Abnormal immune system response in the brain of women with Fibromyalgia after experimental endotoxin challenge.

Background: The pathophysiology of fibromyalgia (FM) is thought to include an overactive immune system, leading to central nervous system sensitization, allodynia, and hyperalgesia. We aimed to test this theory using an experimental immune system activation procedure and neuroimaging with magnetic resonance spectroscopic imaging (MRSI). Methods: Twelve women with FM and 13 healthy women (healthy controls; HC) received 0.3 or 0.4 ng/kg endotoxin and underwent MRSI before and after the infusion. Changes in brain levels of choline (CHO), myo-inositol (MI), N-Acetylaspartate (NAA), and MRSI-derived brain temperature were compared between groups and dosage levels using mixed analyses of variance. Results: Significant group-by-time interactions in brain temperature were found in the right thalamus. Post-hoc testing revealed that brain temperature increased by 0.55 °C in the right thalamus in FM (t(10) = -3.483, p = 0.006), but not in HCs (p > 0.05). Dose-by-time interactions revealed brain temperature increases in the right insula after 0.4 ng/kg (t(12) = -4.074, p = 0.002), but not after 0.3 ng/kg (p > 0.05). Dose-by-time interactions revealed decreased CHO in the right Rolandic operculum after 0.4 ng/kg endotoxin (t(13) = 3.242, p = 0.006) but not 0.3 ng/kg. In the left paracentral lobule, CHO decreased after 0.3 ng/kg (t(9) = 2.574, p = 0.030) but not 0.4 ng/kg. Dose-by-time interactions affected MI in several brain regions. MI increased after 0.3 ng/kg in the right Rolandic operculum (t(10) = -2.374, p = 0.039), left supplementary motor area (t(9) = -2.303, p = 0.047), and left occipital lobe (t(10) = -3.757, p = 0.004), with no changes after 0.4 ng/kg (p > 0.05). Group-by time interactions revealed decreased NAA in the left Rolandic operculum in FM (t(13) = 2.664, p = 0.019), but not in HCs (p > 0.05). A dose-by-time interaction showed decreased NAA in the left paracentral lobule after 0.3 ng/kg (t(9) = 3.071, p = 0.013) but not after 0.4 ng/kg (p > 0.05). In the combined sample, there was a main effect of time whereby NAA decreased in the left anterior cingulate (F[1,21] = 4.458, p = 0.047) and right parietal lobe (F[1,21] = 5.457, p = 0.029). Conclusion: We found temperature increases and NAA decreases in FM that were not seen in HCs, suggesting that FM patients may have abnormal immune responses in the brain. The 0.3 and 0.4 ng/kg had differential effects on brain temperature and metabolites, with neither dose effecting a stronger response overall. There is insufficient evidence provided by the study to determine whether FM involves abnormal central responses to low-level immune challenges.

A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Curcumin (Curcuma longa), Boswellia (Boswellia serrata), and French Maritime Pine Bark (Pinus pinaster).

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.

Effects of cannabinoid administration for pain: A meta-analysis and meta-regression.

Chronic pain states have resulted in an overreliance on opioid pain relievers, which can carry significant risks when used long term. As such, alternative pain treatments are increasingly desired. Although emerging research suggests that cannabinoids have therapeutic potential regarding pain, results from studies across pain populations have been inconsistent. To provide meta-analytic clarification regarding cannabis's impact on subjective pain, we identified studies that assessed drug-induced pain modulations under cannabinoid and corresponding placebo conditions. A literature search yielded 25 peer-reviewed records that underwent data extraction. Baseline and end-point data were used to compute standardized effect size estimates (Cohen's d) across cannabinoid administrations (k = 39) and placebo administrations (k = 26). Standardized effects were inverse-variance weighted and pooled across studies for meta-analytic comparison. Results revealed that cannabinoid administration produced a medium-to-large effect across included studies, Cohen's d = -0.58, 95% confidence interval (CI) [-0.74, -0.43], while placebo administration produced a small-to-medium effect, Cohen's d = -0.39, 95% CI [-0.52, -0.26]. Meta-regression revealed that cannabinoids, ß = -0.43, 95% CI [-0.62, -0.24], p < .05, synthetic cannabinoids, ß = -0.39, 95% CI [-0.65, -0.14], p < .05, and sample size, ß = 0.01, 95% CI [0.00, 0.01], p < .05, were associated with marked pain reduction. These outcomes suggest that cannabinoid-based pharmacotherapies may serve as effective replacement/adjunctive options regarding pain, however, additional research is warranted. Additionally, given demonstrated neurocognitive side effects associated with some constituent cannabinoids (i.e., THC), subsequent work may consider developing novel therapeutic agents that capitalize on cannabis's analgesic properties without producing adverse effects. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Hypnotizability and somatic complaints: a gender-specific phenomenon.

The relationship between hypnotizability and somatic illness was measured in 45 college students. Several weeks after completing the Waterloo-Stanford Group C Scale (WSGC), participants filled out a somatic-complaint checklist and measures of psychopathology. Results indicated a positive correlation between hypnotizability and somatic illness, and the relationship was stronger for female participants. In contrast to the quadratic model proposed by Wickramasekera, the current data demonstrated a linear relationship between hypnotizability and somatic complaint. Further analyses showed that somatic complaints were associated with hallucination and imagery items, corresponding to the perceptual-cognitive factor identified in Woody, Barnier, and McConkey's (2005) factor analysis of the Stanford Hypnotic Susceptibility Scale, Form C. The results call into question some claims that high hypnotizability is an adaptive and healthy trait.

Anatomy of a hypnotic response: Self-report estimates, actual behavior, and physiological response to the hypnotic suggestion for arm rigidity.

The present study closely examines subject response to the arm-rigidity item of the HGSHS:A. Subject behavior, subject self-report, and surface EMG of the biceps and triceps muscles were monitored. Two distinct ways of passing the item were observed and verified by EMG recordings: some subjects (tremblers) exerted muscular effort to bend the arm and kept it rigidly straight. Others (nontremblers) passively kept the arm straight without exerting muscular effort to bend, even though they reported exerting effort to bend their arm. These two behaviorally and physiologically different methods of passing the item support the idea of individual differences in hypnotic responding and suggest that subjects may be using different mental processes to pass the item.

The unique effects of forgiveness on health: an exploration of pathways.

The relationship of forgiveness, both state and trait, to health was assessed. Eighty-one community adults completed a packet of questionnaires and participated in a laboratory interview about a time of hurt or betrayal. Heart rate and blood pressure were recorded during a 10 min baseline, the interview and during a recovery period; interviews were structured around a framework of questions and videotaped. Four measures of forgiveness were all statistically associated with five measures of health (physical symptoms, medications used, sleep quality, fatigue, and somatic complaints). Trait forgiveness was associated with decreased reactivity (rate-pressure product) to the interview, but sympathetic reactivity did not account for the trait forgiveness-health association. Four mechanisms or pathways by which forgiveness could lead to fewer physical symptoms were examined: spirituality, social skills, reduction in negative affect, and reduction in stress. All factors either partially or fully mediated the effect of forgiveness on health; however, the strongest mediator for both state and trait forgiveness was reduction in negative affect. For state forgiveness, the second strongest mediator was reduction in stress; for trait forgiveness, both conflict management and reduction in stress were strong contributors.