Mind control: Keefe focuses on the brain's ability to control pain

Les Todd

When Edwards was an undergraduate at Winston-Salem State University, his mentor, psychologist Nelson Adams, handed out a stack of materials for his students to read. Overwhelmed by the sheer volume, Edwards skimmed the articles quickly—until one in particular caught his eye. Culled from the popular press, it discussed how hormones can influence memories, either by sharpening them or by making them blurrier. Scientists have long known that the body protects itself from physical discomfort by releasing hormones—think of how endorphins serve as natural painkillers. Intuitively, it makes sense for the body to have a similar mechanism for blunting psychological discomfort by helping us forget pain. By the time Edwards had entered college in the 1980s, researchers had conducted some animal studies on this question. But "there was not a lot of human work," he says.

Edwards became fascinated by the intersection of hormones, pain, and cognition. His interest persisted as he entered graduate school at the University of Kentucky. For his dissertation, Edwards subjected a group of female volunteers to a pain-making device that used weights to compress their fingers. Afterwards, half the women took a placebo; the others took the drug naltrexone, which blocks the effects of endorphins in the body. He then administered the California Verbal Learning Test, a standard instrument that measures memory.

The women who took naltrexone aced the tests; they had no changes in memory. But the ones who took the placebo—that is, whose bodies were allowed to react to endorphins normally—had a dramatic deterioration in how much they could recall. This suggested the endorphins reduce the amount of information trauma victims can store—perhaps to protect them from the distress of remembered pain. "If you're hit by a car," Edwards asks, "how productive is it to remember the first sound of crushing or the feeling of a rear wheel breaking an arm and a leg?" Likewise, he says, there's an evolutionary advantage for women to forget the agony of childbirth: It makes them more willing to endure another pregnancy and pass on their genes.

In 1996, Edwards came to Duke for a dual fellowship in psychiatry and endocrinology. There, he met Elaine Whitworth, director of education at Duke's Comprehensive Sickle Cell Center. At the time, Edwards knew little about sickle cell disease, a painful genetic disorder marked by misshapen red blood cells. Over time, he came to learn that the condition, which, in the United States, primarily strikes African Americans, was seriously understudied. "There was almost no research into psychosocial factors in sickle cell disease," he says. "Almost anything I contributed would be significant."

Administering lengthy questionnaires to Duke's sickle-cell patients, Edwards looked at three survival skills common among African Americans: prayer, hostility, and the single-minded determination known as "John Henryism." Only one of those strategies had an unambiguous impact, he found: Hostility significantly increased depression and anxiety, making it harder for patients to cope with pain.

The effect of John Henryism, a term often defined as "prolonged, high-effort coping with difficult psychological stressors," was somewhat more complex. Coined by Sherman James, a social epidemiologist at Duke's Terry Sanford Institute of Public Policy, the term derives from the tale of the mythical African-American railroad worker who defeats a steam-powered drill in a steel-driving contest and dies afterward. Edwards learned that the success or failure of patients who scored high on the John Henryism scale varied based on whether they also had money, strong family and community ties, and ready access to medical care. "With adequate resources, these patients shine," Edwards says. For patients lacking these resources, though, "John Henryism is a predictor of depression and anxiety." It can also be a predictor of physical pain: If a sickle-cell patient has a fierce determination to succeed but lacks the workplace support to take sick leave, he or she might try to work through an intensive period of pain. This, in turn, can lead to more pain.

Prayer also yielded complicated results. Pain patients who prayed several times a week and who attended church with some frequency tended to suffer less than others from depression and anxiety. "It absolutely surprised me," Edwards says. But, upon reflection, he realized that prayer serves a similar purpose to the calming techniques used by Keefe's research subjects. Edwards says health professionals should work with these findings: Rather than teaching some religious patients yoga or guided imagery, clinicians could encourage these patients to keep praying. "If you're getting deep relaxation from your prayer, and getting medical benefit, why would you teach the patient another skill?" he asks.

But this benefit disappeared with the most religious patients, the ones who prayed at least once a day and attended church with the most frequency. They actually suffered the highest levels of depression, anxiety, and psychosomatic symptoms, along with kinesiophobia, the fear of movement and reinjury. "In essence, prayer appears to be a very effective pain-coping skill until it is used exclusively and to the exclusion of other active coping strategies," Edwards says. "There is a time for prayer and there is a time for action."

In his clinical practice, Edwards has found that some very religious patients are resistant to taking their medications. "Many patients view their pain as coming from God and are less likely to want to do something about their pain," Edwards says. "They think it's punishment for something they did earlier in their lives." Faced with such noncompliance, "we often can match a patient with a clinician of a similar orientation. If a patient believes this is from God, we assist them in broadening their thinking: Possibly God is empowering you to overcome this obstacle."

Psychosocial interventions like these are a long way from simply prescribing painkillers. But, Edwards says, "narcotics only attend to biology," while a patient's pain is often a mélange of physical, psychological, and social factors. "It's not a single piece of tissue" involved in an injury, he says. "The treatment needs to be equally comprehensive."