Several studies have shown that male subjects report lower pain intensity to female compared to male experimenters. The present experiment examined whether experimenter gender also modulated autonomic pain responses. Sixty-four students (32 females) participated in a 2 Subject gender x 2 Experimenter gender x 15 Pain Tests mixed design. Six experimenters, three females and three males collected data. Heat pain was +48 degrees C induced to the right volar forearm. Subjective measurements consisted of pain intensity, pain unpleasantness, stress, arousal and mood. Autonomic responses were heart rate variability and skin conductance levels. The results revealed significant interactions between experimenter gender and subject gender on pain intensity and arousal, but there were no interactions in the physiological data. In conclusion, the lower pain report in male subjects to female experimenters is not mediated by changes in autonomic parameters, and the effect of experimenter gender is probably due to psychosocial factors.

Background: The purpose of this study was to assess the efficacy of transcranial direct current stimulation (tDCS) on verbal memory function in patients with Alzheimer’s disease. Methods: We conducted a randomized, placebo-controlled clinical trial in which tDCS was applied in six 30-minute sessions for 10 days. tDCS was delivered to the left temporal cortex with 2-mA intensity. A total of 25 patients with Alzheimer’s disease were enrolled in the study. All of the patients were diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association criteria. Twelve patients received active stimulation, and thirteen patients received placebo stimulation. The primary outcome measure was the change in two parallel versions of the California Verbal Learning Test–Second Edition, a standardized neuropsychological memory test normalized by age and gender. The secondary outcome measures were the Mini Mental State Examination, clock-drawing test, and Trail Making Test A and B. Results: Changes in the California Verbal Learning Test–Second Edition scores were not significantly different between the active and placebo stimulation groups for immediate recall (p = 0.270), delayed recall (p = 0.052), or recognition (p = 0.089). There were nonsignificant differences in score changes on the Mini Mental State Examination (p = 0.799), clock-drawing test (p = 0.378), and Trail Making Test A (p = 0.288) and B (p = 0.093). Adverse effects were not observed. Conclusions: Compared with placebo stimulation, active tDCS stimulation in this clinical trial did not significantly improve verbal memory function in Alzheimer’s disease. This study differs from previous studies in terms of the stimulation protocol, trial design, and application of standardized neuropsychological memory assessment. Trial registration: ClinicalTrials.gov identifier NCT02518412. Registered on 10 August 2015.

The hypothesis put forth is that expectations of treatment effects reduce negative emotions and thereby reduce symptoms, e.g. pain. Negative emotions increase pain, and it is hypothesized that placebos reduce pain by reducing negative emotions, i.e. feelings of nervousness, fear and anxiety. Placebo analgesia has been shown to be mediated via opioid activity, and relaxation increases opioid activity. The placebo acquires its relaxing effect due to verbal information that pain will be reduced, or due to associations between the placebo and the reduction in pain after effective treatment. Thus, the placebo signals that unpleasantness will be less after administration of the placebo. This involves negative reinforcement which is due to activation of a dopaminergic system that has been found to be activated during placebo analgesia and is involved in positive emotions. The nocebo effect of increased pain is, consistent with this model, because of increased fear and anxiety. The new aspect of the presented model is the hypothesis that expectations reduce negative emotions, and that negative reinforcement that involves the dopaminergic reinforcement system should be a contributor to placebo responses.

Previous studies suggest that transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) reduces chronic pain levels. In this randomized controlled trial, we investigated the effects of 5 consecutive 20-minute sessions of 2-mA anodal tDCS directed to the M1 in 48 patients (45 females) with fibromyalgia. Changes in pain, stress, daily functioning, psychiatric symptoms, and health-related quality of life were measured. Pain and stress were measured 30 days before treatment, at each treatment, and 30 days after treatment by using short message service on mobile phones. Patients were randomized to the active or sham tDCS group by receiving individual treatment codes associated either with the sham or active tDCS in the stimulator. Adverse effects were registered using a standardized form. A small but significant improvement in pain was observed under the active tDCS condition but not under the sham condition. Fibromyalgia-related daily functioning improved in the active tDCS group compared with the sham group. The stimulation was well tolerated by the patients, and no significant difference in the adverse effects between the groups was observed. The results suggest that tDCS has the potential to induce statistically significant pain relief in patients with fibromyalgia, with no serious adverse effects, but small effect sizes indicate that the results are unlikely to reflect clinically important changes.

Objectives: To examine whether there are gender differences in event-related potential (ERP) responses to painful stimulation after administration of placebo medication; and to investigate whether placebo medication reduces anticipatory stress and if this reduction can explain the placebo analgesic response. Several experimental and clinical studies have shown that males report lower pain compared with females. There are, however, few reports of gender differences in placebo analgesia. Methods: All subjects (n = 33; 17 women) participated in both a natural history and a placebo condition. ERPs were evoked by heat pulses with a peak at 52°C. Results: The results showed that pain unpleasantness and the N2/P2 ERP components were reduced in the placebo condition compared with the natural history condition. Only men displayed placebo responses in pain report and in the P2 component. Anticipatory stress was reduced after placebo administration, and the reduction in anticipatory stress was significantly related to the placebo effect on pain. Regression analyses revealed that the interaction of gender by anticipatory stress was significantly related to the mean placebo response, with men responding with lower stress after placebo medication, and larger placebo responses. Conclusions: A placebo response on pain unpleasantness was observed in men only, and reduced stress after placebo administration was observed in males only. Thus, reduced stress may be a mechanism for placebo responses in pain.