June 16, 2006

Family history of chronic pain not just ‘in their heads’

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Ok Yung Chung, M.D., and Stephen Bruehl, Ph.D., discuss data from their chronic pain studies.
Photo by Dana Johnson

Family history of chronic pain not just ‘in their heads’

Chronic pain seems to run in the family — if one or both parents have chronic pain, the child is more likely to suffer from it as well.

While this trend was previously explained by psychological factors, new research is pointing toward a biological — and perhaps genetic — basis.

In a recent study in the journal Pain, Stephen Bruehl, Ph.D., and Ok Yung Chung, M.D., report that people with a family history of chronic pain may have impairments in their body's natural pain-control system.

Several studies have demonstrated that such a history predicts an individual's risk of eventually developing chronic pain. Current estimates are that 14 percent of the U.S. population will suffer from chronic pain at some point in their lives.

“What intrigued me is … that positive family history seems to be associated with greater reports of spontaneous, acute pain as well,” said Bruehl, associate professor of Anesthesiology.

Previous attempts to explain these connections have focused on psychological factors like “modeling,” meaning that a person's reaction to pain is shaped by witnessing parents’ behavior, and hypervigilance, or being exceedingly aware of one's pain.

But Bruehl thinks there's more to it.

“If you have family history of chronic pain…affecting both chronic pain and acute pain, you have to look upstream — what would account for effects on both of these?”

Upstream means looking at the brain and the primary system in the brain that regulates pain responses, called the opioid system.

“There is a huge literature showing that endogenous opioids, which most people refer to as endorphins, are involved in pain regulation,” Bruehl explained.

Based on this, Bruehl and Chung suspected that individuals with a parental history of chronic pain would not be able to produce normal endogenous opioid pain relief when exposed to a stimulus that produces acute pain.

To test this, the researchers administered two different types of pain tests in two separate sessions. In one session, the subjects received saline (placebo) before the pain tests. In the other session, they received naloxone, a drug that blocks opioid receptors and thus impairs the body's natural pain-relief.

There were two main groups of subjects — those with a positive family history and those with no family history. Within those groups, the researchers also determined whether the subjects themselves were experiencing chronic lower back pain.

“If somebody has well-functioning opioid systems, when they get saline placebo, they won't respond much to the pain. But if you give the drug that blocks the endogenous opioids, they are going to hurt more,” Bruehl said.

As predicted, individuals with no parental history of chronic pain showed a significant increase in their pain levels when given naloxone. Those with a positive parental history were more sensitive to pain when given placebo and had no change in their level of pain when given naloxone, suggesting an impairment of their natural pain-control systems.

The researchers also found a significant interaction between family history and current low back pain.

“The people with the most severe impairments in their endogenous opioid system are those who have current chronic pain in combination with a positive parental history of chronic pain,” he said.

Bruehl suspects that this impairment of the endogenous opioid system could be a risk factor for developing chronic pain in the future. In addition, the results from this study show that family history's effects are not a purely psychological phenomenon.

Bruehl and colleagues have several ongoing studies to continue to probe the biological and genetic basis of natural pain control systems. A current study is examining the role of another brain chemical, norepinephrine, in chronic pain.

“The ultimate goal of the work we're doing is to improve treatment,” Bruehl said. “I don't think that it's an ideal solution to give patients long-term opiates because the side effects are very dramatic and (opiate) addiction is also a common problem.”

Although certain genes may be identified by this line of research, it's unlikely that scientists will ever find a “pain” gene like those that seem to predict a person's susceptibility to breast cancer, Bruehl said.

“But I do think it will help us to understand why some people may be at elevated risk of developing chronic pain. And for those individuals, it may be possible to identify treatments that enhance their natural pain control.

“What we've got for treating chronic pain right now is not ideal, and if we better understand what's contributing to chronic pain, maybe we can find a means for addressing these deficits with fewer side effects.”

The research was supported by grants from the National Institutes of Health.