Evidence map›Paper›PMID 36235736›Full record

Trial reportNutrients2022

The Effect of Palmitoylethanolamide on Pain Intensity, Central and Peripheral Sensitization, and Pain Modulation in Healthy Volunteers-A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial.

Kordula Lang-Illievich, Christoph Klivinyi, Gudrun Rumpold-Seitlinger, Christian Dorn, Helmar Bornemann-Cimenti

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Nutrients, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 5% of its field
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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. Effect ofNutrients · 2026
    Trial
  3. The Effect ofNutrients · 2026
    Trial
  4. Trial
  5. Trial
  6. Article
  7. Article
  8. Review
  9. Allodynia: A Review Article.Current pain and headache reports · 2025
    Review
  10. Review
  11. Review
  12. Multi-regional sequential pain syndrome.Frontiers in neurology · 2025
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. What Do We Know about Nociplastic Pain?Healthcare (Basel, Switzerland) · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Kordula Lang-IllievichDepartment of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, 8036 Graz, Austria.
Christoph KlivinyiDepartment of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, 8036 Graz, Austria.
Gudrun Rumpold-SeitlingerDepartment of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, 8036 Graz, Austria.
Christian DornDepartment of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, 8036 Graz, Austria.
Helmar Bornemann-CimentiDepartment of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, 8036 Graz, Austria.ORCID 0000-0002-1201-3752
Medical University of Graz · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Palmitoylethanolamide (PEA) is marketed as a "dietary food for special medical purposes". Its broad-spectrum analgesic, anti-inflammatory, and neuroprotective effects make PEA an interesting substance in pain management. However, the underlying analgetic mechanisms have not yet been investigated in humans. The aim of our study is to provide a deeper understanding of the involved mechanisms, which is essential for differentiating therapeutic approaches and the establishment of mechanism-based therapeutic approaches. In this randomized, placebo-controlled, double-blinded crossover trial, 14 healthy volunteers were included. PEA (3 × 400 mg per day) or placebo were taken for 4 weeks. Our study investigated the mode of action of PEA using an established pain model, "Repetitive phasic heat application", which is well-suited to investigate analgesic and anti-hyperalgesic effects in healthy volunteers. Parameters for peripheral and central sensitization as well as for pain modulation were assessed. Repetitive heat pain was significantly decreased, and the cold pain tolerance was significantly prolonged after the PEA treatment. The pressure pain tolerance and the conditioned pain modulation were increased after the PEA treatment. The wind-up ratio and the average distance of allodynia were significantly decreased after the PEA treatment. The heat pain tolerance was significantly higher after the PEA treatment. The present study has demonstrated that PEA has clinically relevant analgesic properties, acting on both peripheral and central mechanisms as well as in pain modulation.

Indexed as

Neuroprotective AgentsAmidesAnalgesicsAnti-Inflammatory AgentsCross-Over StudiesDouble-Blind MethodEthanolaminesHealthy VolunteersHumansHyperalgesiaPainPain MeasurementPalmitic AcidsAmidesAnalgesicsAnti-Inflammatory AgentsEthanolaminesNeuroprotective AgentspalmidrolPalmitic Acidsallodyniacentral sensitizationconditioned pain modulationhyperalgesiapainpalmitoylethanolamideperipheral sensitizationwind-up

Identifiers

PMID36235736
PMCPMC9570726
OpenAlexW4303962059

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.