Brain vs. Pain

Medicine long has been puzzled by the “placebo effect,” named for the inert substances commonly administered to control groups in clinical trials of pharmaceuticals. Those given placebos often report an improvement in the symptoms they believe these “drugs” are intended to treat, despite the lack of any active ingredient in the placebo. Something is definitely happening, but just what is unknown. The subjects may simply be saying what they think the investigators want to hear. Their minds may be making them think they are improving with no actual change in condition. Or their beliefs really could be causing physiological changes, affecting the body through some mechanism involving the brain.

When it comes to pain, at least, UTMB psychiatry professor Robert Rose and colleagues elsewhere now have evidence suggesting that the third answer is right. Rose, executive director of the John D. and Catherine T. MacArthur Foundation Mind, Brain, Body, and Health Initiative, is among a number of investigators who published a report in the February 20, 2004, issue of Science describing the first use of magnetic resonance imaging to measure the pain-reducing effects of a placebo treatment.

The group, which also included scientists from Princeton, Harvard, the University of Michigan and the University of Wisconsin, exposed volunteer subjects to pain from electrical shock and heat in two separate studies. In both sets of experiments, the subjects reported feeling less pain when receiving a standardized painful stimulus on skin that had been treated with cream they were told would reduce pain than they felt on skin treated with what they were told was an inert “control” cream. In reality, the creams were identical: neither had any pain-reducing ingredients.

Functional magnetic resonance scans correlated with the subjects’ reports: the scans showed lower activity in pain-sensitive areas of the subjects’ brains (as measured by blood flow) when they received heat or electrical shock on skin treated with the supposed pain-reducing cream than on skin treated with the so-called control. Scans also showed that the placebo effect was tied to increased activity in the prefrontal cortex of the brain, an area associated with anticipation and planning. That led the researchers to conclude that expecting pain relief activates brain mechanisms responsible for the placebo effect.

Those results, Rose says, could have implications that go beyond pain to a whole range of bodily systems influenced by the brain, and beyond the “placebo pill” to include everything a caregiver does to create and maintain a patient’s belief that he or she will get better. “This larger concept of the placebo moves past the inert pharmacological pill to the psychology and changes in the patient’s expectancy, belief and hope that are engendered by the doctor,” Rose says. “We think there’s a real science behind doctors engendering belief and expectancy in patients. The brain is a big regulator of the autonomic nervous system, the hormones, and the immune system, which have a major physiological impact.”—Jim Kelly