Three articles on PainSci cite Khoury 2019: 1. Anxiety & Chronic Pain 2. 35 Surprising Causes of Pain 3. A Rational Guide to Fibromyalgia
PainSci commentary on 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 wherever 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).
~ Paul Ingraham
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:
- No long-term effects after a three-week open-label placebo treatment for chronic low back pain: a three-year follow-up of a randomized controlled trial. Kleine-Borgmann 2022 Pain.
- Exercise and education versus saline injections for knee osteoarthritis: a randomised controlled equivalence trial. Bandak 2022 Ann Rheum Dis.
- Association of Lumbar MRI Findings with Current and Future Back Pain in a Population-based Cohort Study. Kasch 2022 Spine (Phila Pa 1976).
- A double-blinded randomised controlled study of the value of sequential intravenous and oral magnesium therapy in patients with chronic low back pain with a neuropathic component. Yousef 2013 Anaesthesia.
- Is Neck Posture Subgroup in Late Adolescence a Risk Factor for Persistent Neck Pain in Young Adults? A Prospective Study. Richards 2021 Phys Ther.