Fibromyalgia (FM) is a complex, multi-symptom condition that predominantly affects women. The majority of those affected are unlikely to gain significant symptomatic control from the few treatments that are approved for FM. In this 10-week, single-blind, crossover trial we tested the immune effects of eight weeks of oral administration of low-dose naltrexone (LDN). We enrolled eight women with an average age of 46 years, symptom severity of 62 out of 100, and symptom duration of 14 years. We found that LDN was associated with reduced plasma concentrations of interleukin (IL)-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-15, IL-17A, IL-27, interferon (IFN)-α, transforming growth factor (TGF)-α, TGF-β, tumor necrosis factor (TNF)-α, and granulocyte-colony stimulating factor (G-CSF). We also found a 15% reduction of FM-associated pain and an 18% reduction in overall symptoms. The findings of this pilot trial suggest that LDN treatment in fibromyalgia is associated with a reduction of several key pro-inflammatory cytokines and symptoms. The potential role of LDN as an atypical anti-inflammatory medication should be explored further.

The purpose of this longitudinal blood sampling study was to examine relationships between sex hormones and fibromyalgia pain. Eight women meeting case definition criteria for fibromyalgia provided venous blood samples and reported their fibromyalgia pain severity over 25 consecutive days. All women exhibited normal menstrual cycles and were not taking oral contraceptives. Cortisol, and the sex hormones estradiol, progesterone, and testosterone, were assayed from serum. A linear mixed model was used to determine if fluctuations of sex hormones were associated with changes in pain severity. In the entire sample, day to day changes in progesterone (P = .002) as well as testosterone (P = .015) were significantly and inversely correlated with pain severity. There was no relationship between estradiol and pain (P = .551) or cortisol and pain (P = .633). These results suggest that progesterone and testosterone play a protective role in fibromyalgia pain severity. Sex and other hormones may serve to increase as well as decrease fibromyalgia pain severity. Sex hormones fluctuate normally in women with fibromyalgia, but may still contribute to pain severity.

Gulf War Illness (GWI) is a clinically heterogeneous chronic condition that affects many veterans of the 1990–1991 Persian Gulf War. One of the most prevalent and debilitating symptoms of GWI is abnormal fatigue. The mechanisms underlying GWI generally, and fatigue symptoms specifically, have yet to be conclusively identified, although immune system abnormalities are suspected to be involved. The first goal of this immune monitoring study was to determine if GWI is associated with higher absolute levels and daily variability of pro-inflammatory immune factors. The second goal was to explore the relationship between day-to-day immune marker fluctuations and daily self-reported fatigue severity. We recruited veterans with GWI and healthy veteran control (HV) participants to provide self-reported fatigue severity data and blood samples, over 25 consecutive days. We profiled inflammatory processes by using a longitudinal, daily immune-monitoring approach. For each day, serum cytokine and chemokine concentrations were determined using multiplex assays. Seven veterans with GWI and eight healthy veteran control (HV) participants completed the study protocol. We found that GWI was associated with higher variability in the expression of eotaxin-1 (p < 0.001). For GWI participants, higher fatigue severity days were associated with greater IL-1β (p = 0.008) and IL-15 (p < 0.001). Our findings provide preliminary evidence that the immune system is involved in the pathophysiology of GWI. Longitudinal immune profiling approaches may be helpful in discovering targets for novel therapies in conditions such as GWI.

This observational study aimed to determine whether individuals with fibromyalgia (FM) exhibit higher levels of neuroinflammation than healthy controls (HCs), as measured with positron emission tomography using [¹⁸F]DPA-714, a second-generation radioligand for the translocator protein (TSPO). Fifteen women with FM and 10 HCs underwent neuroimaging. Distribution volume (V_T) was calculated for in 28 regions of interest (ROIs) using Logan graphical analysis and compared between groups using multiple linear regressions. Group (FM vs HC) was the main predictor of interest and TSPO binding status (high- vs mixed-affinity) was added as a covariate. The FM group had higher V_T in the right postcentral gyrus (b = 0.477, P = 0.033), right occipital gray matter (GM; b = 0.438, P = 0.039), and the right temporal GM (b = 0.466, P = 0.042). The FM group also had lower V_T than HCs in the left isthmus of the cingulate gyrus (b = −0.553, P = 0.014). In the subgroup of high-affinity binders, the FM group had higher V_T in the bilateral precuneus, postcentral gyrus, parietal GM, occipital GM, and supramarginal gyrus. Group differences in the right parietal GM were associated with decreased quality of life, higher pain severity and interference, and cognitive problems. In support of our hypothesis, we found increased radioligand binding (V_T) in the FM group compared with HCs in several brain regions regardless of participants' TSPO binding status. The ROIs overlapped with prior reports of increased TSPO binding in FM. Overall, increasing evidence supports the hypothesis that FM involves microglia-mediated neuroinflammation in the brain.

Objective: Fibromyalgia (FM) is a debilitating chronic pain condition with few treatment options. Central sensitization and neuroinflammation have been forwarded as models of FM pathophysiology, both of which indicate dextromethorphan (DXM) as a potential treatment. DXM is an NMDA-receptor antagonist and microglial modulator with anti-neuroinflammatory properties at low doses. It is available for clinical use but has not been tested as a treatment for FM at low dosages. This study evaluated the effectiveness of DXM in treating FM-associated symptoms. Methods: In a single-blind, placebo-controlled trial, 14 women meeting the 2010 American College of Rheumatology criteria for FM received a placebo for five weeks, followed by 20 mg DXM for ten weeks, while providing daily symptom reports on a 0– 100 scale. Pain and physical activity were the primary and secondary outcomes, respectively. Daily symptom ratings during the last four weeks of placebo were contrasted with ratings during the last four weeks of the active treatment using generalized estimating equations (GEE). Results: DXM was well tolerated, and treatment adherence was high. Baseline pain was reduced by at least 20% in six participants. Self-reported daily pain and physical activity in the entire cohort were not significantly different between the placebo and DXM conditions, and the primary hypotheses were not supported. Exploratory analyses using the entire placebo and DXM data showed that pain was significantly lower in the DXM condition than in the placebo condition (b=− 9.933, p=0.013). Discussion: A strong clinical effect of DXM was not observed at the 20mg/day dosage.