Evidence map›Paper›PMID 41324391›Full record

ArticlePain2026

The contribution of baseline circulating endocannabinoids to individual differences in human pain sensitivity: a quantitative sensory testing study.

S A Fatemi, S S Abssy, S L Bourke, K B Murray, C Kyeremaa-Adjei, L Honigman, N Mohabir, C Sexton, M A Cormie, R Tomin and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Pain, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

S A FatemiCentre for Multimodal Sensorimotor and Pain Research, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.
S S AbssyCentre for Multimodal Sensorimotor and Pain Research, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.ORCID 0009-0001-7044-3566
S L BourkeCentre for Multimodal Sensorimotor and Pain Research, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.ORCID 0000-0003-3995-8286
K B MurrayPharmacology and Therapeutics, School of Pharmacy and Medical Sciences, Institute for Health Discovery and Innovation, Institute for Clinical Trials, University of Galway, Galway, Ireland.
C Kyeremaa-AdjeiPharmacology and Therapeutics, School of Pharmacy and Medical Sciences, Institute for Health Discovery and Innovation, Institute for Clinical Trials, University of Galway, Galway, Ireland.
L HonigmanCentre for Multimodal Sensorimotor and Pain Research, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-3338-4675
N MohabirCentre for Multimodal Sensorimotor and Pain Research, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-4914-9485
C SextonCentre for Multimodal Sensorimotor and Pain Research, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-7422-1004
M A CormieCentre for Multimodal Sensorimotor and Pain Research, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.ORCID 0009-0008-5121-9228
R TominCentre for Multimodal Sensorimotor and Pain Research, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.ORCID 0009-0003-4893-2712
I BoileauCentre for Addiction and Mental Health, Toronto, ON, Canada.ORCID 0000-0002-9901-1484
L Y AtlasNational Center For Complementary and Integrative Health, National Institutes of Health, Bethesda, MD, United States.
D P FinnPharmacology and Therapeutics, School of Pharmacy and Medical Sciences, Institute for Health Discovery and Innovation, Institute for Clinical Trials, University of Galway, Galway, Ireland.
M MoayediCentre for Multimodal Sensorimotor and Pain Research, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-7324-2540

Funding

Canada Research Chairs Pain NeuroImagingCIHR 183703Faculty of Dentistry, University of Toronto Harron Fund AwardGovernment of Ontario Ontario Graduate ScholarshipIrish Research Council GOIPG/2019/3945Natural Sciences and Engineering Research Council of Canada CGS-MNIH HHS ZIA-AT000030University of Toronto Centre for the Study of Pain Pain Scientist
6 · The paper itself

Abstract

abstractThe endocannabinoid (eCB) system comprises cannabinoid receptors; endogenous ligands, including anandamide (AEA), 2-arachidonoylglycerol (2-AG); and related N -acylethanolamines (NAEs), N- palmitoylethanolamide (PEA), and N- oleoylethanolamide (OEA); and metabolizing enzymes (eg, fatty acid amide hydrolase [FAAH]). The eCB system modulates nociceptive circuits in rodents. In humans, the FAAH C385A polymorphism is associated with reduced pain sensitivity, suggesting eCB tone contributes to individual pain differences, but this has yet to be tested. Here, we determined whether the eCB system is associated with somatosensory and pain sensitivity measured with quantitative sensory testing (QST) in 91 healthy participants (39 males, 52 females). We tested 3 hypotheses: (1) FAAH C385A polymorphism, cannabis use, and sex affect serum eCB/NAE concentrations; (2) FAAH C385A carriers show altered pain sensitivity vs noncarriers; and (3) baseline serum eCB/NAE concentrations are associated with QST measures. eCB/NAE concentrations were not statistically different based on sex ( P > 0.05), FAAH genotype ( P > 0.05), or cannabis use ( P > 0.05). To address collinearity of AEA, OEA, and PEA, we performed a principal components analysis, which identified a single component of FAAH substrates. Linear regressions found that FAAH genotype did not affect QST measures and that baseline 2-AG and FAAH substrate concentrations were not associated with QST measures, except pressure pain thresholds (PPT; P = 0.003), which were associated with AEA and OEA. Baseline eCB/NAE levels and FAAH genotype are not associated with the outcome measures of standard QST tests that rely on point estimates in healthy adult humans; nonetheless, circulating FAAH substrate levels were associated with PPT.

Indexed as

EndocannabinoidsIndividualityPainPain ThresholdAdultAmidohydrolasesArachidonic AcidsEthanolaminesFemaleHumansMaleMiddle AgedPain MeasurementYoung AdultAmidohydrolasesArachidonic AcidsEndocannabinoidsEthanolaminesFatty-acid amide hydrolasePainQuantitative sensory testingSex differences

Identifiers

PMID41324391

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.