EFFECT OF LOW-LEVEL LASER THERAPY ON PAIN , QUALITY OF LIFE AND SLEEP IN PATIENTS WITH FIBROMYALGIA : DOUBLE-BLINDED RANDOMIZED CONTROLLED TRIAL ( STUDY PROTOCOL )

Background: Low-level laser therapy (LLLT) has been widely used as a strategy for the adjuvant treatment of musculoskeletal disorders. The light-tissue interaction (photobiostimulation) promotes analgesic and anti-inflammatory effects and tissue healing, which could justify the recommendation of this therapy for patients with fibromyalgia, leading to an improvement in pain and possible minimization of the social impact of this disease. The present study is proposing to evaluate the effect of LLLT on tender points in patients with fibromyalgia, correlating the results with quality of life and sleep. Methods/Design: Sixty patients with fibromyalgia will be treated at the Integrated Health Center and the Sleep Laboratory of the Postgraduate Program in Rehabilitation Sciences of the Nove de Julho University located in the city of Sao Paulo, Brazil. After fulfilling the eligibility criteria, a clinical evaluation and assessments of pain and sleep quality will be carried out and self-administered quality of life questionnaires will be applied. The 120 volunteers will be randomly allocated to an intervention group (LLLT; n =60 ) or control group (CLLLT; n = 60). Both groups will receive applications three times a week for four weeks, totalizing 12 sessions. However, only the LLLT group will receive an energy dose of 6 J. All applications will be performed on previously identified tender points. A standardized 50-minute exercise program will be performed after the laser application. The patients will be evaluated with regard to the primary outcome (pain) using the following instruments: a visual analogue scale, the McGill Pain Questionnaire and pressure algometry. The secondary outcome (quality of life and sleep) will be assessed with the following instruments: Medical Outcomes Study 36-item Short-Form Health Survey, the Fibromyalgia Impact Questionnaire, Berlin Questionnaire, Epworth Sleepiness Scale and polysomnography. The statistical analysis will involve intra-group comparisons using the one-tailed, paired Student’s t-test. Inter-group comparisons will involve a homogeneity test based on Pearson’s chi-square statistic with Yates’ correction, when necessary. The level of significance for the statistical analysis will be set at 5% (p < 0.05). Trial Registration: The protocol for this study is registered with the Brazilian Registry of Clinical Trials – ReBEC(RBR-42gkzt) Background: Fibromyalgia is a chronic musculoskeletal condition characterized by generalized pain of an etiology that has not yet been fully clarified. It is defined by the American College of Rheumatology (ACR) as generalized pain for at least three months in combination with sensitivity in 11 or more of the 18 points sensitive to palpation in different parts of the body, known as tender points [1]. Although this pain syndrome is frequent and was first described more than 150 years ago, the study of fibromyalgia was hindered by confusion regarding its terminology and overlap with other pain syndromes. The current definition is based on the classification criteria developed by the ACR in 1990 [2]. According to Weidebach (2002) [3], fibromyalgia, which was previously denominated fibrositis, was not a clinically well-defined condition before the 1970s, when the first findings were published that led the way to more in-depth studies. Unlike what was thought in the past, fibromyalgia is not an inflammatory condition and does not lead to joint impairment or deformities. However, the chronic nature of this condition has a negative impact on quality of life. The most widely accepted theory is that fibromyalgia is caused by an abnormality in pain modulation mechanisms – a central nervous system disorder in regulating sensitivity to pain. Thus, an individual may exhibit a reduction in serotonin (neurotransmitter of the inhibitory descending system) and in increase substance P (neuroexcitatory substance involved in the conduction of pain) in the central nervous system [4]. Fibromyalgia is often associated with other syndromes, such as fatigue, sleep disorders, morning stiffness and psychological disorders, such as anxiety and depression. Sleep disorders are closely linked to somatic symptoms in patients with fibromyalgia and not to their personality. The most common complaints are difficulty falling asleep, frequent awakening during the night, difficulty getting back to sleep, restless superficial sleep and early rising, the consequences of which are non-restorative sleep and a sensation of weariness, which contribute toward a poor quality of life. Thus, non-restorative sleep is an important aspect among the manifestations of fibromyalgia, which makes the investigation into primary sleep disorders essential to the assessment of affected individuals [5, 6]. The complexity of the factors involved regarding both diagnosis and adequate treatment underscores the need for further studies aimed at broadening knowledge on the effects of this condition on patients. There are several treatment options for fibromyalgia, such as drugs [7,8], psychotherapy [9], hydrotherapy [10], electrotherapy [11], exercise[12] and laser therapy[13,14]. However, there is no consensus or defined protocol regarding the use of these treatment options. Low-level laser therapy (LLLT) is one of the more recent pain treatment modalities in the field of physical therapy. According to Laakso et al. [15], the analgesic effect of phototherapy may be mediated by hormonal/opioid mechanisms, the responses of which depend directly on the dose and wavelength used to irradiate the tissue. Thus, the parameters directly affect the results. LLLT is also reported to act on peripheral neural stimulation and the regulation of microcirculation, interrupting pain mechanisms and promoting analgesia [16]. The normalization of microcirculation and the capacity of neural transmission obtained through laser therapy have been described as responsible for the interruption of the vicious circle that gives rises to and perpetuates pain [13]. In last ten years, important advances have occurred in the therapeutic use of photobiostimulation with low-level lasers. Such advances have occurred due to a greater understanding of the mechanisms of action involved as well as technological developments and the publication of relevant studies and research related to the advantages obtained with the use photobiostimulation in clinical practice. However, the lack of consensus regarding therapeutic protocols hinders multi-center comparisons of the many clinical trials published. Thus, a number of scientific papers have been drafted to establish a therapeutic protocol for the use of photbiostimulation with regard to exposure time, intensity, energy density, application mode and application site. A considerable number of studies have demonstrated the remission of pain in patients with fibromyalgia through the use of LLLT. However, this is not yet a well-established therapy and comparisons of controlled clinical trials are rare; moreover, there are problems regarding the standardization of treatment [13, 14,17,18]. In the investigation of complex phenomena such as fibromyalgia, the application of multiple methodological techniques enables a better assessment and understanding of such phenomena [19]. The aim of the proposed study is to assess the analgesic effect of LLLT on tender points in patients with fibromyalgia and establish correlations with quality of life and sleep. Methods and design Characterization of proposed study The proposed study will be carried out with 120 patients with fibromyalgia. A double-blind randomized controlled trial will be carried out at the Sleep Study Laboratory of the Postgraduate Program in Rehabilitation Sciences of the Nove de Julho University (UNINOVE) and the UNINOVE Integrated Health Center, located in the city of Sao Paulo, Brazil. (Figure 1) Characterization of subjects The sample will be comprised of 120 patients with fibromyalgia with a clinical diagnosis based on the ACR criteria. The subjects will be screened at the UNINOVE Rheumatology Clinic, located at Rua Claudio Batista, S/N – Postal code: 49060-100 – São Paulo, SP. Telephone: + 55 11 3218-1744. Composition of sample The required sample size was determined for the primary outcome variable, i.e. overall score of Fibromyalgia Impact Questionnaire (FIQ). According to Bennett et al. [20], a clinically relevant change is a 15-20% reduction in the total FIQ score (which equals to a ~10-15 points reduction). Assuming an unilateral alternative (i.e. the intervention reduces impact of fibromyalgia), we can detect differences of at least 15% with a power of 95% and α of 0.05 with two groups (intervention and usual control group) of 45 participants, with a mean in the FIQ of ~70 and a standard deviation of ~20 points. Assuming a maximum lost of follow-up of 30%, we will recruit a total of 60 women with fibromyalgia for each group. We will recruit a total of 120 women with fibromyalgia (i.e., one LLLT intervention groups and control group of 60 persons each). Inclusion criteria The following criteria will be adopted as requirements for inclusion in the study: • A clinical diagnosis of fibromyalgia based on ACR criteria; • Cognitive level sufficient for understanding the procedures and following the instructions; • Agreement to participate in the study and the signing of a statement of informed consent after receiving clarifications regarding the objectives of the study. Exclusion criteria Patients with the following will be excluded from the study: • Psychiatric disorders, history of drug abuse or other behavior that requires psychiatric medication intervention; • Development of situations beyond clinical control that impede participation in aerobic training activities, exertion or group activities; • Although there is no description of serious complications in individuals submitted to LLLT, those with a history of epilepsy, seizures, heart disease, ar