A team led by Dr. Simon Kessner of the University Medical Center Hamburg-Eppendorf, Germany, investigated the impact of oxytocin on the intensity of perceived pain.
They gave 80 healthy male volunteers, aged 20 to 38 years, either 40 IU (International Units) of oxytocin or saline, at random, without telling the participants which they were receiving. Both were delivered by a nasal spray.
After 45 minutes, the participants all had two ointments applied to their forearm. The ointments were inert and identical, but one was described as an anesthetic that reduces pain, and the other was described as inert. After 15 minutes (for the “anesthetic” to work) a 20-second painful heat stimulus was applied to a different area of the arm.
Pain was then rated on a scale from zero (no pain) to 100 (unbearable pain). For each individual, the temperature that led to a pain rating of 60 was recorded. Next, heat of this temperature was applied ten times to each of the two ointment sites in randomized order, and the pain was rated again each time.
Although the applied heat was identical on both sites, pain was rated as relatively lower at the placebo (fake anesthetic) site among those given oxytocin. This indicates a reduction in perceived pain intensity at the placebo site versus the control site in the oxytocin group.
Oxytocin itself had no analgesic effect, as shown by very similar pain scores at the “control” site, where the participants were told an inert cream had been applied.
Details appear in the Journal of the American Medical Association. The authors report that oxytocin had no side effects.
They said, “Placebo responses have been shown to contribute to clinical treatment outcomes. The pharmacological enhancement of placebo responses therefore has the potential to increase treatment benefits.
“To our knowledge, our study provides the first experimental evidence that placebo responses can be pharmacologically enhanced by the application of intranasal oxytocin. Further studies are needed to replicate our findings in larger clinical populations, identify the underlying mechanisms, and explore moderating variables such as gender or aspects of patient-physician communication.”
They suggest that oxytocin, involved in childbirth and breastfeeding, may also play a role in empathy, trust, and social learning, which are all vital for the patient-physician relationship, itself an “important mediator of placebo responses.”
A Second Study
A separate study investigated brain activity when the placebo effect is underway, using patients with irritable bowel syndrome. The researchers, from the University of Florida, carried out fMRI brain scans during tests involving 20 seconds of rectal distension.
One group was given a local anesthetic and the other a “verbally induced placebo,” i.e. they were told an anesthetic had been used. The real anesthetic reduced pain and pain-related brain activity, as predicted. But “verbal suggestion of a placebo” also reduced perceived pain and increased brain activity in “areas that process placebo suggestions,” said the team.
“These placebo suggestions led to significant decreases in activity of brain areas that process pain,” the team reports. They add that this concurs with the idea that placebo analgesia is linked to “somatic focus and sensory feedback.”
“Expectations for pain can be verbally manipulated to produce placebo analgesia,” they write in the Journal of Pain. Verbal suggestions “may enhance placebo analgesia by engaging a feedback mechanism triggered by the painful stimulus itself and related to brain mechanisms involved in memory and semantic processing,” they conclude.
A 2013 review of the placebo effect explains that placebo responses are “complex psychoneurobiological events” which involve the central nervous system and other physiological mechanisms to influence pain perception, clinical symptoms, and the response to drugs.
Many research studies over recent years have advanced our knowledge of the neuropsychological, genetic, and brain-related elements of the placebo effect, and how individuals may differ in their response.
It is already known that the analgesic strength of the placebo effect is influenced by many factors including past exposure to effective analgesic agents and persuasive suggestions of a painkilling effect.
Strategies to maximize the placebo analgesic effect could be extremely helpful in clinical practice, and may well benefit from the inclusion of oxytocin as well as knowledge of the best verbal strategies to use.
Kessner, S., Sprenger, C., Wrobel, N., Wiech, K., Bingel, U. Effect of Oxytocin on Placebo Analgesia: A Randomized Study. JAMA, 23 October 2013 doi:10.l001/jama.2013.277446
Craggs, J. G., Price, D.D., Robinson, M.E. Enhancing the placebo response: fMRI Evidence of Memory and Semantic Processing in Placebo Analgesia. The Journal of Pain, 9 January 2014 doi: 10.1016/j.jpain.2013.12.009
Colloca, L., Klinger R., Flor, H., Bingel, U. Placebo analgesia: psychological and neurobiological mechanisms. Pain, April 2013 doi: 10.1016/j.pain.2013.02.002