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.

Predictive validity of general work ability assessments in the context of sickness insurance.

OBJECTIVE: The activity ability assessment is a Swedish method for assessing general work ability, based on self-reports combined with an examination by specially trained physicians, and, if needed, extended assessments by occupational therapists, physiotherapists and/or psychologists. The aim of this study was to analyse the predictive validity of the activity ability assessment in relation to future sick leave. DESIGN: Analysis of assessments in 300 case files, in relation to register data on sick leave. SUBJECTS: People on sick leave (n =300, 32% men, 68% women; mean age 48 years; assessment at mean sick leave day 249). METHODS: Univariate and multivariate statistics. RESULTS: Self-rated work ability was the only factor with predictive value related to future sick leave. Physicians' evaluations lacked predictive value, except where the person had a limitation in vision, hearing or speech that was predictive of future decisions by the Social Insurance Agency. No sex differences were identified. CONCLUSION: The predictive value of the activity ability assessment for future sick leave is limited, and self-rated work ability is more accurate compared with an extensive insurance medical assessment. Self-rated work ability may be more holistic compared with insurance medicine assessments, which may be overly focused on individual factors. A practical implication of this is that the inclusion of contextual factors in assessment procedures needs to be improved.

Resistance exercise improves muscle strength, health status and pain intensity in fibromyalgia--a randomized controlled trial.

INTRODUCTION: Fibromyalgia (FM) is characterized by persistent widespread pain, increased pain sensitivity and tenderness. Muscle strength in women with FM is reduced compared to healthy women. The aim of this study was to examine the effects of a progressive resistance exercise program on muscle strength, health status, and current pain intensity in women with FM. METHODS: A total of 130 women with FM (age 22-64 years, symptom duration 0-35 years) were included in this assessor-blinded randomized controlled multi-center trial examining the effects of progressive resistance group exercise compared with an active control group. A person-centred model of exercise was used to support the participants' self-confidence for management of exercise because of known risks of activity-induced pain in FM. The intervention was performed twice a week for 15 weeks and was supervised by experienced physiotherapists. Primary outcome measure was isometric knee-extension force (Steve Strong®), secondary outcome measures were health status (FIQ total score), current pain intensity (VAS), 6MWT, isometric elbow-flexion force, hand-grip force, health related quality of life, pain disability, pain acceptance, fear avoidance beliefs, and patient global impression of change (PGIC). Outcomes were assessed at baseline and immediately after the intervention. Long-term follow up comprised the self-reported questionnaires only and was conducted after 13-18 months. Between-group and within-group differences were calculated using non-parametric statistics. RESULTS: Significant improvements were found for isometric knee-extension force (p = 0.010), health status (p = 0.038), current pain intensity (p = 0.033), 6MWT (p = 0.003), isometric elbow flexion force (p = 0.02), pain disability (p = 0.005), and pain acceptance (p = 0.043) in the resistance exercise group (n = 56) when compared to the control group (n = 49). PGIC differed significantly (p = 0.001) in favor of the resistance exercise group at post-treatment examinations. No significant differences between the resistance exercise group and the active control group were found regarding change in self-reported questionnaires from baseline to 13-18 months. CONCLUSIONS: Person-centered progressive resistance exercise was found to be a feasible mode of exercise for women with FM, improving muscle strength, health status, and current pain intensity when assessed immediately after the intervention. TRIAL REGISTRATION: ClinicalTrials.gov identification number: NCT01226784, Oct 21, 2010.

Different patterns of blood flow response in the trapezius muscle following needle stimulation (acupuncture) between healthy subjects and patients with fibromyalgia and work-related trapezius myalgia.

Needle stimulation (acupuncture) has recently been shown to increase blood flow in the tibialis anterior muscle and overlying skin in healthy subjects (HS) and patients with fibromyalgia (FM). The aim of the present study was to examine the effect of needle stimulation on local blood flow in the trapezius muscle and overlying skin in HS and two groups of patients suffering from chronic pain in the trapezius muscle, i.e., FM and work-related trapezius myalgia (TM) patients. Two modes of needling, deep muscle stimulation (Deep) and subcutaneous needle insertion (SC), were performed at the upper part of the shoulder and blood flow was monitored for 60 min post-stimulation. Blood flow changes were measured non-invasively by using a new application of photoplethysmography. Increased blood flow in the trapezius muscle and overlying skin was found in all three groups following both Deep and SC. In HS, Deep was superior to SC in increasing skin and muscle blood flow, whereas in FM, SC was as effective as, or even more effective, than Deep. In the severely affected TM patients, no differences were found between the stimuli, and generally, a lesser blood flow response to the stimuli was found. At Deep, the muscle blood flow increase was significantly larger in HS, compared to the two patient groups. Positive correlations were found between muscle blood flow at Deep and pressure pain threshold in the trapezius muscle, neck movement and pain experienced at the stimulation, and negative correlations were found with spontaneous pain-related variables, symptom duration and age, pointing to less favorable results with worsening of symptoms, and to the importance of nociceptor activation in blood flow increase. It was hypothesized that the different patterns of muscle blood flow response to the needling may mirror a state of increased sympathetic activity and a generalized hypersensitivity in the patients. The intensity of stimulation should be taken into consideration when applying local needle stimulation (acupuncture) in order to increase the trapezius muscle blood flow in chronic pain conditions.

Peripheral effects of needle stimulation (acupuncture) on skin and muscle blood flow in fibromyalgia.

Acupuncture has become a widely used treatment modality in various musculoskeletal pain conditions. Acupuncture is also shown to enhance blood flow and recovery in surgical flaps. The mechanisms behind the effect on blood flow were suggested to rely on vasoactive substances, such as calcitonin gene-related peptide, released from nociceptors by the needle stimulation. In a previous study on healthy subjects, one needle stimulation into the anterior tibial muscle was shown to increase both skin and muscle blood flow. The aim of this study was to examine the effect of needle stimulation on local blood flow in the anterior tibial muscle and overlying skin in patients suffering from a widespread chronic pain condition. Fifteen patients with fibromyalgia (FM) participated in the study. Two modes of needling, deep muscle stimulation and subcutaneous needle insertion were performed at the upper anterior aspect of the tibia, i.e., in an area without focal pathology or ongoing pain in these patients. Blood flow changes were assessed non-invasively by photoplethysmography (PPG). The results of the present study were partly similar to those earlier found at a corresponding site in healthy female subjects, i.e., deep muscle stimulation resulted in larger increase in skin blood flow (mean (SE)): 62.4% (13.0) and muscle blood flow: 93.1% (18.6), compared to baseline, than did subcutaneous insertion (mean (SE) skin blood flow increase: 26.4% (6.2); muscle blood flow increase: 46.1% (10.2)). However, in FM patients subcutaneous needle insertion was followed by a significant increase in both skin and muscle blood flow, in contrast to findings in healthy subjects where no significant blood flow increase was found following the subcutaneous needling. The different results of subcutaneous needling between the groups (skin blood flow: p=0.008; muscle blood flow: p=0.027) may be related to a greater sensitivity to pain and other somatosensory input in FM.

Effects of acupuncture on skin and muscle blood flow in healthy subjects.

In 14 healthy female subjects, the effects of needle stimulation (acupuncture) on skin and muscle blood flow were investigated using a non-invasive custom-designed probe and photoplethysmography (PPG). In randomised order, 2-7 days apart, three modes of needle stimulation were performed on the anterior aspect of the tibia: superficial insertion (SF), insertion into the anterior tibial muscle (Mu), and insertion into the muscle including manipulation of the needle in order to elicit a distinct sensation of distension, heaviness or numbness (DeQi). Before intervention, the subjects rested for 30 min. After the intervention, the needle was left in situ for 20 min. Blood flow recordings were performed intermittently from 10 min prior to the intervention to the end of the trial. In a fourth session, serving as control, corresponding measurements were performed without any needle stimulation. Area under curve was calculated for 5-min periods prior to and after stimulation, respectively, and for the remaining 15-min period after stimulation. Compared to the control situation, muscle blood flow increased following both Mu and DeQi for 20 min, with the latter being more pronounced for the initial 5 min. Skin blood flow increased for 5 min following DeQi. However, no increase was found following SF. The DeQi stimulation was preceded by higher visual analogue scale ratings of anxiety prior to stimulation, which might have influenced skin blood flow to some extent. The results indicate that the intensity of the needling is of importance, the DeQi stimulation resulting in the most pronounced increase in both skin and muscle blood flow.