson J. Reduced high-energy phosphate levels in the painful muscles of patients with primary fibromyalgia. Arthritis Rheum. 1986;29(7):817–21. 28. Zaidi SM, Al-Qirim TM, Banu N. Effects of antioxidant vitamins on glutathione depletion and lipid peroxidation induced by restraint stress in the rat liver. Drugs R D. 2005;6(3):157–65. 29. Bramwell B, Ferguson S, Scarlett N, Macintosh A. The use of ascorbigen in the treatment of fibromyalgia patients: a preliminary trial. Altern Med Rev 2000;5(5):455–62.
Oxidative status in myofascial pain syndrome 5 30. Vijayaraghavan R, Suribabu CS, Sekar B, Ommen PK, Kavithalakshmi SN, Madhusudhanan N, Panneerselvam C. Protective role of vitamin E on the oxidative stress in Hansen’s disease (Leprosy) patients. Eur J Clin Nutr. 2005;59(10):1121–8. 31. Cao G, Booth SL, Sadowski JA, Prior RL. Increases in human plasma antioxidant capacity after consumption of controlled diets high in fruit and vegetables. Am J Clin Nutr. 1998;68(5):1081–7. 32. Burits M, Bucar F. Antioxidant activity of Nigella sativa essential oil. Phytother Res. 2000;14(5):323–8.
ORIGINAL ARTICLE
An evaluation of oxidative stress and antioxidant capacity in patients with myofascial pain syndrome İrfan Koca1, Ahmet Tutoglu2, Ahmet Boyacı2, Yavuz Pehlivan3, Hamit Yıldız4, Ibrahim Turkbeyler5, Edibe Sarıcicek6, Seyithan Taysi7, and Ahmet Mesut Onat3
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1Department of Physical Therapy and Rehabilitation, Gaziantep University, Faculty of Medicine, Gaziantep, Turkey, 2Department of Physical Therapy
and Rehabilitation, Faculty of Medicine, Harran University, Sanlıurfa, Turkey, 3Department of Rheumatology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey, 4Department of Internal Medicine, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey, 5Department of Internal Medicine, Faculty of Medicine, Adıyaman University, Adıyaman, Turkey, 6Department of Biochemistry, Ersin Aslan State Hospital, Gaziantep, Turkey, and 7Department of Biochemistry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey Abstract
Keywords
Objective. To evaluate total antioxidant capacity (TAC) and total oxidative stress (TOS) values in patients with myofascial pain syndrome (MPS). Method. The study comprised 38 patients diagnosed with MPS and 30 healthy volunteers. The age, body mass index (BMI) and pain scores (evaluation by visual analogue scales) of all the participants were recorded. The TAC, TOS and oxidative stress index (OSI) levels were compared between the MPS and control groups. Results. There was no significant difference between the MPS and control groups in respect of demographic characteristics. The TAC levels were determined to be significantly lower and TOS levels and OSI values, significantly higher in the MPS patients than in the control group. Conclusion. The results of this study determined that the oxidant/antioxidant balance was impaired in MPS patients and thus MPS can be considered to be related to an increase in oxidative stress.
Myofascial pain syndrome, Trigger point, Oxidant level, Antioxidant capacity
Introduction Myofascial pain syndrome (MPS) is a disease of the musculoskeletal system, characterised by hypersensitive points known as trigger points which are found in one or several muscles and/or connective tissue and in which symptoms or findings are seen such as pain, muscle spasm, sensitivity, limited movement, weakness and occasionally, autonomous dysfunction [1]. MPS is the most common cause of musculo-skeletal pain [2]. Although the etiology of MPS has not yet been fully clarified, a specific process of local ischaemia in the myofascial tissues is thought to lead to muscle spasms and the formation of trigger points [3]. It has been suggested that various factors such as poor posture, excessive use, chronic microtraumas, physical tiredness, inflammation, psychological stress, anxiety, depression and genetic causes are related to the occurrence of MPS [4,5]. Among the systemic factors held responsible for the etiology of MPS are vitamin deficiencies (B1, B6, B12, folic acid), mineral deficiencies such as potassium and calcium, iron deficiency anaemia, deficiencies of magnesium and lead which are necessary for normal muscle function, and metabolic or endocrine impairments (repeated hypoglycaemic episodes, hypothyroidism, oestrogen deficiency) [1]. It is also thought that there may be a predisposition to bacterial, viral and parasitic chronic infections. Transfer from hot to cold and damp air is also an aggravating factor [1,3]. Correspondence to: Dr. İrfan Koca, MD, Department of Physical Medicine and Rehabilitation, Gaziantep University School of Medicine, Gaziantep, Turkey. Tel: 90-342-3606060 (76280). E-mail: [email protected]
History Received 18 October 2013 Accepted 21 January 2014 Published online 26 March 2014
Several diseases such as rheumatoid arthritis, ankylosing spondylitis, osteoporosis, fibromyalgia and mechanical back pain have been determined to be related to oxidative stress [6–11]. However, to the best of our knowledge there are no studies which have evaluated oxidative stress or antioxidant capacity in MPS. This study aimed to contribute to literature on the point of clarification of MPS etiology by the evaluation of a comparison of total antioxidant capacity (TAC) and total oxidative stress (TOS) levels as indicators of oxidative-antioxidative balance in MPS patients and healthy controls.
Material and method Subjects The study comprised 38 patients diagnosed with MPS at Gaziantep University Medical Faculty Rheumatology Polyclinic between January 2013 and April 2013 and a control group of 30 healthy volunteers. Approval for the study was granted by the Local Ethics Committee and informed consent was obtained from all the participants. The anamnesis was taken from all the participants by the same physician and a detailed systemic examination was made. Age, body mass index (BMI) and pain scores were recorded for all participants. A full blood count, erythrocyte sedimentation rate, liver and kidney function tests, thyroid function tests and sex hormone profiles were evaluated for all participants. MPS diagnosis was made according to the criteria defined by Travell and Simons (and extended by Rosen) [1,2].
2 İ. Koca et al.
Mod Rheumatol, 2014; Early Online: 1–5
Table 1. Characteristic findings of the patient and control groups.
Study inclusion criteria 1. Aged 18–60 years and able to communicate 2. Patients with complaints of MPS-related neck and/or back pain and a band of tension which could be palpated over the trapezius muscle and active trigger points 3. Healthy volunteers with no complaints or disease
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Study exclusion criteria 1. Presence of cervical disc hernia, kyphosis, scoliosis or myelopathy 2. Previous neck or shoulder surgery 3. Stage 3–4 osteodegeneration 4. A diagnosis of fibromyalgia syndrome or inflammatory rheumatological disease 5. Pregnancy or in lactation 6. Presence of tumour, infection, psychiatric or systemic disease or haemorrhagic diastase 7. Hepatic, renal, endocrinal or cardiovascular disease 8. Tobacco or alcohol usage, vitamin supplements taken or medical treatment in the previous 4 weeks The pain intensity of all participants was evaluated subjectively with the visual analogue scale (VAS) [12]. Biochemical analyses Measurement of TAS-TOS level and calculation of OSI TAS and TOS levels were measured using a colorimetric method that was introduced by Erel [13,14]. The results were expressed as millimolar Trolox equivalent per liter (mmol Trolox equivalent/g protein) for TAS and micromolar hydrogen peroxide equivalent per liter (mmol H2O2 equivalent/g protein) for TOS. The ratio of TOS to TAS was accepted as the OSI. For the calculation, the resulting unit of TAS was converted to mmol/g protein, and the OSI value was calculated according to the following formula [15]: µmol H 2 O2 equivalent TOS g protein OSI (arbitrary unit) 100 m ol Trolox equivalent µ TAS g protein Statistical analysis Statistical analysis was made by SPSS 16.0 packet programme (SPSS for Windows 16.0, Chicago, IL). Parametric values are given as mean SD. Student’s t-test was used in the comparison of the data of the patient and control groups. Pearson correlation analysis
Age (years) Sex (female/male) BMI (kg/m2) Duration of disease (months) VAS
Patients (n 38) mean SD 31.4 3.2 29/11 25.3 3.4 24.7 5.2 6.7 2.1
Control (n 30) mean SD 32.8 3.4 22/8 26.2 4.1 1.8 3.4
Parameters
TAC (mmol Trolox equivalent/l) 0.93 0.11 TOS (mmol H2O2 equivalent/l) 22.15 4.5 OSI (Unit) 2.40 0.61 Correlation Correlation coefficient TAC and VAS r 0.292 TOS and VAS r 0.303 OSI and VAS r 0.336
0.05 0.05 0.05 0.001
MD, body mass index; VAS, visual analog scale. B p 0.05 accepted as significant. SD, standard deviation.
was used to define levels and relationships between variables. A value of p 0.05 was accepted as statistically significant.
Results When comparison was made in respect of the demographic characteristics of the MPS patients and healthy controls included in the study, no significant difference was seen between the groups regarding age, gender and body mass index (p 0.05) (Table 1). In the MPS patients and healthy controls a statistically significant correlation wasn’t determined between gender, age and BMI factors with TAC, TOS and OSI (p 0.05). When the MPS patients and healthy controls were compared in respect of oxidative and antioxidative parameters, the TAC levels of the MPS patients were seen to be statistically significantly lower (p 0.007). The TOS levels and OSI values of the MPS group were determined to be statistically significantly higher than those of the control group (respectively, p 0.045 and p 0.004). In the MPS patients a statistically significant positive correlation was determined between pain scores and TOS and OSI and a statistically significant negative correlation with TAC (respectively, r 0.303 and p 0.011, r 0.004 and p 0.004, r 0.292 and p 0.014). Gender, age and obesity factors adjusted odds ratios are given in Table 2 and Figures 1–3.
Discussion The results of the current study showed that the TAC levels of the MPS group were lower than those of the control group and the TOS levels were higher. These results lead us to consider that MPS may be related to impaired oxidative-antioxidative balance. In literature it has been reported that MPS is more often seen between the years of 30 and 49 and at twice the rate in males as females [16–18]. In the current study, the vast majority of the MPS patients were female (72.5%) and the mean age of the MPS patients was 31.4 years. In recent years there have been many studies which have evaluated the effect on an organism of stress and antioxidant
Table 2. Oxidative and antioxidative parameters of patients with myofascial pain syndrome and controls. Patients (n 38) mean SD
p value
Control (n 30) Odds ratio, mean SD Exp (B) 0.924 1.05 0.20 0.916 19.97 3.3 0.918 2.01 0.47
%95 Confidence interval Lower Upper 0.882 0.984 0.867 0.968 0.874 0.962
p value 0.007 0.045 0.004 0.014 0.011 0.004
TAC, total antioxidant capacity; TOS, total oxidant capacity; OSI, oxidative stress index. VAS, visual analog scale, r correlation coefficient, considered as statistically significant if p 0.05. Note: Gender, age and obesity factors adjusted odds ratios are given in table.
Oxidative status in myofascial pain syndrome 3
DOI 10.3109/14397595.2014.886984
10.00
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6.00
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2.00 0.60
0.70
0.80
0.90 TAC
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1.20
Figure 1. In the MPS patients a statistically significant negative correlation was determined between pain scores (VAS) and TAC (mmol); (r 0.292, p 0.014). TAC, Total antioxidant capacity; VAS, Visual analog scale, r correlation coefficient, considered as statistically significant if p 0.05.
capacity. It has been reported that when reactive oxygen compounds produced physiologically in the body have not been removed to a sufficient level by antioxidant enzymes there may be a relationship with several complaints and diseases such as local tissue damage, organ dysfunction and rheumatoid arthritis, fibromyalgia, chronic back pain, osteoporosis, atherosclerosis, pancreas diseases, diabetes mellitus, peptic ulcer and carcinogenesis [8–11,16]. An increase in free oxygen radicals and a decrease in antioxidant capacity may be caused by ageing, stress, cigarette smoking, metabolic syndrome and hormone impairments [19]. In the current study, there was no difference between the mean ages and BMI of the MPS patients and the control group. In addition, in the MPS patients and healthy controls a statistically sig10.00
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2.00
6.00
4.00
2.00 15.00
20.00
25.00 30.00 TOS
35.00
40.00
Figure 2. In the MPS patients a statistically significant positive correlation was determined between pain scores (VAS) and TOS (mmol); (r 0.303, p 0.011). TOS, Total oxidant capacity; VAS, Visual analog scale, r correlation coefficient, considered as statistically significant if p 0.05.
2.00
2.50
3.00 OSI
3.50
4.00
4.50
Figure 3. In the MPS patients a statistically significant positive correlation was determined between pain scores (VAS) and OSI (arbitrary unit); (r 0.336, p 0.004). OSI, Oxidative Stress Index; VAS, Visual analog scale, r correlation coefficient, considered as statistically significant if p 0.05.
nificant correlation wasn’t determined between gender, age and BMI factors with TAC, TOS and OSI. Also, it was noticeable that while patients with no additional disease and non-smoking patients were included in the MPS group, the wide biochemical evaluation including the hormone panel was normal. In this respect, the oxidative-antioxidative imbalance of the MPS patients in this study is thought to be related to the process of the onset of the disease. MPS and fibromyalgia are two important sub-groups of non-articular rheumatic diseases. In literature, the role of oxidative stress in non-articular rheumatic diseases has only been researched in fibromyalgia. In a study by Eisinger et al. [20] in which the malondialdehyde levels, protein carbonyls and antioxidant status of 23 patients were evaluated, there was reported to be no significant difference determined between the patient and control groups. In another study by the same authors, the adenosine triphosphate and lactate dehydrogenase levels of fibromyalgia patients were reported to be at a lower level than those of the control group [21]. In the histological evaluation of the trapezium muscle of myalgia patients, ragged red fibrils and cytochrome-c-oxidase negative fibrils were widespread and the change in question was reported to result in damage to the oxidative metabolism [22]. In a study by Bagis et al. [23] of fibromyalgia patients, it was shown that serum malondialdehyde levels were higher, superoxide dismutase levels were lower and the oxidative-antioxidative balance was impaired. Several other studies have shown increased oxidative stress and decreased antioxidative capacity in fibromyalgia [9,24]. In the current study, which is the first to evaluate oxidant-antioxidant balance in MPS, the oxidative stress levels of the myofascial pain patients were found to be at a significantly higher level than those of the control group and the antioxidant capacity was lower, which shows similarities to the results of the studies on fibromyalgia. Travell and Simons [1] suggested that local ischaemia is created by vasoconstriction caused by increased calcium at the tissue level when a sarcoplasmic reticulum rupture occurs resulting from excessive loading on a muscle. Lund et al. [25] showed that there was low oxygen pressure in the muscles over trigger points. Fassbender and Wegner [18] reported that sensitive points in the muscles resulted
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4 İ. Koca et al. from local hypoxia in fibromyalgia. Impaired microcirculation of the sensitive points was defined by Jeschonneck et al. [26]. Bengtsson et al. [27] researched oxidative metabolism in fibromyalgia patients and determined that adenosine diphosphate and phosphoryl creatine levels had reduced and addenosine monophosphate and creatine levels had increased. When the results of these studies are taken into consideration, it is seen that local ischaemia plays a role in the physiopathology of both the trigger points of MPS and the sensitive points of fibromyalgia. Ischaemia is one of the factors which causes oxidative stress [7,19]. In this context, it can be considered that local ischaemia of the affected muscles played a role in the oxidative-antioxidative imbalance in the MPS patient of the current study. It has been reported that vasoconstriction on PG and LT caused by increased calcium levels within the cell of free oxygen radicals leads to endothelial damage and local ischaemia [7]. Therefore, there can be considered to be a vicious circle of ischaemia → oxidative stress → ischaemia, which may play a role in the physiopathology of MPS. Although it has been suggested that the excessive loading on the muscle results in a trigger point forming, plays a role in the physiopathology of trigger points in MPS, excessive loading does not result in trigger point forming in the muscles in every individual. Thus it can be considered that the forming of a trigger point by oxidative stress from idiopathic causes may be one of the facilitating factors in MPS. However, current knowledge of oxidative stress in MPS is insufficient to explain to what extent it is a cause and to what extent a result. Altindag and Celik [24] reported a significant negative correlation between pain scores and antioxidant capacity in fibromyalgia. In the current study, in the MPS patients, a negative correlation was determined between pain scores and antioxidant capacity and also between pain scores and oxidative stress. Thus, a relationship having been determined between oxidant and antioxidant capacity scores and clinical parameters in MPS, these parameters can be used to define the severity of the disease and to monitor treatment. Zaidi et al. [28] reported that vitamin E and vitamin C may be used as protection against the harmful effects of free oxygen radicals. Bramwell et al. [29] suggested that ascorbic acid may provide improvements in quality of life and clinical findings for fibromyalgia patients. Vitamin E was also shown to have a protective role in Hensen’s disease by Vijayaraghavan et al. [30]. In addition, it has also been reported that fruit and vegetables are rich in antioxidants and increase antioxidant capacity [31]. In recent years, with the widespread use of herbal remedies, Nigella sativa has been reported to have strong antioxidant potential as protection against free radicals [32]. As the current study is the first to evaluate oxidative stress and antioxidant capacity in MPS, it can be considered significant in respect of the findings of impaired oxidant-antioxidant balance correlated with pain scores in MPS. There are some limitations to the current study in that number of patients was limited in our study, it was a cross-sectional study and patients didn’t evaluate after MPS treatment.
Conclusion The results of this study show that MPS may be related to increased oxidative stress. It is thought that this relationship will be supported and fully clarified with future studies using vitamins C and E and other herbs with high antioxidant potential as supportive therapy in MPS.
Conflict of interest None.
Mod Rheumatol, 2014; Early Online: 1–5
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