Intrinsic remedies for pain: placebo effect may take various paths in brain.

The brain draws on a range of pain-fighting options when people receive sham treatments for pain, a new brain-imaging study suggests.

People who experienced pain relief after receiving fake acupuncture treatments displayed pronounced activity in certain brain areas, says a team led by neuroscientist Jian Kong of Massachusetts General Hospital in Charlestown. This pattern of brain activity differed from that reported in 2004 by another team, directed by neuroscientist Tor D. Wager of Columbia University.

In that work, a placebo cream applied to the skin diminished pain. In both experiments, the researchers induced volunteers' pain by applying heat to the forearm.

"There may be multiple brain mechanisms underlying placebo [pain relief]," Kong says. He and his colleagues describe their findings in the Jan. 11 Journal of Neuroscience.

Kong's group established the pain tolerance of 16 volunteers, ages 22 to 35. Using a device that delivered heat to the right forearm, the scientists noted how much heat was needed to yield ratings of low or high pain.

Volunteers then read information about acupuncture before receiving on their right arms a sham acupuncture treatment that they had been told was real. The placebo acupuncture needle retracted into its casing when pressed against the skin. To encourage expectations of the sham acupuncture's effectiveness, without telling the volunteers, the researchers slightly decreased the temperature of ensuing heat pulses delivered to participants' right arms.

Next, a functional magnetic resonance imaging scanner measured blood flow throughout volunteers' brains as low- and high-pain heat pulses were delivered to their right or left arms.

A placebo effect emerged. Individuals reported feeling substantially less pain in their right arms than in their left arms during delivery of equally intense heat. Placebo responses were accompanied by pronounced blood flow, a sign of intense neural activity, in six brain regions, the scientists say. These areas regulate pain perception, monitoring of external events, and negative emotions such as anxiety.

In contrast, Wager's team linked placebo responses to diminished activity in pain-sensitive regions overlapping those identified in Kong's study.

Wager points out that Kong's team measured elevated activity in pain-related brain regions shortly after volunteers started to feel pain, whereas his team looked at a later phase of pain. Neural activity in affected regions diminishes as pain continues, his study indicated.

However the brain orchestrates such effects, positive expectations can even reduce pain controlled by spinal cord signals, say neuroscientist Dagfinn Matre of the National Institute of Occupational Health in Oslo and his colleagues.

Earlier research had shown that nerve projections from the spinal cord create temporary, extreme pain sensitivity in heated-skin areas. To produce that effect, the scientists delivered heat pulses to the right forearms of 29 volunteers for 5 minutes.

The right forearms of 19 of the volunteers were then heated by an instrument containing a sham magnet that they had been told was a pain-relieving device. Those participants reported a smaller area of pain and less pain overall than those who didn't expect pain relief, the researchers report in the same issue of the Journal of Neuroscience.