Chronic pain conditions have frustrated doctors and patients alike for decades. Patients suffering from fibromyalgia have perplexed the medical community so intensely that many are written off as hypochondriacs and drug seekers, leaving them frustrated and without relief.
It has long been assumed that there is some genetic component to fibromyalgia and a tendency toward chronic pain. Research has recently uncovered some candidates for this genetic connection, and today we will focus on one of these: COMT.
COMT is Catechol-o-methyltransferase, the enzyme responsible for regulation of availability of catecholamines (an important group of chemical messengers in your body) through a biochemical process called methylation (which I also discussed in my last blog post). COMT is known to play a key role in maintaining appropriate sympathetic tone (whether your nervous system is in flight or flight mode versus rest and digest mode), mood, and inflammation. All three of these processes have a huge influence on pain! [1]–[4]
There is a well-known variant of this gene that has been implicated by the research as related to a number of painful conditions: Val158Met. This SNP (a single nucleotide polymorphism, or a small change in the gene’s code), has been found to decrease the efficiency of the enzyme coded for by the gene by 25-40%. And when an enzyme is worse at doing its job, you can feel it slacking off. Numerous studies have found a strong association between this SNP and fibromyalgia, chronic pain and migraines, along with increased post-surgical pain and even TMJ. This may give us insight into the origins of these conditions, allowing us to target them at their core! [5], [6]
Researchers have also found that when your genome contains a combination of SNPs in both COMT and MTHFR (an enzyme crucial to all methylation) the risk of fibromyalgia increases even more [4], [7]. Further evidence supporting the relationship is provided by another study that found elevated levels of Homocysteine in the cerebrospinal fluid of patients with fibromyalgia.[8] As I talked about in my last blog post, a defect in MTHFR is an important cause of elevated homocysteine.
This gives us a solid foundation on which to suggest that supporting methylation as a whole and supporting the weak COMT enzyme can lead to an improvement in these conditions by correcting one of the underlying causes. The standard American lifestyle does the exact opposite of support these biological processes, so after diet and lifestyle modifications, many suffering from complications of these SNPs have seen huge improvements. Changes as simple as moving to a whole foods based diet, finding better ways to manage stress, and avoiding toxic exposures have given many sufferers long over-due relief.
For more information on how methylation affects your health, and how you can affect your methylation, stay tuned for the next installment in this series (like us on Facebook to be the first to see it!) and register for my upcoming webinar, Naturopathic Genetic Analysis – Individualizing Natural Wellness, for an in depth look at the diet and lifestyle changes you can make right now to improve your health!
[1] O. Kambur and P. T. Männistö, “Catechol-O-methyltransferase and pain.,” Int. Rev. Neurobiol., vol. 95, pp. 227–79, 2010.
[2] A. Tammimäki and P. T. Männistö, “Catechol-O-methyltransferase gene polymorphism and chronic human pain: a systematic review and meta-analysis.,” Pharmacogenet. Genomics, vol. 22, no. 9, pp. 673–91, Sep. 2012.
[3] M. Martínez-Jauand et al., “Pain sensitivity in fibromyalgia is associated with catechol-O-methyltransferase (COMT) gene.,” Eur. J. Pain, vol. 17, no. 1, pp. 16–27, Jan. 2013.
[4] S. B. Smith et al., “Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme activity and pain.,” Pain, vol. 155, no. 11, pp. 2390–9, Nov. 2014.
[5] Y. H. Lee, J.-H. Kim, and G. G. Song, “Association between the COMT Val158Met polymorphism and fibromyalgia susceptibility and fibromyalgia impact questionnaire score: a meta-analysis.,” Rheumatol. Int., vol. 35, no. 1, pp. 159–66, Jan. 2015.
[6] H. Cohen, L. Neumann, Y. Glazer, R. P. Ebstein, and D. Buskila, “The relationship between a common catechol-O-methyltransferase (COMT) polymorphism val(158) met and fibromyalgia.,” Clin. Exp. Rheumatol., vol. 27, no. 5 Suppl 56, pp. S51-6.
[7] A. Inanir, S. Yigit, A. Tekcan, F. A. Pinarli, S. Inanir, and N. Karakus, “Angiotensin converting enzyme and methylenetetrahydrofolate reductase gene variations in fibromyalgia syndrome.,” Gene, vol. 564, no. 2, pp. 188–92, Jun. 2015.
[8] B. Regland, M. Andersson, L. Abrahamsson, J. Bagby, L. E. Dyrehag, and C. G. Gottfries, “Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome.,” Scand. J. Rheumatol., vol. 26, no. 4, pp. 301–7, 1997.