Advances in genetic research could help develop personalized pain medications

In the not too distant future, it may be possible to discern an individual's genetic predisposition to chronic pain conditions and treat them proactively to prevent lifetime afflictions, according to research presented today at the American Pain Society's (www.ampainsoc.org) annual scientific meeting.

In his keynote address to some 2,000 pain clinicians attending the APS conference, noted neuro- genetic researcher Clifford Woolf, MD, PhD, professor of neurology and neurobiology, Harvard Medical School and Children's Hospital Boston, said that advances in genetic research will help identify individuals genetically at risk for developing pain and foster personalized pain medicine.

"We know there is a large genetic component for pain," Woolf told the APS audience," and this eventually will be the key that allows clinicians to learn the answers to basic questions, such as: 'Why does one individual feel more pain than another?', 'Why do some transition to chronic pain and others do not?', and 'Why does one patient respond to one analgesic and not another patient?'"

Published studies, according to Woolf, have shown the genetic risks for several types of pain conditions. Two studies of identical twins exposed to experimental pain stimuli showed heritability rates ranging from 22 percent to 60 percent for various pain sensations. Another study of more than 15,000 twins showed that genetic susceptibility explained 38 percent of lumbar pain, 32 percent of thoracic pain and 39 percent of neck pain.

"Genes will become diagnostics for certain types of pain conditions and identify those at highest risk for developing them," said Woolf. He added that knowing an individual's genetic predisposition for pain, for example, will show who is at high risk for developing chronic pain from herpes zoster virus (shingles) and which surgical patients are likely to have prolonged or even permanent post-operative pain from nerves damaged during surgery.

Woolf explained that further understanding of the genetic basis for pain will lead to breakthrough discoveries for new analgesic drugs. "There are several pain genes that have been isolated based on common polymorphisms or variations in the genes that contribute to the variation in an individual's pain. Some genetic variations are associated with reduced pain and others with enhanced pain" he said. "If someone has a genetic variant that increases pain we may be able to target this with specific drugs to produce analgesia, essentially neutralizing their genetic bad luck, and, if we can mimic with drugs the advantages that those individuals who have pain protective gene variant, this too should help develop new and more efficacious analgesic, spreading their genetic good luck. Basically, it will be possible to develop analgesics for individuals using their genetic information."

Research presented by Woolf shows that acute pain is 50 percent genetic, however, he noted that screening the whole genome is expensive and no studies have been funded yet to explore chronic pain in large numbers of patients with required controls. "We need to find the common genetic mutations responsible for pain enhancement in patients with severe chronic pain and those that serve as pain protectors in persons who develop less or no pain before we can identify who is at risk and develop new treatments for them," he said.

Woolf ended his talk on an optimistic note by saying that treating pain with targeted analgesics on the basis of knowledge of an individual's genetic predisposition to certain pain conditions will likely become standard practice in ten years.