Pain tolerance may be linked to genes

By Bridgett Novak

NEW YORK (Reuters Health) - Why do people perceive and tolerate pain differently? A study scheduled for presentation April 30 at the annual meeting of the American Academy of Neurology in Philadelphia shows that certain genes may hold the key.

Researchers retrospectively evaluated 2,721 people with chronic pain (primarily musculoskeletal pain, including low back/lumbar pain) who were taking prescription opioids. Each patient was asked to rate their pain from zero to 10 on a visual analog scale (Pain VAS). Those who rated it a zero were eliminated from the study.

Those who gave their pain a one, two or three ranking were deemed to have low pain; four, five and six were classified as moderate pain; and scores of seven through 10 were considered high pain.

All participants were genotyped using a real-time PCR TaqMan assay from Proove Biosciences. The following DNA sequences, or single nucleotide polymorphisms (SNPs), were identified and evaluated using linear regression: DRD1, DRD2, COMT, and OPRK1.

A mutation in DRD1 was 33% more prevalent in the group with low pain than in those with high pain. The COMT and OPRK1 gene variants were 25% and 19% more prevalent in the moderate pain group, respectively, than in the group with high pain. Conversely, the DRD2 variant was 25% more common in the high pain group than in people with moderate pain.

Interestingly, though not part of this particular study, all four genes have also been associated with a higher incidence of alcohol abuse, as well as with depression and other mood disorders. Three of the four (excluding the opioid receptor or the OPRK1 gene) have been linked to a higher incidence of drug abuse.

"Chronic pain can affect every part of life. Finding genes that may play a role in pain perception could provide a target for developing new therapies and help physicians better understand their patients' perceptions of pain," said Dr. Tobore Onojjighofia, one of the researchers and a member of the staff at Proove Biosciences, in a press release about the study's findings.

In terms of new medications, Dr. Daniel Schwarz, who also participated in the study and is the medical director of Proove Bioscience's Pain & Addiction division, said in an email: "There may be other medications that may be able to block excess dopamine in the nucleus accumbens, aside from beta blocker drugs. For instance, current research is being done using analogs that can modify receptors. Several studies have shown certain agonists can help treat addiction, which we extrapolate to pain perception based upon the same mesolimbic 'reward' system. And we have learned that patients with OPRM1 118G variants do better with naltrexone treatment for alcohol abuse. New drugs using the delta opioid receptor and the nociceptin/orphanin FQ (NOP) or 4th type of opioid receptor are showing promise in pain management."

Dr. Jennifer Molano, assistant professor in the Department of Neurology and Rehabilitation Medicine at the University of Cincinnati College of Medicine, agreed that "future studies could use this information to determine the extent to which medications and/or non-pharmacological interventions may be beneficial in those with chronic pain."

She added the following caveat, however: "Pain is a complex phenomenon, and pain perception may be influenced by other factors, including mood, stress, and sleep. In addition to genetics, all of these other contributing factors should be considered in optimally treating patients with chronic pain."

This study was supported by Proove Biosciences, Inc.

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