1) Two studies showed that observing another person experience more pain (a "nocebo response") can lead to hyperalgesia, or increased sensitivity to pain, through social learning and observational conditioning. 2) The magnitude of hyperalgesia was correlated with traits like empathy and catastrophizing. Observing male models led to greater hyperalgesia than female models. 3) These findings have implications for clinical trials and medical practice, as observing unsuccessful treatments or others' pain responses can negatively influence patients through social learning and nocebo effects.

1. CopiaautorizadaporCDR
Commentary
Responding to nocebos through observation: Social contagion of negative emotions
Humans and animals can learn in a number of ways, including
observation and imitation. Pain is powerfully influenced by social
interactions [1], so its modulation by observation can be as
effective as for other perceptions and behaviors. For example, in
a previous study on placebo analgesia [2], subjects underwent a
placebo treatment after they had observed a demonstrator show-
ing analgesic effects when the painful stimuli were paired with a
green light. The observation of these beneficial effects was enough
to induce substantial placebo analgesic responses that were posi-
tively correlated with empathy scores. This social observational
learning produced placebo responses that were similar to those in-
duced by directly experiencing the benefit through a conditioning
procedure, thus showing that placebo analgesia is powerfully and
finely tuned by observation.
In this issue of PAINÒ
, 2 studies independently show that the
same social effects can be obtained in the opposite direction,
namely, nocebo hyperalgesia [3,4]. In both studies, the experimen-
tal subjects observed a model who simulated more pain in associ-
ation with either a red light in the study [3] or the application of an
ointment on the skin in the study [4]. After the observation phase,
the experimental subjects showed robust nocebo responses, ie,
hyperalgesic responses following the presentation of the red light,
and this was correlated with empathy scores [3]. Likewise, sub-
stantial nocebo responses were found after the observation of the
ointment application, and this was correlated with pain catastro-
phizing [4]. In addition, the study [3] found a gender effect, where-
by nocebo hyperalgesia was greater after a male model was
observed compared to a female model, regardless of the sex of
the experimental subjects.
These 2 studies are important for at least 3 reasons. First, they
show that social learning can modulate not only placebo analgesia,
but nocebo hyperalgesia as well, which underscores the impor-
tance of observation and social interaction in the overall placebo/
nocebo phenomenon. Second, in addition to a social effect, a
gender effect may be important as well, and this is related to the
sex of the model: males simulating pain are apparently more
effective than females. Third, a correlation was found between
the magnitude of the nocebo hyperalgesic responses and some
personality traits (empathy and catastrophizing), as already found
in placebo analgesic responses [2].
These findings may have profound implications in both the clin-
ical trial setting and in medical practice. In the first case, observa-
tion of others must be taken into consideration whenever a clinical
trial is performed. Patients participating in a clinical trial may be
dramatically influenced by observing other patients belonging to
the same trial. For example, communication among patients
enrolled in the same clinical trial is common, and this may influ-
ence either positively or negatively the therapeutic outcome. In
the second case, doctors and psychologists must consider the pos-
sible negative impact that the observation of unsuccessful treat-
ments may have on their patients. This holds true not only in
routine medical practice but in daily life as well, whenever others’
suffering and negative outcomes are observed, eg, through the
media.
Different aspects of our society can be involved in these
phenomena, from magic rituals, whereby negative expectations
can be induced (eg, voodoo), to modern medicine, whereby the
origins of many side effects can be psychological (eg, following
negative diagnoses or anticipating chemotherapy effects), and to
exaggerated health warnings by the media (eg. side effects
supposed to be elicited by cell phones). In all these instances, social
observational learning can lead to a negative emotional contagion
across individuals, with the consequent activation of nocebo mech-
anisms. It is interesting that in a recent study [5], experimental
subjects observed judgments that some people made about a pain-
ful stimulus before they received the same stimulus themselves.
Uncertainty about the intensity of the pain stimulus led to a
specific and powerful hyperalgesic effect, and this was correlated
by activity in the periaqueductal gray. All these studies highlight
the role of social interaction in the global experience of pain and
represent the basis for future research and insights into the
mechanisms of socially modulated pain, including the possible
applications in pain management.
References
[1] Singer T, Seymour B, O’Doherty J, Kaube H, Dolan RJ, Frith CD. Empathy for pain
involves the affective but not sensory components of pain. Science
2004;303:1157–62.
[2] Colloca L, Benedetti F. Placebo analgesia induced by social observational,
learning. PAINÒ
2009;144:28–34.
[3] S´wider K, Ba˛bel P. The effect of the sex of a model on nocebo hyperalgesia
induced by social observational learning. PAINÒ
2013;154:1312–7.
[4] Vögtle E, Barke A, Kröner-Herwig B. Nocebo hyperalgesia induced by social
observational learning. PAINÒ
2013;154:1427–33.
[5] Yoshida W, Seymour B, Koltzenburg M, Dolan RJ. Uncertainty increases pain:
evidence for a novel mechanism of pain modulation involving the
periaqueductal gray. J Neurosci 2013;33:5638–46.
Fabrizio Benedetti
Department of Neuroscience,
University of Turin Medical School and
National Institute of Neuroscience, Turin, Italy
Tel.: +39 011 670 8492.
E-mail address: fabrizio.benedetti@unito.it
0304-3959/$36.00 Ó 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.pain.2013.05.012
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