Organ-specificity of placebo effects on blood pressure

Abstract

There is increasing evidence that verbal suggestions accompanying placebo interventions can alter autonomic functions. The underlying mechanisms of these changes are not well understood. However, previous studies point at the specificity of such effects. The aim of the experiment was to lower blood pressure by a placebo intervention and to investigate the specificity of autonomic changes. Forty-five healthy participants received a single administration of an active drug (a homeopathic remedy), an identically-looking placebo drug, or no drug. Active drugs and placebo drugs were administered in a double-blind design and were accompanied by verbal suggestions of a blood-pressure lowering effect. Systolic and diastolic blood pressure, the electrocardiogram, electrodermal activity, and the electrogastrogram were recorded during 30 min before and after the intervention, and changes in situational anxiety were assessed. Results indicated a decrease of systolic blood pressure in the placebo group, as compared to the control group. Diastolic blood pressure levels, heart rate, respiratory sinus arrhythmia, skin conductance, gastric slow-wave frequency and situational anxiety did not change differentially between groups. In conclusion, the reduction in systolic blood pressure following the placebo intervention could not be attributed to stress relief or anxiety reduction. Rather, results suggest that the placebo intervention specifically reduced systolic blood pressure.

Introduction

During the last decade, considerable progress has been made to understand the mechanisms of placebo effects in several neurological and psychiatric conditions, such as pain, Parkinson's disease, depression, and anxiety (Finniss et al., 2010). These studies pointed to the specificity of placebo effects. For example, many forms of placebo analgesia are associated with the release of endogeneous opioids, while placebo-induced motor improvement in patients with Parkinson's disease is related to the release of dopamine in the dorsal striatum (de la Fuente-Fernandez et al., 2004) and reduced activity of single neurons in the subthalamic nucleus (Benedetti et al., 2004). Furthermore, two studies found site-specific placebo effects on pain, that is, analgesia only in the placebo-treated part of the body (Montgomery and Kirsch, 1996, Benedetti et al., 1999). This specificity of placebo effects suggests that different placebo interventions may activate different networks in the brain, which set in motion discrete somatic and symptomatic responses.

Besides good evidence for placebo effects in several neurological and psychiatric diseases, there is increasing evidence that placebo interventions can also affect peripheral organ functions controlled by the autonomic nervous system (ANS). For example, verbal suggestions delivered during placebo interventions can change blood pressure, gastrointestinal motility, and lung function in comparison to adequate control conditions (Meissner, 2011). Only a few studies as yet have looked at the specificity of the effects. Butler and Steptoe (1986) addressed the specificity of a placebo intervention that prevented the bronchoconstriction of airways following a nocebo intervention (i.e., a placebo intervention accompanied by harmful suggestions, such as narrowing of the airways). Interestingly, the placebo intervention reversed the nocebo effect on the airways but not the concomitant effects on heart rate and skin conductance. The authors concluded that the placebo effect was organ specific in nature. In a recent study, Meissner (2009) showed that placebo interventions along with verbal suggestions of gastric stimulation or relaxation modulated the length of gastric contractions independently from changes in skin conductance, heart rate, and heart rate variability, likewise suggesting an organ-specific effect.

Regarding blood pressure, experiments in both healthy and hypertensive volunteers showed either a decrease or an increase of systolic blood pressure following verbal suggestions of a hypotensive or a hypertensive effect, respectively. Interestingly, diastolic blood pressure and heart rate were affected only by suggestions of blood pressure increase (Agras et al., 1982, Amigo et al., 1993, Hunyor et al., 1997). These findings suggest that blood pressure increases may be the result of a sympathetic stress response, while reductions in systolic blood pressure possibly reflect a target-specific effect. In order to further investigate the specificity of blood pressure reduction achieved by verbal suggestion, the present study aimed to decrease blood pressure by a placebo intervention and to investigate concomitant autonomic changes not only in the cardiovascular, but also in the electrodermal and gastrointestinal system.