Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants ( F (1,63) = 12.8, p < 0.001), with leptin predicting ∼49% of the pain variance. In Study 2, the relationship between leptin and body pain was examined in a retrospective cross-sectional analysis of 5676 generally healthy postmenopausal women from the Women's Health Initiative. Leptin levels obtained from single blood draws were tested for a relationship with self-reported body pain. Body mass index (BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain ( p = 0.001 and p < 0.001, respectively), with higher leptin levels and greater BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia.

A chronic multi-symptom illness of unknown etiology, Gulf War Illness (GWI) affects 175,000 to 250,000 veterans of the Gulf War. Because inflammation has suspected involvement in the pathophysiology of GWI, botanical treatments that target inflammation may be beneficial in reducing symptoms. No FDA-approved treatments currently exist for GWI, and rapid prioritization of agents for future efficacy testing is important. This study is part of a larger project that screened nine different botanical compounds with purported anti-inflammatory properties for potential treatment of GWI. We tested three botanicals (resveratrol [Polygonum cuspidatum], luteolin, and fisetin [Rhus succedanea]) on symptom severity of GWI in this placebo-controlled, pseudo-randomized clinical trial. Twenty-one male veterans with GWI completed the study protocol, which consisted of 1 month (30 days ± 3) of baseline symptom reports, 1 month of placebo, 1 month of lower-dose botanical, and 1 month of higher-dose botanical. Participants completed up to 3 different botanicals, repeating the placebo, lower-dose, and higher-dose cycle for each botanical assigned. Linear mixed models were used for analyses. Resveratrol reduced GWI symptom severity significantly more than placebo at both the lower (p = 0.035) and higher (p = 0.004) dosages. Luteolin did not decrease symptom severity more than placebo at either the lower (p = 0.718) or higher dosages (p = 0.492). Similarly, fisetin did not reduce symptom severity at either the lower (p = 0.504) or higher (p = 0.616) dosages. Preliminary findings from this screening study suggest that resveratrol may be beneficial in reducing symptoms of GWI and should be prioritized for future testing. Larger trials are required to determine efficacy, response rates, durability of effects, safety, and optimal dosage. This trial was registered on ClinicalTrials.gov (NCT02909686) on 13 September 2016.

This report is part of a larger study designed to rapidly and efficiently screen potential treatments for Gulf War Illness (GWI) by testing nine different botanicals. In this placebo-controlled, pseudo-randomized, crossover clinical trial of 20 men with GWI, we tested three botanical agents with putative peripheral and central anti-inflammatory actions: curcumin (Curcuma longa), boswellia (Boswellia serrata), and French maritime pine bark extract (Pinus pinaster). Participants completed 30 +/− 3 days of baseline symptom reports, followed by 30 +/− 3 days of placebo, 30 +/− 3 days of lower-dose botanical, and 30 +/− 3 days of higher-dose botanical. Participants then repeated the process with a new botanical until completing up to three botanical cycles. Data were analyzed using linear mixed models. Curcumin reduced GWI symptom severity significantly more than placebo at both the lower (p < 0.0001) and higher (p = 0.0003) dosages. Boswellia was not more effective than placebo at reducing GWI symptoms at either the lower (p = 0.726) or higher (p = 0.869) dosages. Maritime pine was not more effective than placebo at the lower dosage (p = 0.954) but was more effective than placebo at the higher dosage (p = 0.006). This study provides preliminary evidence that curcumin and maritime pine may help alleviate symptoms of GWI. As a screening study, a final determination of the efficacy of these compounds for all individuals with GWI cannot be made, and further studies will need to be conducted to determine strength and durability of effects, as well as optimal dosage. These results suggest that GWI may, at least in part, involve systemic inflammatory processes. This trial was registered on ClinicalTrials.gov (NCT02909686) on 13 September 2016.

Objective: The aim of the study is to investigate relationships between inflammatory analytes and symptoms of pain and fatigue in Gulf War illness (GWI). Methods: In this preliminary study, 12 male veterans meeting GWI criteria provided daily blood samples and symptom ratings over 25 days. Linear mixed models were used to analyze associations between symptoms and sera concentrations of cytokines, acute phase proteins, insulin, and brain-derived neurotropic factor. Results: Analyses included 277 days with both blood draws and self-reports. Days with worse fatigue severity were associated with higher C-reactive protein and serum amyloid A, and lower eotaxin 1. Muscle pain and joint pain were associated with leptin, monocyte chemoattractant protein 1, and interferon γ–induced protein. Joint pain was further associated with serum amyloid A and eotaxin 3. Conclusions: Gulf War illness involves fatigue and pain associated with inflammation. Conventional and novel anti-inflammatories should be further explored for the treatment of GWI.

Myalgic encephalomyelitis (ME/CFS) a chronic, disabling illness with no established etiopathology. It has been indicated in some population-based studies that Black and ethnic minority populations are underdiagnosed with ME/CFS. The aims of the present study were to (1) identify the agreement between receiving an ME/CFS diagnosis and meeting diagnostic criteria, (2) identify the demographic characteristics associated with receiving a diagnosis, and (3) explore patient satisfaction with healthcare. Self-reported medical history and symptoms were collected via online survey from respondents with and without fatigue. The agreement between self-reporting an ME/CFS diagnosis and meeting the Center for Disease Control’s (CDC) ME/CFS criteria or Institute of Medicine (IOM) criteria was assessed with Cohen’s kappa. Patient characteristics predicting a physician diagnosis were analyzed with logistic regression. Associations between diagnosis, demographics, and healthcare satisfaction were assessed with chi-square tests of independence. There were 1110 responses. The agreement between meeting ME/CFS criteria and reporting an ME/CFS diagnosis was fair (CDC: κ = 0.29; SE = 0.02; IOM: κ = 0.28, SE = 0.03). White respondents had 2.94 greater odds of being diagnosed with ME/CFS than non-White respondents. Having an ME/CFS diagnosis was associated with dissatisfaction with healthcare (χ² (3, N = 1063) = 14.17, p = 0.003). The findings suggest racial disparities in the diagnostic processes for ME/CFS.

Weather and air quality conditions have been anecdotally reported to be related to symptom fluctuations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), but this has never been empirically investigated. This exploratory study aims to examine the effects of weather and air quality on daily fluctuations of chronic pain and fatigue in women with ME/CFS. In an intensive longitudinal design, 58 participants with ME/CFS provided daily pain and fatigue ratings for an average of 61 days. Daily weather and air quality data were obtained from the National Oceanic and Atmospheric Administration and the US Environmental Protection Agency for the Birmingham, AL area. Linear mixed models revealed a significant relationship between days with more severe pain and worse Air Quality Indices (AQI, p < 0.001), lower wind speeds (p = 0.009), greater particulate matter (p = 0.037), and lower carbon monoxide (p = 0.004), sulfur dioxide (p = 0.003), and ozone levels (p = 0.015). Greater fatigue was associated with more particulates (p = 0.023) and lower barometric pressure (p = 0.048). These results suggest that air quality and weather can have small effects on ME/CFS symptom severity.