Study Finds Brain's Reward Areas Also Activated By Pain; Imaging Study May Lead To Improved Diagnostic, Treatment Methods

December 2001

The experiences of pain and pleasure have been described as the extreme ends of a continuum. Now a study from Massachusetts General Hospital (MGH) supports that concept by finding that brain structures previously shown to react to rewarding experiences are also activated, although in distinctive ways, by pain. The result, which appears in the December 6 issue of Neuron, may lead to a better understanding of the effects of pain within the brain and eventually to new ways to diagnose and treat pain.

"Pain is a complex experience that includes both a sensation and an emotional reaction," says David Borsook, MD, PhD, director of the MGH Center for Functional Pain Neuroimaging and Therapy Research, Department of Radiology, the paper?s senior author. "Understanding this emotional component would be key to developing new approaches to helping chronic pain patients, who are at increased risk for anxiety, depression and suicide."

To track brain activity in response to pain, the researchers took functional MRI (fMRI) images of the brains of eight study volunteers. The volunteers, all healthy young men, had a thermode (small heat pad) attached to their hands, which administered warm or hot temperatures for brief periods, alternating with normal skin temperatures. Brain images focused both on areas previously identified as involved with the sensory experience of pain and on areas identified in earlier studies as being activated in response to such stimuli as cocaine, food and money.

The results showed that the painful 'hot' temperatures caused activation not only of the classic pain circuitry but also of some of the areas previously described as a reward circuitry. In some of these reward-associated structures, particularly in an area called the nucleus accumbens, the pattern of activity produced by the painful stimuli was opposite to that seen in studies of rewarding stimuli. In addition, activity in these so-called reward structures changed over time; they were most active immediately after heat administration began and then returned toward baseline. In contrast, those structures associated with the sensation of pain were most active later in the brief (25-second) heat administration period.

"We were quite surprised to see these early and late responses, with the reward structures responding earlier than the pain circuits," says Lino Becerra, PhD, the study?s first author. "These are two brain systems that were never associated in the past, and it?s the first time that we have seen something aversive activating these reward structures."

Co-author Hans Breiter, MD, of the Motivation and Emotion Neuroscience Center in the MGH Department of Radiology, adds, "This study supports the concept that there is a continuum between reward and aversion. It would appear that the philosophers Spinoza and Bentham, who proposed that pleasure and pain were part of the same spectrum, were right."

"It may be that these circuits previously described as handling reward are actually analyzing stimuli and judging which are important to survival," Borsook says. "I?m hopeful that these results will help us understand how chronic pain produces changes in the brains of patients. For example, many chronic pain patients report that they cannot enjoy any pleasurable experience ? even something as simple as going to a movie. This interaction of brain systems also may explain why patients can take opioid drugs for pain without becoming addicted."

Among possible applications of these results cited by the researchers are developing objective tests to measure pain and pain relief and the creation of pain-relieving drugs that target the structures previously associated with reward, a strategy which may treat types of pain that do not respond to traditional medications, which target the pain perception system.

Other co-authors of the study are Gilberto Gonzalez, MD, MGH director of Neuroradiology, and Roy Wise, PhD, of the National Institute on Drug Abuse (NIDA). The work was supported by grants from the Mayday Fund, NIDA, the Office of National Drug Control Policy and Counterdrug Technology Assessment Center, and from the Kaneb, Goldfarb and Slifka families.

The Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $300 million and major research centers in AIDS, the neurosciences, cardiovascular research, cancer, cutaneous biology, transplantation biology and photomedicine. In 1994, the MGH joined with Brigham and Women?s Hospital to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups and nonacute and home health services.

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