PainSci summary of Khoury 2019: ?This page is one of thousands in the PainScience.com bibliography. It is not a general article: it is focused on a single scientific paper, and it may provide only just enough context for the summary to make sense. Links to other papers and more general information are provided at the bottom of the page, as often as possible.
This study strongly linked systemic sensory sensitization — not just pain, but all kinds of body sensations — to a glitchy gene that causes low levels of serotonin in 90 chronic pain patients. Uncomfortable awareness of all kinds of sensation is a well-known but previously unexplained companion of chronic widespread pain, but most healthcare professionals have assumed that it is driven by psychological hypervigilance and is a prominent feature of the so-called “fibromyalgia personality.” This research tells a different story: a clear correlation with a genetic malfunction of an enzyme, which significantly slows down production of the neurotransmitter serotonin.
For a much more detailed exploration of these results, see A genetic defect that exaggerates all sensations (including pain).
original abstract †Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.
OBJECTIVE: Heightened somatic symptoms are reported by a wide range of patients with chronic pain and have been associated with emotional distress and physical dysfunction. Despite their clinical significance, molecular mechanisms leading to their manifestation are not understood.
METHODS: We used an association study design based on a curated list of 3,295 single nucleotide polymorphisms mapped to 358 genes to test somatic symptoms reporting using the Pennebaker Inventory of Limbic Languidness questionnaire from a case-control cohort of orofacial pain (n = 1,607). A replication meta-analysis of 3 independent cohorts (n = 3,189) was followed by functional validation, including in silico molecular dynamics, in vitro enzyme assays, and measures of serotonin (5-HT) plasma concentration.
RESULTS: An association with the T allele of rs11575542 coding for an arginine to glutamine substitution in the L-aromatic amino acid decarboxylase (AADC) enzyme was replicated in a meta-analysis of 3 independent cohorts. In a combined meta-analysis of all cohorts, this association reached p = 6.43 × 10-8 . In silico studies demonstrated that this substitution dramatically reduces the conformational dynamics of AADC, potentially lowering its binding capacity to a cofactor. in vitro enzymatic assays showed that this substitution reduces the maximum kinetic velocity of AADC, hence lowering 5-HT levels. Finally, plasma samples from 90 subjects showed correlation between low 5-HT levels and heightened somatic symptoms.
INTERPRETATION: Using functional genomics approaches, we identified a polymorphism in the AADC enzyme that contributes to somatic symptoms through reduced levels of 5-HT. Our findings suggest a molecular mechanism underlying the pathophysiology of somatic symptoms and opens up new treatment options targeting the serotonergic system.
- “Genome-wide association study of multisite chronic pain in UK Biobank,” Keira J A Johnston, Mark J Adams, Barbara I Nicholl, Joey Ward, Rona J Strawbridge, Amy Ferguson, Andrew M McIntosh, Mark E S Bailey, and Daniel J Smith, PLoS Genet, 2019.
Specifically regarding Khoury 2019:
This page is part of the PainScience BIBLIOGRAPHY, which contains plain language summaries of thousands of scientific papers & others sources. It’s like a highly specialized blog. A few highlights:
- Relationships Between Sleep Quality and Pain-Related Factors for People with Chronic Low Back Pain: Tests of Reciprocal and Time of Day Effects. Gerhart 2017 Ann Behav Med.
- Modulation in the elastic properties of gastrocnemius muscle heads in individuals with plantar fasciitis and its relationship with pain. Zhou 2020 Sci Rep.
- Association Between Plantar Fasciitis and Isolated Gastrocnemius Tightness. Nakale 2018 Foot Ankle Int.
- No Added Benefit of Combining Dry Needling With Guideline-Based Physical Therapy When Managing Chronic Neck Pain: A Randomized Controlled Trial. Stieven 2020 J Orthop Sports Phys Ther.
- Effectiveness of customised foot orthoses for Achilles tendinopathy: a randomised controlled trial. Munteanu 2015 Br J Sports Med.