Patients with degenerative disc disease genetically different than those without the condition

Study finds patients with DDD are genetically predisposed to develop chronic pain after injury.

Variations in two pain-modulating genes may predispose some to develop and protect other patients from developing chronic pain associated with lumbar degenerative disc disease, according to results of a prospective, cohort study.

“The implications [of this study] are particularly important for orthopedic physicians because the preponderance of conditions we treat is pain-related,” David H. Kim, MD, associate clinical professor of orthopedic surgery at Tufts University Medical School, Boston, told Orthopedics Today. “We are beginning to understand that the experience of pain is largely determined by genetics. Greater understanding of this relationship could potentially improve success rates in treating everything from degenerative disc disease to hip and knee arthritis, rotator cuff tears, etc.”

Kim and colleagues performed genetic analysis on 100 patients who presented for surgical treatment of lumbar degenerative disc disease (DDD). Patients had to be 18 years or older with moderate to severe low back pain that did not respond to at least 6 months of nonoperative treatment.

Kim presented the study results at the North American Spine Society 23rd Annual Meeting.

The researchers targeted 2 genes that increase chronic pain risk: the catecholamine-O-methyltransferase gene (COMT) and the GTP cyclohydrolase 1 gene (GCH1) because they have appeared to be most strongly associated with development of chronic pain. Pain-protective haplotype

The distribution of four single nucleotide polymorphisms (SNPs) in the GCH1 gene was significantly different in the DDD patient population compared with the general population. Three SNPs were significantly under-represented and were consistent with a genetic haplotype that previous research has shown confers protection against development of chronic pain.

“This finding confirms, or at least supports, the hypothesis that this GCH1 pain-protective haplotype may prevent the development of chronic pain following back or spinal injury,” Kim said during his presentation.

In addition, they found that a GCH1 allele that is relatively infrequent in the general population was over-represented in the DDD-patient population.

“Although more study is required before firm conclusions can be drawn, this finding suggest that there may also be a haplotype that is responsible for conferring increased risk for the development of chronic pain associated with degenerative disc disease,” he said.

Patients presenting for surgery for DDD were genetically different from the general population, Kim said. “They appeared to have a significantly greater percentage of the low pain tolerance forms of these two genes and genes that predispose individuals to develop chronic pain following injury.”

Likewise, “The gene variations we are studying appear to predispose patients to, and protect them from, developing chronic pain associated with lumbar degenerative disc disease,” he said.

Kim believes that there will be perhaps a dozen genes of significance that can be used to screen patients for surgical treatment.

“It will allow us to predict more accurately the likelihood of successful treatment in patients who are presenting with chronic back pain and a presumed diagnosis of DDD,” he said. “Ultimately, we hope to improve on what has long been at best an approximate 75% success rate in surgical treatment of these patients.”

For more information:
David H. Kim, MD, can be reached at 125 Parker Hill Ave., Boston, MA 02120; 617-754-5595; e-mail: dhkim@caregroup.harvard.edu. He is a consultant for Medtronic, DePuy, Stryker, Zimmer, Synthes and Zoll. His institution receives research grants from New England Baptist Hospital and the North American Spine Society.

Reference:
Kim DH, Martha J, Banco R, et al. Polymorphic variation of the COMT and GCH1 genes in patients undergoing surgical treatment for lumbar degenerative disc disease. Paper # 62. Presented at the North American Spine Society 23rd Annual Meeting. Oct. 15-18, 2008. Toronto.