How is "Transition from Acute to Chronic Low Back Pain" encoded by the genome?
Lower back pain (LBP) is responsible for one-third of work-related disability claims, is one of the top 10 most expensive conditions to treat in the United States, and affects nearly 1 in 10 people worldwide. For most individuals with an episode of acute lower back pain (ALBP), the pain resolves within 4 to 6 weeks, and patients regain the ability to resume normal activities. However, an estimated 20% of individuals with acute pain will continue to have pain beyond 12 weeks, described as chronic lower back pain (CLBP). This pain exists at a level that negatively impacts normal activities, functions, and quality of life. The transition from ALBP to CLBP raises the risk of long-term disability and comorbidities, including other pain disorders.
Several factors, including heritability and the environment, contribute to the risk of transitioning from acute pain to chronic pain. Recently, two genes, Catechol-O-Methyltransferase (COMT) and Brain-Derived Neurotrophic Factor (BDNF) have been suggested to be associated with pain processing and pain sensitivity. Researchers hypothesized that the CLBP group would have a higher pain burden early on, increased sensitivity to painful stimulation, and increased frequency of BDNF and COMT risk alleles compared with the ALBP group.
For more understanding of the role of COMT and BDNF in the transition from ALBP to CLBP, 220 participants with recent onset of lower back pain were recruited for this study. The participants’ conditions were monitored until the LBP resolved or until the end of the study at 6 months. Participants who were still experiencing pain at the 6-month visit were classified as CLBP cases. Otherwise, they were classified as ALBP cases. Results showed that CLBP cases reported significantly higher ratings for the pain severity and pain interference subscales of the Brief Pain Inventory (BPI). As for the COMT polymorphism rs4680, more participants who had the GG genotype were distributed in the CLBP group than in the ALBP group when compared to other rs4680 genotypes. Moreover, those with the AA genotype were significantly associated with having a lower cold pain threshold (°C), meaning they were less sensitive to cold pain, at the time of initial recruitment, regardless of whether their pain would resolve quickly or develop CLBP. In addition, the study revealed that COMT expression was independently associated with risk for transition.
The A allele of rs4680 is typically described as the “risk” allele for its associations with lower enzymatic activity, higher dopamine levels, more dopamine in the prefrontal cortex, and higher anxiety and increased pain sensitivity in normal and inflammatory conditions. However, the findings agree with reports that pharmacological inhibition of COMT enzymatic activity, a treatment that mimics the reduced activity seen in the presence of the A allele of rs4860, reverses neuropathic pain in a rat model of spinal nerve ligation. This pattern of results would be expected if early engagement of a neuropathic mechanism contributes to the development of CLBP. Read more about the study here:
https://pubmed.ncbi.nlm.nih.gov/32079998/
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