In the evolving landscape of orthopaedic manual therapy, the intersection of genetics and pain science has become a focal point for researchers aiming to explain variance in treatment outcomes. Specifically, the catechol-O-methyltransferase (COMT) gene and its Val158Met polymorphism have drawn significant attention due to their role in regulating catecholamine levels and modulating pain sensitivity. For physiotherapists treating Carpal Tunnel Syndrome (CTS), the question arises: does a patient’s genetic profile influence their response to manual therapy or surgery?
The Intersection of Genetics and Pain Modulation
The Val158Met polymorphism determines the activity of the COMT enzyme, which is crucial for metabolizing neurotransmitters like dopamine, epinephrine, and norepinephrine. Previous studies have suggested that individuals with the Met/Met genotype may have reduced COMT activity, potentially leading to lower pain thresholds and higher sensitivity. Conversely, the Val/Val genotype is often associated with higher enzyme activity and greater pain tolerance.
Given that central sensitization is a known component of chronic CTS, researchers hypothesized that these genetic variations might predict who recovers well and who struggles with persistent pain following intervention. To test this, Fernández-de-Las-Peñas et al. (2018) conducted a secondary analysis of a randomized controlled trial (RCT) involving 120 women with CTS.
Study Methodology: Manual Therapy vs. Surgery
The study compared two distinct interventions. One group (n=60) underwent decompression surgery, while the other group (n=60) received three sessions of manual therapy. The manual therapy protocol was comprehensive, including soft tissue mobilization and specific desensitization maneuvers directed at the central nervous system. This approach aligns with modern orthopaedic manipulation strategies that address both peripheral and central pain mechanisms.
Researchers genotyped the participants to classify them as Val/Val, Val/Met, or Met/Met. Primary outcomes focused on pain intensity (mean and worst pain), while secondary outcomes utilized the Boston Carpal Tunnel Questionnaire to assess function and symptom severity. Assessments were taken at baseline and followed up at 1, 3, 6, and 12 months.
The Verdict: Genetics Did Not Dictate Outcome
The results of this 12-month follow-up offer a clear message to clinicians. With a 92% completion rate, the statistical analysis revealed no significant interaction between the Val158Met genotype and clinical outcomes. Whether a patient possessed the “pain-sensitive” Met/Met alleles or the “pain-tolerant” Val/Val alleles, their response to treatment remained statistically similar.
Both the surgery group and the manual therapy group demonstrated improvements in pain and function, but these improvements were not gated or enhanced by the COMT genotype. The researchers found no association with mean pain intensity, worst pain intensity, or functional deficits.
Clinical Implications for Physiotherapists
For the practicing physiotherapist, these findings are highly clinically relevant and encouraging. They suggest that the efficacy of manual therapy—specifically protocols including CNS desensitization—is robust and not easily undermined by this specific genetic predisposition. While the search for biomarkers in pain management continues, clinicians can proceed with confidence that a patient’s COMT status is unlikely to be a barrier to recovery in CTS cases managed with appropriate manual therapy or surgical intervention.
References
Fernández-de-Las-Peñas, C., Ambite-Quesada, S., Fahandezh-Saddi Díaz, H., Paras-Bravo, P., Palacios-Ceña, D., & Cuadrado, M. L. (2018). The Val158Met polymorphism of the catechol-O-methyltransference gene is not associated with long-term treatment outcomes in carpal tunnel syndrome: A randomized clinical trial. PLoS ONE, 13(10), e0205574.
