Oxytocin and Arginine Vasopressin in Pain Relief

Objective:

It is well known that social and contextual cues and the whole atmosphere around the patient, such as words, attitudes, and providers behaviors, all contribute to evoke placebo responses. Moreover, an extensive literature investigating prosocial behaviors (e.g. ability to share another s feelings, imitation, mimicry) suggests that social modeling is critical in developing learning processes across species, including social influences on psychophysical aspects of pain. Only recently, it has been demonstrated that observing the beneficial effects in a demonstrator induces substantial placebo analgesic responses which are positively correlated with empathy. A crucial role in social behaviors is played by oxytocin (OXT) and arginine vasopressin (AVP), two neuropeptides, produced mostly in the hypothalamus and acting on certain brain regions whose function is associated with emotion perception (amygdale and nucleus accumbens), eye-gaze, trust and processing of positive and negative social cues. Since beliefs, trust and contextual cues are important elements of the clinicianpatient relationship and socially-induced placebo effects, it is reasonable to hypothesize that OXT and AVP may be one of the endogenous substances that trigger contextual and interpersonal placebo responses. By viewing interpersonal healing as a central causal process (or a set of related causal processes) within the domain of pain modulation, it is possible to probe the potential role for OXT and AVP in the modulation of a placebo response. In pursuit of this goal, we use a neuropharmacological intervention with OXT and AVP agonists in combination with a behavioral, brain imaging and genetic approach.

Study population:

Healthy men and women participants aging from 18 to 55 years.

Design:

We will investigate the role of oxytocinergic system in the processing of social cues by using a model of pain and interpersonal placebo analgesia already tested (9). The following drugs will be used: 1) oxytocin, 2) arginine vasopressin, and 3) placebo.

Outcome measures:

Primary outcomes are subjective pain reports (Experiment 1) and brain- and cortical -related responses (Experiments 2 and 3). Secondary measures include skin conductance response, heart rate, cortisol, subjective measures of empathy; trait and state anxiety measures; and functional pain-related genetic polymorphisms.