Bolest

2017 systematic meta-analysis involving 10 studies

• Data from 786 patients receiving PEA for pain-related indications and 512 controls
• PEA was found to be associated with pain reduction significantly greater than observed in controls (P < 0.001)

Congenital insensitivity to pain

• 2019, significant increases in fatty acid amides including
• PEA,
• Arachidonoylethanolamide,
• Oleoylethanolamide
• In a Scottish woman with a previously undocumented variant of Congenital insensitivity to pain
• Result of a combination of a hypomorphic single nucleotide polymorphism of fatty acid amide hydrolase (FAAH)
• Alongside a mutation of the pseudogene, FAAH-OUT
• Pseudogene was previously considered to be non-coding DNA
• FAAH-OUT was found to be capable of modulating the expression of FAAH,
• Making it a possible future target for novel analgesia/anxiolytic drug development

Analgetické při chronické bolesti

• N-acylethanolamines such as PEA often act as signaling molecules
• Activating receptors and regulating a variety of physiological functions
• PEA is known to activate intracellular, nuclear and membrane-associated receptors
• Inflammatory cascade and chronic pain states
• Endocannabinoid lipids like PEA are widely distributed in nature, in a variety of plant, invertebrate, and mammalian tissues
• Lipid amides of the N-acylethanolamine type, such as PEA
• Potential prototypes of naturally occurring molecules capable of modulating mast cell activation
• Autocoid synthesized on-demand in response to injury
• Mast cell appeared to be an important target for the anti-inflammatory activity of PEA
• Often found in proximity to sensory nerve endings
• Degranulation can enhance the nociceptive signal
• Considered to be pro-inflammatory and pro-nociceptive
• Decrease in pain sensitivity during and after sport
• Comparable to the endogenous opiates (endorphines)

Neuropathic pain

THC

• Proven to be effective in neuropathic pain states

PEA in two models of acute and persistent pain

• Seemed to be explained at least partly via the de novo neurosteroid synthesis

Chronic granulomatous pain and inflammation model

• PEA could prevent nerve formation and sprouting, mechanical allodynia,
• PEA inhibited dorsal root ganglia activation
• Hallmark for winding up in neuropathic pain
• PEA as an analgesic and anti-inflammatory molecule
• PEA inhibits the release of both preformed and newly synthesised mast cell mediators
• histamine and TNF-alpha
• PEA + its analogue adelmidrol (di-amide derivative of azelaic acid)
• Can both down-regulate mast cells
• PEA reduces the expression of
• Cyclooxygenase-2 (COX-2)
• Inducible nitric oxide synthase (iNOS)
• Prevents IkB-alpha degradation
• Prevents p65 NF-kappaB nuclear translocation
• Related to PEA as an endogenous PPAR-alpha agonist
• Treatment of neuropathic pain and related disorders based on overactivation of glia and glia-related cells
• Diabetes and glaucoma
• Central sensitization

Sciatic pain

2015 analysis of a double blind placebo controlled study of PEA

• Numbers Needed to Treat was 1.5.

Model of visceral pain (inflammation of the urinary bladder)

• PEA was able to attenuate the viscero-visceral hyper-reflexia induced by inflammation of the urinary bladder
• Explored in the painful bladder syndrome

Turpentine-induced urinary bladder inflammation in the rat

• PEA also attenuated a referred hyperalgesia in a dose-dependent way

Chronic pelvic pain in patients

• Seem to respond favourably to a treatment with PEA