Coenzyme Q10 supplementation in rheumatic diseases: A systematic review.

Coenzyme Q10 (CoQ10) is a potent antioxidant and anti-inflammatory substance used to treat some rheumatic diseases. Our objective was to review the use of CoQ10 in rheumatic diseases. PubMed/Medline, Embase, Scopus, and Web of Science databases were searched for articles on CoQ10 and rheumatic diseases between 1966 and April 2023. Twenty articles were found, including 483 patients. The investigated conditions were Fibromyalgia (FM) with 15 studies, Rheumatoid Arthritis (RA) with 3 studies, and Antiphospholipid Syndrome (APS) with 2 studies. After CoQ10 supplementation, RA patients observed improvements in disease activity index, inflammatory biomarkers (erythrocyte sedimentation rate), cytokine levels, and a decrease in malondialdehyde. In APS, CoQ10 improved endothelial function and decreased prothrombotic and proinflammatory mediators. Regarding FM, in most of the studies, the patients observed improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire (FIQ). The drug was well tolerated, with reports of minor side effects in two studies. CoQ10 supplementation seems to be efficacious as a complementary treatment for RA and FM. Upcoming studies with larger samples and including other rheumatic diseases are welcome.

Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview.

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown causes characterised by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS); fibromyalgia (FM); and more recently post-COVID-19 condition (long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders. Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. The accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and long COVID. To address this issue, this article aims to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, it aims to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.

Intramuscular injections of botulinum toxin for the treatment of upper back myofascial pain syndrome: A systematic review of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Myofascial pain syndrome (MPS) is a chronic musculoskeletal disorder characterized by the presence of trigger points. Among the treatment options, botulinum toxin injections have been investigated. The aim of this paper was to provide a synthesis of the evidence on intramuscular botulinum toxin injections for upper back MPS. DATABASES AND DATA TREATMENT: A systematic review of the literature was performed on the PubMed, Scopus and Cochrane Library, using the following formula: ("botulinum") AND ("musculoskeletal") AND ("upper back pain") OR ("myofascial pain"). RESULTS: Ten studies involving 651 patients were included. Patients in the control groups received placebo (saline solution) injections, anaesthetic injections + dry needling or anaesthetic injections. The analysis of the trials revealed modest methodological quality: one "Good quality" study, one "Fair" and the other "Poor". No major complications or serious adverse events were reported. Results provided conflicting evidence and did not demonstrate the superiority of botulinum toxin over comparators. Most of the included trials were characterized by a small sample size, weak power analysis, different clinical scores used and non-comparable follow-up periods. Even if there is no conclusive evidence, the favourable safety profile and the positive results of some secondary endpoints suggest a potentially beneficial action in pain control and quality of life. CONCLUSION: The currently available studies show conflicting results. Their overall low methodological quality does not allow for solid evidence of superiority over other comparison treatments. Further insights are needed to properly profile patients who could benefit more from this peculiar injective approach. SIGNIFICANCE: The randomized controlled trials included in this review compared using botulinum toxin to treat upper back MPS with placebo or active treatments (e.g., dry needling or anaesthetics) showing mixed results overall. Despite the lack of clear evidence of superiority, our study suggests that the use of botulinum toxin should not be discouraged. Its safety profile and encouraging results in pain control, motor recovery and disability reduction make it an interesting treatment, particularly in the subset of patients with moderate to severe chronic pain and active trigger points. To support the safety and efficacy of botulinum toxin, further high-quality studies are needed.

The effect of vitamin D treatment on quality of life in patients with fibromyalgia.

BACKGROUND: Fibromyalgia is a syndrome characterized by chronic widespread pain accompanied by fatigue, disrupted sleep quality, cognitive impairments, subjective soft tissue swelling, and somatic symptoms. There are conflicting results in the literature regarding the prevalence of vitamin D deficiency in fibromyalgia patients and the reduction of symptoms after supplementation. AIMS: Our study aims to evaluate the effectiveness and reliability of vitamin D supplementation in patients diagnosed with fibromyalgia. METHODS: In our cross-sectional clinical study, 180 female patients aged 18 to 65 diagnosed with fibromyalgia according to the 2010 American College of Rheumatology Diagnostic Criteria were included. Oral vitamin D3 replacement of 50,000 IU was administered for 12 weeks. Patients' Fibromyalgia Impact Questionnaire (FIQ)and Visual Analogue Scale (VAS) scores were evaluated before and after the study. RESULTS: Significant differences were observed in the FIQ scores of the 180 fibromyalgia patients before and after vitamin D supplementation (p < 0.05). There was also a significant improvement in VAS scores (p < 0.01). A negative correlation between vitamin D and VAS as well as FIQ scores was found in the study. CONCLUSION: We determined that vitamin D deficiency is significantly more prevalent in patients diagnosed with fibromyalgia. Vitamin D supplementation was observed to have a positive effect on quality of life and reduction of pain.

Green Light-Based Analgesia - Novel Nonpharmacological Approach to Fibromyalgia Pain: A Pilot Study.

BACKGROUND: There continues to be significant reliance on pharmacological modalities for the management of chronic pain, with a particular focus on opioid analgesics as a singular option for pain management. Fibromyalgia is a prototypical central pain disorder, which is often used as a model to study chronic pain disorders. It has an estimated prevalence of approximately 1.1% to 5.4% in the general population. The widespread use of opioids in patients with fibromyalgia has been well demonstrated in several health claims database studies, with rates of use ranging from 11.3% to 69%. Minimizing opioid exposures reduces misuse risk, but requires adequate opioid-sparing multimodal analgesic strategies, particularly nonopioid analgesic adjuncts, to ensure effective treatment of pain, particularly high-impact pain. We chose fibromyalgia as our study population. Given that it is a disordered sensory processing condition, it may be particularly amenable to the beneficial effects of green-light therapy. OBJECTIVES: Most studies have evaluated exposure to light-emitting diode lights as a mode of green-light delivery; our study used green-light filtering eyeglasses, which would allow the wearer to move about with minimal interference. STUDY DESIGN: We conducted a randomized controlled trial to test the feasibility of green-light filtering eyeglasses in the treatment of chronic pain. SETTING: This study was conducted at Duke University Health System. METHODS: We recruited and randomized adult patients with a known diagnosis of fibromyalgia patients and excluded patients who were unable to wear eyeglasses for at least 4 hours per day or were colorblind according to the Ishihara Colorblindness Test. Patients were assigned to 1 of 3 arms: clear eyeglasses (control), green eyeglasses, or blue eyeglasses. We initially recruited 45 patients and randomly assigned 15 patients per group. RESULTS: To evaluate clinical significance, we determined the rate of >= 10% decline in oral morphine equivalents and found that 33%, 11%, and 8% of the green, blue, and clear eyeglass groups, respectively, achieved this clinically meaningful outcome. LIMITATIONS: This study was powered to detect feasibility of the intervention, rather than conclusive analgesic effects. CONCLUSIONS: Our study demonstrated the feasibility of this treatment approach and study design and supports a future study to determine the efficacy of green light-based analgesia on opioid use, pain, and anxiety. While the reduction of opioid use was not of statistical significance, we believe it to be of clinical significance as there was no increase of patient-reported pain. This warrants further investigation in a large-scale trial of the use of green-light filtration of ambient light to mitigate opioid use and possible mediation of psychological impacts of pain with the use of green-lensed eyeglasses.

Acupoint Catgut Embedding Diminishes Fibromyalgia Pain through TRPV1 in the Mouse Brain.

BACKGROUND: Chronic pain refers to pain that persists for over three months. Chronic pain may restrict activities of daily living, including work, learning, social life, and can lead to anxiety, depression, and sleep disturbance. Imaging data have demonstrated that central sensitization often occurs in the brain of patients with chronic pain, which arises from imbalanced neurotransmission in the central nervous system. Transient receptor potential vanilloid 1 (TRPV1) is an ion channel to serve as an inflammatory detector in the brain. We aim to determine the properties of acupoint catgut embedding (ACE) on cold stress-induced mice fibromyalgia (FM) and surveyed the character of TRPV1 and linked molecules in chronic FM pain. METHODS: Intermittent cold stress (ICS) was used to induce mice FM model. Mice were subgrouped into normal mice, ICS-induced FM group, FM mice with ACE, and FM in Trpv1-⁣/- group. ACE is a novel acupuncture technique that provides convenience and continuous nerve stimulation that has been reported effective on pain management. RESULTS: Our behavioral experiments showed similar levels of pain response among all groups before treatment. After ICS, prolonged mechanical and thermal pain was initiated (mechanical threshold: 1.96 ± 0.12 g; thermal latency: 4.86 ± 0.21 s) and were alleviated by ACE treatment and TRPV1 gene deletion. Inflammatory mediators were increased in the plasma of FM mice, while TRPV1 and related kinases were amplified in the hypothalamus and cerebellum. These changes were ameliorated in the ACE-treated and Trpv1-⁣/- groups. CONCLUSIONS: These novel findings suggest that chronic FM pain can be modulated by ACE or TRPV1 gene deletion. The analgesic effect of ACE through the TRPV1 pathway may reflect its potential as a therapeutic target for FM treatment.

Racial Disparities in Pain Among Women with Fibromyalgia: Secondary Data Analysis of Severity, Interference with Function, and Response to Guided Imagery.

Background: Fibromyalgia syndrome (FMS) is characterized by widespread persistent musculoskeletal pain. Mostly prevalent among White women, little is known about FMS in other population cohorts. This study examined secondary data of a racially diverse sample of women with FMS that were collected as part of a randomized controlled clinical trial that examined the effect of a complementary therapy intervention over the course of a 10-week guided imagery intervention to identify demographic, social, or economic differences in self-reported pain. Materials and Methods: The Brief Pain Inventory (BPI), which measures pain severity and interference, was administered to 72 women (21 Black and 51 Whites) at baseline, 6 and 10 weeks. Student's t tests and time series regression models examined racial difference in pain dimensions and treatment response. Regression models accounted for age, race, income, duration of symptoms, treatment group, pain at baseline, smoking, alcohol use, comorbid conditions, and time. Results: Black women experienced significantly higher pain severity (ß = 5.52, standard deviation [SD] = 2.13) and interference (ß = 5.54, SD = 2.74) than Whites (severity ß = 4.56, SD = 2.08; interference ß = 4.72, SD = 2.76) (interference: t = 1.92, p = 0.05; severity: t = 2.95, p = 0.00). Disparities persisted over time. Controlling for differences in age, income, and previous pain levels, Black women had 0.26 (standard error [SE] = 0.065) higher pain severity and 0.36 (SE = 0.078) higher interference than Whites. Low-income earners also experienced 2.02 (SE = 0.38) and 2.19 (SE = 0.46) higher pain severity and interference, respectively, than other earners. Results were robust to inclusion of comorbidities. Conclusions: Black women and low-income earners experienced significantly higher levels of pain severity and interference and a lower dose response to the intervention. Differentials were robust to inclusion of demographic, health, and behavioral characteristics. Findings suggest that external factors may contribute to pain perception among women with FMS.

Palmitoylethanolamide and acetyl-L-carnitine act synergistically with duloxetine and pregabalin in fibromyalgia: results of a randomised controlled study.

OBJECTIVES: Fibromyalgia (FM) is characterised by a form of debilitating pain that is unresponsive to standard analgesics. The aim of this study was to evaluate the efficacy of supplementing ongoing pregabalin (PGB) and duloxetine (DLX) treatment with palmitoylethanolamide (PEA) and acetyl-L-carnitine (ALC) for 24 weeks in FM patients. METHODS: After undergoing three months of stable treatment with DLX+PGB, FM patients were randomised to continue the same treatment (Group 1) or to add PEA 600 mg b.i.d + ALC 500 mg b.i.d. (Group 2) for a further 12 weeks. Every two weeks throughout the study, cumulative disease severity was estimated using the Widespread Pain Index (WPI) as the primary outcome measure; the secondary outcomes were the fortnightly scores of the patient-completed revised Fibromyalgia Impact Questionnaire (FIQR) and the modified Fibromyalgia Assessment Status (FASmod) questionnaire. All three measures were expressed as time-integrated area under the curve (AUC) values. RESULTS: One hundred and thirty (91.5%) of the initial 142 FM patients completed the study: 68 patients in Group 1 and 62 in Group 2. Twenty-four weeks after randomisation, the Group 2 patients showed additional significant improvements in all three outcome measures. Although there was some fluctuation in both groups during the study period, the AUC values of the WPI scores steadily decreased in Group 2 (p=0.048), which also showed better outcomes in terms of the AUC values of the FIQR (p=0.033) and FASmod scores (p=0.017). CONCLUSIONS: This is the first randomised controlled study demonstrating the effectiveness of the adding on therapy of PEA+ALC to DLX+PGB in FM patients.

Melatonin supplementation improves rheumatological disease activity: A systematic review.

BACKGROUND: Melatonin is a pineal hormone with a complex role. It is linked to sleep, inflammatory, oxidative, and immunological processes. AIM: To review the use of melatonin supplementation in rheumatological diseases. METHODS: A systematic search of PubMed, Embase, and Scielo databases was performed, looking for articles on Melatonin and rheumatic diseases published between 1966 and August 2022. RESULTS: Thirteen articles were identified: in fibromyalgia (n = 5 articles), rheumatoid arthritis (n = 2), systemic sclerosis (n = 1), systemic lupus erythematosus (n = 1) and osteoporosis/osteopenia (n = 3) and osteoarthritis (n = 1). There were positive results of melatonin administration in fibromyalgia, osteoarthritis, and osteoporosis/osteopenia but not in rheumatoid arthritis and lupus. The drug was well tolerated with mild side effects. CONCLUSION: This review shows the efficacy of Melatonin in some rheumatic diseases. However, new studies are needed to elucidate the real role of this treatment in rheumatology.

Predicting acupuncture efficacy in fibromyalgia: results of a pragmatic open-label study.

OBJECTIVES: To identify the predictive factors of treatment response to acupuncture in patients with fibromyalgia (FM). METHODS: Patients with FM refractory to standard drug therapy underwent eight weekly acupuncture sessions. Significant improvement, defined as a reduction of at least 30% of the revised Fibromyalgia Impact Questionnaire (FIQR), was assessed at the end of the eight weeks (T1) of treatment and three months after the end of treatment (T2). Univariate analysis was conducted to identify predictors of significant improvement at T1 and T2. Variables that resulted to be significantly associated with clinical improvement at univariate analysis were included in multivariate models. RESULTS: Analyses were conducted on 77 patients (9 males, 11.7%). At T1, significant improvement in FIQR was recorded in 44.2% of patients. At T2, persistent significant improvement was recorded in 20.8% of patients. In the multivariate analysis, predictive variables of treatment failure were tender point count (TPC) (odds ratio [OR] =0.49, 95% confidence interval [95% CI]: 0.28-0.86, p=0.01) and pain magnification (OR=0.68, 95% CI: 0.47-0.99, p=0.04) assessed with the Pain Catastrophising Scale, at T1. At T2, the only predictive variable of treatment failure was concomitant duloxetine use (OR=0.21, 95% CI: 0.05-0.95, p=0.04). CONCLUSIONS: High TPC and a tendency for pain magnification predict immediate treatment failure, while duloxetine therapy predicts it three months after completion of the acupuncture course. The identification of clinical characteristics of unfavourable response to acupuncture could help to implement a cost-effective prevention of treatment failure in FM.

Combination analgesic development for enhanced clinical efficacy (the CADENCE trial): a double-blind, controlled trial of an alpha-lipoic acid-pregabalin combination for fibromyalgia pain.

ABSTRACT: Drug therapy for fibromyalgia is limited by incomplete efficacy and dose-limiting adverse effects (AEs). Combining agents with complementary analgesic mechanisms-and differing AE profiles-could provide added benefits. We assessed an alpha-lipoic acid (ALA)-pregabalin combination with a randomized, double-blind, 3-period crossover design. Participants received maximally tolerated doses of ALA, pregabalin, and ALA-pregabalin combination for 6 weeks. The primary outcome was daily pain (0-10); secondary outcomes included Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events, and other measures. The primary outcome of daily pain (0-10) during ALA (4.9), pregabalin (4.6), and combination (4.5) was not significantly different ( P = 0.54). There were no significant differences between combination and each monotherapy for any secondary outcomes, although combination and pregabalin were both superior to ALA for measures of mood and sleep. Alpha-lipoic acid and pregabalin maximal tolerated doses were similar during combination and monotherapy, and AEs were not frequent with combination therapy. These results do not support any additive benefit of combining ALA with pregabalin for fibromyalgia. The observation of similarly reached maximal tolerated drug doses of these 2 agents (which have differing side-effect profiles) during combination and monotherapy-without increased side effects-provides support for future development of potentially more beneficial combinations with complementary mechanisms and nonoverlapping side effects.

Efficacy of mecobalamin (vitamin B12) in the treatment of long-term pain in women diagnosed with fibromyalgia: protocol for a randomised, placebo-controlled trial.

INTRODUCTION: Fibromyalgia causes long-term pain. It affects at least 2% of the population, the majority being women. In addition, extended symptoms corresponding to vitamin B12 deficiency occur. Findings from several studies have indicated that vitamin B12 may be a possible treatment for pain in fibromyalgia. The aim of the proposed study is to evaluate whether vitamin B12 decreases pain sensitivity and the experience of pain (ie, hyperalgesia and allodynia) in women with fibromyalgia. METHODS AND ANALYSIS: The study is a randomised, placebo-controlled, single-blind, clinical trial with two parallel groups which are administered mecobalamin (vitamin B12) or placebo over 12 weeks. 40 Swedish women aged 20-70 years with an earlier recorded diagnosis of fibromyalgia are randomised into the placebo group or the treatment group, each consisting of 20 participants. Outcomes consist of questionnaires measured at baseline and after 12 weeks of treatment. A final re-evaluation will then follow 12 weeks after treatment ends. The primary outcome is tolerance time, maximised to 3 min, which is assessed using the cold pressor test. In order to broaden the understanding of the lived experience of participants, qualitative interviews will be conducted using a phenomenological approach on a lifeworld theoretical basis (reflective lifeworld research approach). ETHICS AND DISSEMINATION: The protocol for the study is approved by the local ethical committee at Linkoping (EPM; 2018/294-31, appendices 2019-00347 and 2020-04482). The principles of the Helsinki Declaration are followed regarding oral and written consent to participate, confidentiality and the possibility to withdraw participation from the study at any time. The results will primarily be communicated through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: NCT05008042.

Stress-associated weight gain, fibromyalgia symptoms, cardiometabolic markers, and human growth hormone suppression respond to an amino acid supplement blend: Results of a prospective, cohort study.

Introduction: An orally administered amino acid-based test supplement was recently shown to increase human growth hormone (hGH) in healthy adults. This prospective, observational, single-center, single-arm cohort study investigated the effects of 24 weeks of daily oral administration of the test supplement in individuals with stress-related weight gain, fibromyalgia (FM) and stress-related low-normal hGH production (15-30th percentile for age-appropriate levels) on insulin-like growth factor 1 (IGF-1), an indicator of hGH levels caused by stress related stimulation of somatostatin. Methods: Participants continued to receive standard care. The primary endpoint was the change from baseline to endpoint (Week 24) in serum IGF-1. Additional endpoints included the change in body weight, clinical symptoms (assessed with the Revised Fibromyalgia Impact Questionnaire [FIQR], range 0-100, and Perceived Stress Scale [PSS], range 0-40), fasting cardiometabolic markers, tolerability, and safety. The study enrolled 84 fibromyalgia patients with low-normal age-adjusted IGF-1 serum levels. High mean ± Standard Deviation (SD) baseline FIQR and PSS scores of 76 ± 16 and 32 ± 5, respectively, indicated poor to moderate symptom management with standard care. All individuals completed 24 weeks. Results: Serum IGF-1 levels increased with a Week 24 mean± Standard Error (SE) change of 28.4 ± 3.0 ng/mL (p<0.001). Body weight was reduced with a Week 24 mean ± SE change of -5.5 ± 0.3 kg (p<0.001) (a 6.5% weight loss from baseline). The change from baseline in FIQR and PSS scores were -29.1 ± 1.1 and -20.0 ± 0.8, respectively (both p<0.001), indicating a substantial improvement. Statistically significant improvements from baseline to Week 24 were observed in systolic and diastolic blood pressure, HbA1c, LDL and HDL cholesterol, and triglycerides (all p<0.001). The supplement was well tolerated; no adverse events were reported. Discussion: Sustained augmentation of IGF-1 with the test supplement may represent a novel method of improving clinical symptoms, including stress-related weight gain, in individuals with fibromyalgia and stress-associated low-normal hGH.

Effectiveness of aquatic therapy on sleep in persons with fibromyalgia. A meta-analysis.

CONTEXT: Fibromyalgia syndrome (FMS) is a chronic musculoskeletal condition characterized by persistent, widespread pain, myofascial tenderness, negative affect, fatigue, memory problems and sleep disturbances. OBJECTIVE: To summarize the evidence of the effects of aquatic therapy on sleep quality in patients with FMS. METHODS: This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2020 (PRISMA) guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO), whit the registration number CRD42021249982. Cochrane library, Medline (PubMed), Science Direct Web of Science (WOS), Scopus, and PEDro were searched from inception until September 2021. The search included only randomized clinical trials. RESULTS: Of the 7711 studies identified in the initial search, a total of 7 trials (361 participants) satisfied the eligibility criteria. Finally, a meta-analysis was conducted with 6 studies (311 participants). The overall pooled effect favored aquatic therapy interventions in improving sleep quality in patients with FMS (pooled MD, -2.05; 95% CI, -4.35 to 0.25). CONCLUSIONS: The results of this systematic review and meta-analysis provide evidence that aquatic therapy improved sleep quality in patients with FMS. This study highlights the importance of aquatic therapy for sleep. Nonetheless, although an aquatic therapy intervention may represent a good option to improve sleep, given the low number of studies the evidence should be taken with caution.

Cannabis-opioid interaction in the treatment of fibromyalgia pain: an open-label, proof of concept study with randomization between treatment groups: cannabis, oxycodone or cannabis/oxycodone combination-the SPIRAL study.

BACKGROUND: Opioids continue to be widely prescribed for chronic noncancer pain, despite the awareness that opioids provide only short-time pain relief, lead to dose accumulation, have numerous adverse effects, and are difficult to wean. As an alternative, we previously showed advantages of using pharmaceutical-grade cannabis in a population of chronic pain patients with fibromyalgia. It remains unknown whether combining an opioid with pharmaceutical-grade cannabis has advantages, such as fewer side effects from lesser opioid consumption in chronic pain. METHODS: Trial design: a single-center, randomized, three-arm, open-label, exploratory trial. Trial population: 60 patients with fibromyalgia according to the 2010 definition of the American College of Rheumatologists. INTERVENTION: Patients will be randomized to receive up to 4 daily 5 mg oral oxycodone sustained release (SR) tablet, up to 5 times 150 mg inhaled cannabis (Bediol®, containing 6.3% Δ9-tetrahydrocannabinol and 8% cannabidiol), or the combination of both treatments. Treatment is aimed at self-titration with the daily maximum doses given. Treatment will continue for 6 weeks, after which there is a 6-week follow-up period. Main trial endpoint: The number of side effects observed during the course of treatment using a composite adverse effect score that includes the following 10 symptoms: dizziness (when getting up), sleepiness, insomnia, headache, nausea, vomiting, constipation, drug high, hallucinations, and paranoia. Secondary and tertiary endpoints include pain relief and number of oxycodone doses and cannabis inhalations. DISCUSSION: The trial is designed to determine whether self-titration of oxycodone and cannabis will reduce side effects in chronic pain patients with fibromyalgia. TRIAL REGISTRATION {2A AND 2B}: EU trial register 2019-001861-33, URL https://www.clinicaltrialsregister.eu , on July 17, 2019; World Health Organization International Clinical Trials Research Platform NL7902, URL https://trialsearch.who.int , on July 26, 2019.

Efficacy of ozone therapy as an add-on treatment in fibromyalgia: A randomized double-blind placebo-controlled study.

BACKGROUND: Fibromyalgia (FM) is a chronic disease that causes widespread pain, fatigue, and sleep disturbance. There is still no effective definitive treatment method; therefore, the search for treatment continues. OBJECTIVE: The purpose of this study is to investigate the effectiveness of ozone therapy (OT), which has been used in FM treatment in recent years, as an additional treatment. METHODS: The patients were divided into OT (n= 26) and placebo control (PC) (n= 28) groups. Both groups received OT in the form of major autohemotherapy (MaAHT) and minor autohemotherapy (MiAHT) for two sessions per week for a total of 10 sessions. The fibromyalgia impact questionnaire (FIQ), Pittsburgh sleep quality index (PSQI), and 12-item short-form health survey (SF-12) were used for evaluation pre- and post-intervention. RESULTS: In the between-group comparison, the OT group showed significant post-treatment improvements in FIQ subscales (feel good, fatigue) and PSQI total score and subscales (subjective sleep quality, sleep latency and sleep disturbances) compared to the PC group (p< 0.05). Although there were improvements in the FIQ total score post-treatment in both groups, there was no significant difference between the groups (p>0.05). CONCLUSION: OT, which is applied as an additional treatment with the autohemotherapy method, simultaneously improves the subscale scores (feel good and fatigue) of FM and sleep quality in the treatment period. However, changes in the post-treatment FIQ total score were not different in the ozone therapy group from the placebo control group.

The role of cannabis in treatment-resistant fibromyalgia women.

BACKGROUND: Fibromyalgia is a complex pain-focused syndrome. Previous studies showed that Cannabis is efficacious in promoting sleep, deepening and lengthening the sleep cycle, and good pain relief (compared with the SSRIs and SNRIs). PURPOSE: This study aimed to use the World Health Organization Quality of Life Bref questionnaire (WhoQoL-bref) to characterize the impact of Cannabis Treatment initiation on the quality of life in women suffering from treatment-resistant fibromyalgia. METHODS: A prospective cohort study involving 30 women aged 18-70 years old diagnosed with fibromyalgia, exhausted pharmacological fibromyalgia treatment, and started Cannabis treatment. Pregnant women were excluded. WhoQoL-bref was filled before Cannabis treatment initiation and 1 month following treatment. RESULTS: Women's average age was 46 years (±5), with a poor general quality of life (1.47 ± 0.63), poor general health (1.47 ± 0.78), pain and discomfort, and dependence on medication (3.77 ± 1.3 and 3.07 ± 1.74, respectively) prior to Cannabis intervention. Cannabis treatment for 30 days showed a marked improvement in general quality of life (1.97 scores, p < 0.01), general health (1.83, p < 0.01), physical health (1.5, p < 0.01), and psychological domain (1.3, p < 0.01). Financial resources and home environment were not influenced by cannabis treatment (p = 0.07, p = 0.31, respectively). CONCLUSION: Results suggest a potentially significant role of Cannabis in treatment-resistant Fibromyalgia women. Early Cannabis treatment may result in a beneficial short-term effect on the quality of life through its influence on pain, sleep, and physical and psychological domains. Further studies are still indicated to understand this potential and its long-term beneficial impact.

The Efficacy of Vitamin D Supplementation in the Treatment of Fibromyalgia Syndrome and Chronic Musculoskeletal Pain.

Fibromyalgia syndrome (FMS) and chronic widespread musculoskeletal pain (CMP) are diffuse suffering syndromes that interfere with normal activities. Controversy exists over the role of vitamin D in the treatment of these diseases. We carried out a systematic literature review of randomized controlled trials (RCT) to establish whether vitamin D (25OHD) deficiency is more prevalent in CMP patients and to assess the effects of vitamin D supplementation in pain management in these individuals. We searched PubMed, Physiotherapy Evidence Database (PEDro), and the Cochrane Central Register of Controlled Trials (CENTRAL) for RCTs published in English from 1 January 1990 to 10 July 2022. A total of 434 studies were accessed, of which 14 satisfied the eligibility criteria. In our review three studies, of which two had the best-quality evidence, a correlation between diffuse muscle pain and 25OHD deficiency was confirmed. Six studies, of which four had the best-quality evidence, demonstrated that appropriate supplementation may have beneficial effects in patients with established blood 25OHD deficiency. Eight studies, of which six had the best-quality evidence, demonstrated that 25OHD supplementation results in pain reduction. Our results suggest a possible role of vitamin D supplementation in alleviating the pain associated with FMS and CMP, especially in vitamin D-deficient individuals.

Effect of vitamin B6 on pain, disease severity, and psychological profile of fibromyalgia patients; a randomized, double-blinded clinical trial.

BACKGROUND: Given the role of vitamin B6 on pronociceptive/antinociceptive neurotransmitters balance, metabolic reactions, and inflammation, it is important to clarify the effect of vitamin B6 on pain and psychological disturbance in fibromyalgia (FM). This study aimed to evaluate whether an 80-mg daily dose of vitamin B6 improves pain, disease severity and psychological symptoms of FM compared to a placebo. METHODS: This randomized, double-blinded, placebo-controlled trial was performed on the FM patients whose diagnosis was confirmed by a rheumatologist based on the 2016 American College of Rheumatology (ACR). 90 Patients were randomized to receive either vitamin B6 (80 mg daily) or placebo in a 1:1 ratio, with a permuted block size of 30 stratified by disease severity. Primary outcomes included the Revised Fibromyalgia Impact Questionnaire (FIQR), Hospital Anxiety and Depression Scale (HADS), 12-item short-form health survey (SF-12), and pain visual analog scale (pain-VAS)). The mean differences in outcomes (before and after treatment) were compared between the vitamin B6 and placebo groups using an independent T-test. An ANCOVA model adjusted for baseline outcome value was also provided to compare the outcomes between the two groups. RESULTS: Of 90 eligible patients, 60 patients (31 patients in vitamin B6 and 29 in the placebo group) completed the trial. Overall, the FIQR, pain-VAS, and HADS-anxiety scores improved after treatment in both vitamin B6 and placebo groups; However, there was no statistically significant intergroup difference regarding primary outcomes. ANCOVA model also showed no difference in the treatment effects. CONCLUSIONS: Our results showed no priority for vitamin B6 over placebo in FM patients. Considering the potential ameliorating role of vitamin B6 on pain and psychological symptoms, acknowledgment of vitamin B6 as a relatively safe adjuvant treatment needs larger future studies. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT20200920048782N2 on 2021/10/04.