Pain Tolerance Determined by Single Amino Acid Replacement

Researchers into the genetic basis of pain tolerance found that a mutation in the gene that codes for the enzyme catechol-O-methyl transferase (COMT) determined how well healthy volunteers were able to tolerate levels of experimentally induced pain. Their findings were published in the February 21, 2003, issue of Science.

COMT, an enzyme linked to the metabolism of the neurotransmitter chemicals dopamine and noradrenaline, has two alleles that differ by one amino acid, either valine or methionine, at position 158. Investigators from the University of Michigan (Ann Arbor, USA) studied 29 participants, 15 men and 14 women, aged 20 to 30 years. The volunteers received injections of salt-water into their jaw muscles. The injections were meant to simulate temporomandibular joint pain disorder, which is a useful human model of sustained pain, and physical and emotional stress.

Positron-emission tomography (PET) brain-imaging scanning was used in combination with a radioactive tracer that illuminated mu-opioid receptors and indicated how the receptors become activated in the brain in response to a sustained pain stressor. The study showed that participants with two copies of the methionine form of the COMT gene had a much more pronounced response to pain than those who carried two copies of the valine form of the gene. Those with one copy of each form of COMT had a pain tolerance somewhere between the responses of the other two groups. At the molecular level, the valine form of the enzyme promoted a more effective dopamine-metabolizing system.

"Participants who had two copies of the valine form withstood quite a bit more pain than others in the study, while at the same time reporting that they felt less pain and fewer pain-related negative emotions,” explained first author Dr. Jon-Kar Zubieta, a neuroscientist at the University of Michigan. "This common genetic variation appears to influence individuals' pain response quite noticeably, both in their neurochemical response and in their affective responses and internal affective states. These data also emphasize the need to understand how genes influence our behavior by examining the intermediary brain pathways and mechanisms regulated by those genes.”




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