Chronic pain is poorly understood and chronic pain management is one of the most challenging issues facing our medical system. It is estimated that 1 in 5 Canadian adults suffer from chronic pain, which is the number one reason for seeking healthcare, costing our economy roughly $50-$60 billion. This emphasizes the need for research into its causes and for more effective chronic pain management, since current strategies are ineffective. The development of chronic pain is linked to various factors including occupational and physical trauma, psychological distress, and traumatic life events. However, it is still unclear why certain people develop chronic pain as a result of these factors and others do not. Chronic pain is known to be heritable and research is suggesting that a genetic predisposition may underlie its development. Moreover, genes have been identified which play a crucial role in determining response to common pain medications. Thus, recent genetic advances hold promise for identifying the causes of chronic pain, guiding treatments, and could identify new targets for therapeutics.
What causes chronic pain?
Chronic pain can be localized to areas like the back or shoulders or it can be widespread. It is more common for people to have pain at multiple sites and this is the defining feature of fibromyalgia. Individuals with chronic pain often have a hard time maintaining regular activities and 72% of those individuals state that it interferes with normal work. The development of chronic pain is often associated with surgical procedures with 50% of patients left with moderate to severe pain after surgery, and in 10-50% of these individuals acute post-operative pain is followed by persistent pain. Why some individuals develop chronic pain while others do not is unclear. Also, the degree of pain experienced after surgery is known to be highly variable between patients, even under nearly identical circumstances. Determining the causes of chronic pain is difficult, largely because the reporting of pain is subjective, and chronic pain is often found in association with other conditions such as sleep disturbances, mood disorders, cognitive dysfunction and fatigue. However, recent studies are beginning to uncover the genetic basis of chronic pain, which may be useful for identifying individuals who are at risk of developing it and may lead to better chronic pain management.
Animal models have been instrumental in determining the genes involved in chronic pain. For example, studies in mice identified the CACGN2 gene as a candidate that might regulate chronic pain, which was previously shown to be involved in cerebellar function and epilepsy. Furthermore, in breast cancer patients, genetic variations in the CACGN2 gene were shown to be associated with chronic pain after surgery. It has been suggested that other genes that are involved in the amplification of pain and psychological distress are associated with chronic pain disorders. Sensory genes like COMT (catechol-O-methyltransferase), ADRB2 (beta 2 adrenergic receptor) and GCH1 (GTP hydrolase) have all been linked to chronic pain. Additionally, genes that regulate neuroendocrine signalling like HTR2A (serotonin receptor 2A) and SLC6A4 (serotonin transporter) have been associated with mediating the relationship between psychological stress and the development of chronic pain. While variations in these genes have been linked to pain disorders and congenital insensitivity to pain, results have been inconsistent and large-scale follow-up studies are needed. Once validated, these genes may be novel targets for new therapies to improve chronic pain management.
Chronic pain management and genetic testing
Not only do genetic advances hold potential for the development of new therapies, they also can determine how an individual will respond to current therapies for chronic pain management. Common medications including opioids and codeine are ineffective in some individuals or may be associated with serious side effects. Genetic testing of the genes involved in the metabolism of these drugs can determine which medications will be effective, as well as the proper dosage for optimal pain relief. For example, the pain medications codeine, oxycontin and tramadol are converted to morphine by the CYP2D6 enzyme and genetic variations in CYP2D6 are linked to poor response to these medications. Thus, individuals with certain genetic variations in CYP2D6 will experience chronic pain despite taking high doses of these medications. Therefore, individuals whose chronic pain is not managed effectively by current therapies may want to consider genetic testing to determine whether the medications they are taking are compatible with their genetic profile. To determine whether genetic testing can help you more effectively manage your pain, schedule a genetic consultation with GeneYouIn.
If you would like to learn more about genetic testing, continue reading this related blog post: “DNA Testing Cost: What to expect from a $99 DNA test”.
Holliday, K.L. and J. McBeth, Recent advances in the understanding of genetic susceptibility to chronic pain and somatic symptoms. Curr Rheumatol Rep, 2011. 13(6): p. 521-7.
Nissenbaum, J., et al., Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2. Genome Res, 2010. 20(9): p. 1180-90.
The Canadian Pain Society
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