Intranasal oxytocin, sometimes called the "love hormone," intensified the painkilling effect of placebo in a clinical study, suggesting a physical basis for the placebo effect, researchers said.
Among 75 healthy young men exposed to painful heat stimuli on their forearms in the randomized, double-blind study, ratings of a placebo cream's analgesic effect were greater after the participants received active intranasal oxytocin than when they snorted a saline solution, with a difference of 5.76 points out of 60 (95% CI 0.59-10.93, P=0.03), according to Ulrike Bingel, MD, of the University of Duisberg-Essen in Germany, and colleagues.
"To our knowledge, our study provides the first experimental evidence that placebo responses can be pharmacologically enhanced by the application of intranasal oxytocin," they wrote in a research letter appearing in the Oct. 23/30 issue of the Journal of the American Medical Association.
The experiment was designed in such a way as to exclude the possibility that oxytocin itself affected pain sensitivity, the researchers said.
"We hypothesize that oxytocin might have increased the believability of the instructions by the study physician," Bingel and colleagues wrote. Also, they suggested, the hormone may have reduced anxiety and stress, which in turn could have increased the placebo response.
They had hypothesized that oxytocin might have such an effect because earlier research had associated its release with psychological traits such as trust, empathy, and socialization.
In the current study, participants were first randomized to receive either 40 IU of intranasal oxytocin or a saline solution. After 45 minutes, a cream was applied to each of their forearms. Participants were told that the cream on one arm was an anesthetic and that the other was an inert control product. They were also told that the anesthetic cream would take effect in 15 minutes.
During this period, heat was applied and increased until the participant rated the pain at 60 on a 100-point scale. The actual test phase then began, with 10 applications of heat at the 60-point intensity lasting for 20 seconds each, in 1-minute cycles. Participants rated the pain in each forearm for each of these applications.
At the "control" cream site, mean pain ratings averaged 59.96 in the oxytocin group and 58.31 in the saline group, effectively ruling out any real anesthetic effect of oxytocin.
Pain ratings for the "active" cream site averaged 47.11 in the oxytocin group versus 51.23 in the saline group. Bingel and colleagues then calculated the placebo response at each site by subtracting the "active" site rating from the "control" site rating. For the oxytocin group, this worked out to 12.84 points (95% CI 8.67-17.01); in the saline group, it was 7.08 points (95% CI 3.84-10.31).
There were no significant differences between the groups in other measures, such as the temperature needed to achieve the 60-point rating at baseline (46° C [115° F] in both groups) or in anxiety or depression levels.
After the experiment, participants were asked to guess whether they had received oxytocin or saline. Most of those guessing oxytocin had actually received saline, Bingel and colleagues indicated. Just over half of those who guessed saline were in the oxytocin group.
"Further studies are needed to replicate our findings in larger clinical populations, identify the underlying mechanisms, and explore moderating variables such as sex or aspects of patient-physician communication," the researchers concluded.