May 11, 2000

Of Mice and Men and Women: The Genetics of Pain

Doctors have long observed that what appears to cause a lot of pain in one person may have little effect on another. Jeffrey Mogil thinks that the reason is in our genes.

Doctors and therapists have long recognized that people feel pain differently and that particular pain relievers help some people more than others.

According to Mogil, who is a professor of psychology and neuroscience at the University of Illinois, there are great differences from one individual to another in pain response, and corresponding differences in sensitivity to pain-relieving drugs. In other words, a mouse who is more sensitive to pain will get less pain relief from analgesics such as morphine, and a mouse who is less sensitive to pain will get more pain relief. The same phenomena have been observed in humans. Mogil's research suggests that the explanation is largely genetic.

In addition, there are physiogical differences between the sexes in how pain is experienced. "In addition to [the] apparent differences in magnitude," Mogil comments, "there appear to be fundamental neurochemical and genetic differences. Both [sexes] feel pain, but they are responding differently, by activating different circuitry in the brain."

Calling Mogil's research "very interesting," TheDoctor's expert Peter Barland, M.D., who's Professor of Medicine at New York's Albert Einstein College of Medicine as well as director of Rheumatology and director of the Immunodiagnostic Laboratory at Montefiore Hospital, points out that Mogil's findings on sex differences in pain perception may provide a clue to why fibromyalgia, a poorly-understood condition whose sufferers experience pain, fatigue and other symptoms, is much more common in women than in men.

"These differences," Barland adds, "may account for the different responses people have to the same analgesics; they suggest that future clinical trials of such drugs should be carefully sex- and age-matched, and be large enough to take into account genetic variations in pain response."

Doctors and therapists have long recognized that people feel pain differently and that particular pain relievers help some people more than others. "Arthritic people try over-the-counter remedies. Some work, some don't," Mogil says. "This implies that there are responders and non-responders. Wouldn't it be great if we could figure out why?"

One of Mogil's mouse experiments involved "tail-flick tests" in hot water. He found that 50 percent of animals tested both feel and respond to the pain, while 50 percent either feel it less or better tolerate it. Some of the differences can be explained by factors such as experience, age, stress and diet, but there are also sex differences and factors that reflect genotype, or inherited genes. Mogil believes that there is a mouse "pain gene." "Our technique tells us about where the pain gene is located, but it doesn't tell us what gene it is or exactly where it is located," he explains. The ongoing Mouse Genome Project (like its human counterpart, an attempt to sequence the entire genome of this species) may soon identify this gene.

According to Mogil, his research has three important implications for human medical treatment:
  1. Doctors should believe people when they say it hurts, recognizing that some people really do or do not feel pain given the same stimulus, and should be treated accordingly. "It seems this knowledge should lead to a de-stigmatization [of] people who are pain sensitive," he says. "There really are differences in our responses to pain."
  2. Soon, a pre-operation blood test may be developed which can determine a person's genetic response to pain, allowing for better treatment of post-surgical pain.
  3. It may someday be possible to reduce or eliminate chronic pain through gene therapy.
Reviewed by: Peter Barland, M.D.
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