Per M. Aslaksen

The effect of experimenter gender on autonomic and subjective responses to pain stimuli.

Abstract 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 × 2 Experimenter gender × 15 Pain Tests mixed design. Six experimenters, three females and three males collected data. Heat pain was +48 °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.

The relation of emotions to placebo responses

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.

Gender Differences in Placebo Analgesia: Event-Related Potentials and Emotional Modulation

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. ERP = event-related potential; NRS = Numerical Rating Scale.

The roles of physiological and subjective stress in the effectiveness of a placebo on experimentally induced pain.

Objective: To examine whether reduction of negative emotions and associated autonomic activity could explain placebo analgesia, and to test the effect of experimenter gender on the placebo analgesic response. Methods: Sixty-three (n = 32 females) students participated in a within-subjects design where subjects were tested on two separate days, one day for the experimental condition (placebo) and one day for the natural history condition. In the experimental condition, the participants received capsules containing lactose with information that the capsules were a high dose of a potent painkiller. In the natural history condition, the procedures were identical except that the placebo capsules were not administrated. The experimenters were blinded to the fact that all participants received placebo. Pain was induced by a thermode holding +46°C with duration of 240 seconds to the forearm. Electrocardiogram was measured to obtain data for analysis of heart rate variability. Subjective measurements consisted of pain intensity, pain unpleasantness, stress, arousal, and mood. Results: The results showed a placebo effect on pain intensity and a concomitant reduction in subjective stress and cardiac activity. Stepwise regressions revealed that reduced subjective stress was the only predictor for the placebo analgesic response. Contrary to our hypothesis, male subjects displayed increased placebo analgesia when a male acted as experimenter. Conclusions: The results indicate that reduced negative emotional activation could be a mechanism in placebo analgesia and that experimenter gender is probably not systematically related to placebo analgesia. ECG = electrocardiogram; HRV = heart rate variability.

Variability in placebo analgesia and the role of fear of pain—an ERP study

Summary The relation of fear of pain to placebo analgesia was investigated. Fear of pain was associated with reduced placebo analgesia in subjective reports and event‐related potentials. Abstract Fear of pain (FOP) and its effect on placebo analgesia was investigated. It was hypothesized that FOP should interfere with placebo‐mediated pain inhibition and result in weaker placebo responding in pain intensity, pain unpleasantness, stress, and event‐related potentials to contact heat pain. Thirty‐three subjects participated in a balanced 2 condition (natural history, placebo) × 3 test (pretest, posttest 1, posttest 2) within‐subject design, tested on 2 separate days. FOP was measured by the Fear of Pain Questionnaire and subjective stress by the Short Adjective Check List. Placebo effects were found on reported pain unpleasantness and N2 and P2 amplitudes. FOP was related to reduced placebo responding in pain unpleasantness, but this was only evident for the subjects who received the placebo condition on day 1. Subjects who received the placebo condition on day 1 experienced more pretest stress than those who received the placebo condition on day 2 (ie, reversed condition order), and this explained the interaction effect on placebo responding. FOP was related to reduced placebo responding on P2 amplitude, whereas placebo responding on N2 amplitude was unaffected by FOP. Higher placebo responses on N2 and P2 amplitudes were both related to higher placebo analgesic magnitude in pain unpleasantness. In conclusion, increased FOP was found to reduce subjective and electrophysiological placebo analgesic responses.

Is fear of pain related to placebo analgesia

OBJECTIVE Verbal information that a painkiller has been administered generates an expectation of pain relief which in turn decreases pain. This expectation-based pain reduction is termed placebo analgesia. We hypothesized that fear of pain would be related to higher stress and pain intensity and to reduced placebo analgesia. METHODS Sixty-three students (30 females) participated in a Two-Condition (placebo, natural history)xFive-Test (one pretest, four post-tests) within-subjects design. Heat pain was induced by a 30x30-mm contact thermode to the medial volar forearm. Each pain test lasted for 4 min at a temperature of 46 degrees C. Stress, arousal, and pain intensity and pain unpleasantness were rated on 100-mm visual analogue scales. RESULTS Fear of pain was related to higher anticipatory stress and to higher stress and pain intensity during pain. Fear of pain was also related to reduced placebo analgesic responding. CONCLUSION Fear of pain was positively related to stress both during pain and in the anticipation of pain, and negatively related to placebo analgesia. Previous research has indicated a role for increased stress in the nocebo response, and the present findings suggest that decreased stress may strengthen the placebo response.

Prediction of on-road driving ability after traumatic brain injury and stroke

The aim of the study was to examine the predictive value of widely used standardized neuropsychological tests in a clinical setting for on‐road driving performance in patients with cerebral stroke or traumatic brain injury (TBI), and to provide cut‐off values for neuropsychological test results under which driving should not be recommended.

Transcranial direct current stimulation as a treatment for patients with fibromyalgia: a randomized controlled trial.

Abstract 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.

Opposite effects of the same drug: reversal of topical analgesia by nocebo information.

Abstract Several studies have shown that psychological factors such as learning, expectation, and emotions can affect pharmacological treatment and shape both favorable and adverse effects of drugs. This study investigated whether nocebo information provided during administration of an analgesic cream could reverse topical analgesia to hyperalgesia. Furthermore, we tested whether nocebo effects were mediated by negative emotional activation. A total of 142 healthy volunteers (73 women) were randomized into 6 groups. A topical analgesic cream (Emla) was administered together with suggestions of analgesia in 1 group, whereas another group received Emla with suggestions of hyperalgesia. Two other groups received a placebo cream together with the same information as the groups receiving Emla. A fifth group received Emla with no specific information about the effect, and the sixth group received no treatment but the same pain induction as the other groups. Heat pain stimulation (48°C) was administered during a pretest and 2 posttests. Pain was continuously recorded during stimulation, and measures of subjective stress and blood pressure were obtained before the pretest, after the application of cream, and after the posttests. The results revealed that pain was significantly lower in the group receiving Emla with positive information and highest in the groups receiving suggestions of hyperalgesia, regardless of whether Emla or the placebo was administered. Mediation analyses showed that stress and blood pressure mediated hyperalgesia after nocebo suggestions. These results suggest that nocebo information can reverse topical analgesia and that emotional factors can explain a significant proportion of variance in nocebo hyperalgesia.

Neuropsychological functioning in a national cohort of severe traumatic brain injury: demographic and acute injury-related predictors

Objectives:To determine the rates of cognitive impairment 1 year after severe traumatic brain injury (TBI) and to examine the influence of demographic, injury severity, rehabilitation, and subacute functional outcomes on cognitive outcomes 1 year after severe TBI. Setting:National multicenter cohort study over 2 years. Participants:Patients (N = 105), aged 16 years or older, with Glasgow Coma Scale score of 3 to 8 and Galveston Orientation and Amnesia Test score of more than 75. Main Measures: Neuropsychological tests representing cognitive domains of Executive Functions, Processing Speed, and Memory. Injury severity included Rotterdam computed tomography score, Glasgow Coma Scale score, and posttraumatic amnesia (PTA) duration, together with length of rehabilitation and Glasgow Outcome Scale–Extended score. Results:In total, 67% of patients with severe TBI had cognitive impairment. Executive Functions, Processing Speed, and Memory were impaired in 41%, 58%, and 57% of patients, respectively. Using multiple regression analysis, Processing Speed was significantly related to PTA duration, Glasgow Outcome Scale–Extended score, and length of inpatient rehabilitation (R2 = 0.30); Memory was significantly related to Glasgow Outcome Scale–Extended score (R2 = 0.15); and Executive Functions to PTA duration (R2 = 0.10). Rotterdam computed tomography and Glasgow Coma Scale scores were not associated with cognitive functioning at 1 year postinjury. Conclusion:Findings highlight cognitive consequences of severe TBI, with nearly two-thirds of patients showing cognitive impairments in at least 1 of 3 cognitive domains. Regarding injury severity predictors, only PTA duration was related to cognitive functioning.