Back pain is most commonly linked to long-term wear and tear on an individual’s discs and joints. However, with advances in genomic research efforts, a better understanding of the mechanisms of back pain has led researchers to believe there may be an underlying genetic predisposition to the condition.
The genetics of pain is extremely complex, and the current evidence in involvement of various pain pathways has been studied most extensively using animal models.
According to Sabu James, MD, of the National Health Services in Lanarkshire, Scotland, more evidence is needed in humans. Currently available data are the result of genome-wide association studies (GWAS), twin studies, and looking at single nucleotide polymorphisms in susceptible populations.
“Even the recent chronic pain meeting at The Sanger Institute in Cambridge, focusing on the ‘genetic’ basis of chronic pain, failed to establish any strong basis genetics play in the onset and perpetuation of chronic neuropathic pain in humans. There are tantalizing hints, but we need more basic research and conclusive evidence,” said James.
Efforts to Identify Genes Involved in Back Pain
Frances MK Williams, PhD, of King’s College London in the United Kingdom and colleagues found that intervertebral disc degeneration, which was always thought to be linked to occupation, is surprisingly heritable. According to these research efforts, this means that 80% of the variation in an individual’s worn discs maybe controlled through genetic factors.
In one study, Williams and colleagues used a GWAS approach to identify potential candidate genes involved in back pain and lumbar disc degeneration (LDD). Researchers looked for associations across the whole genome without any prior expectation of which genes might be implicated. The investigators found a novel gene, PARK2, which was not previously implicated in LDD.1
“There has been no prior knowledge of the PARK2 gene being involved in disc metabolism. It may be pointing us in the direction of alternative cell biology to account for the wear and tear on discs,” says Williams. “Although our finding is exciting, it won’t have immediate clinical impact, as it is only one of very many genes likely involved in the development of back pain.” Other limitations of the study were that it included a large sample of patients from different countries who were selected using different approaches and evaluated with different types of imaging.
According to James, this is a problem across studies of back pain. “It’s increasingly difficult to get a homogenous population or cohort for back pain, as there are several variables which can be confounding.”
In another study performed by Williams and colleagues, investigators found musculoskeletal pain reported at different sites of the body may be explained by one single, genetically determined, common pain factor.2 This is in contrast to previous research efforts that found the genetic factors responsible for pain were specific to the anatomical site of pain.
“We are moving increasingly away from studying structure (joint or disc) and into pain genes, believing that people have a propensity to develop chronic pain,” said Williams. “We are involved in a European funded project called Pain-Omics, which looks at acute low back pain and follows people up to see if it becomes chronic. By taking blood tests at baseline and follow-up, and examining them for many ‘omics’ markers, we hope to find a marker that will allow us to predict who is most likely to develop chronic pain.”
Yet the link between back pain and genetics remains unclear due to other confounding factors including environment, comorbid conditions, and multiple genetic contributors. In a systematic review of twin studies, Amabile Dario, MSc, of the University of Sydney in Australia and colleagues, evaluated the relationship between obesity, low back pain, and LDD.
Going forward, research efforts are needed to better understand the basic science of pain mechanisms and the link between genetics and back pain. Identifying genetic markers of pain may help doctors diagnose and treat pain more effectively before the condition becomes chronic.
Overall, according to James,” the key would be to engage patients early in the disease stage, before the pain becomes chronic and they develop ‘bad habits,’ like depending on too many medications, fear, avoidance, prolonged bed rest, relying on wheelchairs, social isolation, depression, etc.”
Medically Reviewed by: Pat F. Bass III, MD, MS, MPH
1. Williams FMK, et al. Novel genetic variants associated with lumbar disc degeneration in north Europeans: A meta-analysis of 4600 subjects. Ann Rheum Dis. 2013; 72: 1141-1148.
2. Williams FMK, et al. Pain reporting at different body sites is explained by a single underlying genetic factor. Rheumatology. 2010; 49 (9): 1753-1755.
3. Dario AB, et al. The relationship between obesity, low back pain and lumbar disc degeneration when genetics and the environment are considered: A systemic review of twin studies. Spine Journal. 2015; Article in Press.