Tiny gene changes means big differences in pain

18:16 21 February 03
NewScientist.com news service

When it comes to pain, a tiny variation in a single gene divides the men from the boys, reveals a new study.

US researchers have pinpointed differences in the way people withstand pain - both physical and emotional stress - to a gene which makes a protein important for brain chemistry.

The gene makes catechol-O-methyl transferase (COMT), an enzyme vital for mopping up the dopamine brain chemical linked with sensing pain.

Tough guys and wimps carry different forms of the gene, showed Jon-Kar Zubieta and his team at the University of Michigan and The National Institute of Alcohol and Alcoholism, Rocksville, Maryland.

People with a particularly active form of COMT were hardier, whereas people with a lazier form felt pain more acutely. Those with both forms of the gene, one from each parent, experienced intermediate pain, the researchers found.

Zubieta, told New Scientist: "This is the first time that a gene has been linked to particular changes both to the chemical systems of the brain and behaviour."


Lazier genes

The COMT gene exists in two forms which make copies differing by a single amino acid only - either valine or methionine.

This small variation has a big effect on the activity of COMT, say the researchers. People with the laziest form of the gene - who have two copies of the methionine version - make enzymes three- to four-fold less effective than the other variants contained just valine or one of each.

The team used brain imaging or positron emission tomography to examine the brain activity of 29 people who were subjected to a "tolerable" pain over 20 minutes.

The volunteers were given a salt water injection into their jaw muscles to simulate a condition called temporomandibular joint pain disorder. They rated their own level of pain every 15 seconds during the brain imaging.

Zubieta predicted correctly that those people who were able to metabolise dopamine best because both copies of their gene were of the valine form would feel least pain.

"Depending on the genotype you got - which had lowest, intermediate and highest activity - people had a gradation in response," said Zubieta.

In people with two copies of the methionine form of COMT, the dopamine is not cleared fast enough. If this becomes chronic the uncleared dopamine also acts on a second brain pathway regulating pain and stress.

Zubieta said a quarter of the population would be pain sensitive types, a quarter would be more stoic types, and half would be in between.

Journal reference: Science (vol 299, p 1240)