“Our study investigated the mode of action of PEA using an established pain model in healthy volunteers, providing a deeper understanding of the involved mechanisms, which is essential for differentiating therapeutic approaches and the establishment of mechanism-based therapeutic approaches,” wrote the researchers from the University of Graz, which funded the study.
Published in the Nutrients journal’s special issue “Frontier of Diet and Chronic Disease: New Progress on Fibrotic Diseases Inflammation and Pain”, the study presents PEA as an alternative to frequently used analgesic drugs such as NSAIDs and opioids.
PEA and pain
First isolated in soybeans, egg yolk and peanut meal, PEA is a cannabimimetic compound produced naturally in the human body in response to injury and stress.
“The broad-spectrum analgesic, anti-inflammatory and neuroprotective effects make PEA an interesting substance in pain management,” the researchers stated.
“A recent meta-analysis of studies in which PEA was used as a treatment for neuropathic or chronic pain proved its clinical efficacy. However, the underlying analgesic mechanisms have not yet been investigated in humans.”
To explore the modes of action of PEA, the researchers differentiated three pivotal mechanisms including peripheral sensitization, central sensitization and pain modulation.
The randomized, placebo-controlled, double-blinded crossover trial administered 400 mg of PEA or a placebo to 14 healthy volunteers three times a day over four weeks. Dutch company Innexus Nutraceuticals provided the PEA, and the placebo was manufactured by the Medical University of Graz’s institutional pharmacy.
After the 28-day test period, the researchers measured the effects on conditioned pain modulation, pain pressure threshold and cold pain tolerance against initial baseline measurements. The validated “repetitive phasic heat application” pain model was used to induce short-term peripheral and central sensitization and investigate analgesic and anti-hyperalgesic effects. Following an 8-week washout period, new baseline measurements were taken before participants crossed over to the other study intervention for 28 days.
Participants in the PEA group showed a significant decrease in repetitive heat pain, wind-up ratio and average distance of allodynia (pain caused by a normally painless stimulus), as well as a significant prolonged cold pain tolerance and an increase in pressure pain and heat pain tolerance.
“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,” the researchers concluded.
The study proposed that further trials explore the efficacy in patients with reduced conditioned pain modulation, in people suffering from depression or in situations like fibromyalgia in which central sensitization develops.
“Our data also suggest the effectiveness of PEA as a preventive analgesic treatment,” the researchers added. “This approach may be further explored in future trials, e.g., in the management and prevention of persistent postoperative pain.”
Nutrients 2022, 14(19), 4084
“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”
Authors: Kordula Lang-Illievich et al.