Exploring The Link Between Genetics and Chronic Pain Conditions
Genes may play a role in determining an individual's propensity to develop painful conditions.
Chronic pain syndromes (CPS) are becoming increasingly prevalent in the general population, with up to 30% of individuals developing a chronic pain condition.
These conditions are especially predominant among middle-aged women. However, comprehension of the underlying mechanisms of action tied to these CPS remains unclear, which makes treatment and management difficult for both physicians and patients.
Recent evidence points to a link between genetics and chronic pain conditions. Specifically, some individuals may have a genetic predisposition for chronic pain.1
“It is suggested in some studies that genes play an important role in determining an individual's propensity to develop this pathology,” said Kimberly Plomp, PhD, of the human evolutionary studies program and department of archaeology at Simon Fraser University in Burnaby, British Columbia, Canada.
Potential for Genetic Contribution to Chronic Pain Risk
In one study, Frances M. Williams, PhD, of King's College London in the United Kingdom and colleagues, evaluated a large cohort of twins (n=8,564) characterized for chronic widespread musculoskeletal pain, chronic pelvic pain, migraine, dry eye disease, and irritable bowel syndrome.
The investigators evaluated potential "underlying genetic and environmental factors contributing to chronic pain and the correlation between them." The results of the study provided evidence of shared genetic factors in conditions manifesting chronic pain, including those evaluated. This indicates the potential for a genetic component associated with the conditions. 2
The challenge to uncovering the underlying mechanisms of chronic pain conditions is that often patients are seen and managed by multiple specialists, according to Williams. In addition, research efforts have focused on these conditions separately, though it's likely the shared mechanism underlying these chronic pain conditions is genetic.
“Chronic pain syndromes are seen in lots of different medical specialties. They cluster together in people because of genetic factors. Patients would be better served by greater recognition of this and a more coordinated approach to their management. Similarly, research into the conditions would move along more quickly if the syndromes were considered together,” said Williams. Going forward, Williams is urging a more collaborative approach both from a clinical perspective and from a research standpoint.
Complexity of Pain Makes Genetic Contribution Difficult to Identify
The risk for chronic pain is complex and likely associated with various genetic factors. According to Antonio Montes, MD, of the department of anesthesiology, Universitat Autònoma de Barcelona in Spain, candidate gene testing in humans has provided some progress in understanding the heritability of pain.
Applying the genome-wide association methodology also offers a tool for studying the genetic contributions to normal pain response and pain in clinical populations.
In a recent study, Montes and colleagues evaluated functional genetic polymorphisms related to chronic post-surgical pain (CPSP) risk or protection and clinical predictors after three types of surgery: inguinal hernia repair, hysterectomy, and thoracotomy.3
“We did not find any association between the 90 analyzed single nucleotide polymorphisms and CPSP, but we cannot completely exclude the role of genetics in the development of CPSP,” said Montes. “We conclude that the lack of unequivocal confirmation of genetic factors predisposing certain patients to CPSP necessitates our continued reliance on scoring clinical factors – particularly procedure, age and preoperative quality of life and experience of pain – to guide interventions or vigilance against the development of this complication.”
According to Montes, further investigations should focus on genetic and clinical interactions through detailed multifactorial studies, such as epigenetic assessments.
Evolutionary Medicine May Contribute to Clinical Research on Chronic Pain
Other research efforts have focused on evolution as contributing to chronic pain conditions. In one study, Plomp and colleagues aimed to understand the evolutionary contribution to spine development and spinal disease. Specifically, the investigators aimed to identify any relationship between vertebral shape, bipedalism, and the presence of Schmorl's nodes in humans.
The investigators found that humans with Schmorl's nodes had vertebral bodies and pedicles that were closer in shape to chimpanzee vertebrae than were the vertebrae without Schmorl's nodes.4
“We interpreted the results to indicate that some humans have retained a particular vertebral shape from our last common ancestor, which was likely quadrupedal. The vertebral elements [that were] identified – the body and pedicles – play important roles in load bearing during bipedal locomotion. We hypothesize that this ancestral vertebral shape may not adequately buttress the vertebrae and intervertebral discs during the stresses placed on the spine by walking on two legs,” said Plomp. “We hope that this research will one day be able to help identify individuals who may be more prone to developing traumatic or degenerative spinal conditions, and thus aid in the prevention of some back problems.”
Going forward, evolutionary medicine may contribute to the clinical research efforts regarding chronic pain.
Although chronic pain syndromes are increasing in prevalence, an understanding of the underlying mechanisms remains unclear. Genetic factors and evolution appear to contribute to these conditions, but limited research has not yet elucidated this correlation.
According to Williams, research efforts should continue to focus on clarifying the underlying genetic contributions to better understand chronic pain and improve diagnosis and treatment.
Reviewed by: Pat F. Bass III, MD, MS, MPH
1. Williams FMK and Vehof J. Genetic predisposition to chronic pain: from evolutionary advantage to a debilitating disease spectrum? Pain Management. 2014; 4(6): 381-383.
2. Vehof J, et al. Shared genetic factors underlie chronic pain syndromes. Pain. 2014; 155(8): 1562-1568.
3. Montes A, et al. Genetic and clinical factors associated with chronic postsurgical pain after hernia repair, hysterectomy, and thoracotomy: A two-year multicenter cohort study. Anesthesiology. 2015; 122: 1123-1141
4. Plomp KA, et al. The ancestral shape hypothesis: An evolutionary explanation for the occurrence of intervertebral disc herniation in humans. BMC Evolutionary Biology. 2015; 15: 68.