This is an interesting natural substance which shows great promise in treating chronic pain, It is much safer with less harmful side effects than most of the other painkillers used. It is available on prescription from someone familiar with its use. It costs about $100 for 2-3 months, so is not cheap.

J Pain Res. 2012; 5: 437–442. Published online 2012 Oct 26. doi:  [10.2147/JPR.S32143]PMCID: PMC3500919PMID: 23166447

Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series

Jan M Keppel Hesselink and Thecla AM HekkerAuthor informationCopyright and License informationDisclaimerThis article has been cited by other articles in PMC.Go to:

Video abstract

Download video file.^{(103M, avi)}

VideoKeywords: endocannabinoid, chronic, neuropathy, chemotherapy, itch, polyneuropathyGo to:

Abstract

Palmitoylethanolamide (PEA), an endogenous fatty acid amide, has been demonstrated to bind to a receptor in the cell nucleus – the peroxisome proliferator–activated receptor – and performs a great variety of biological functions related to chronic and neuropathic pain and inflammation, as has been demonstrated in clinical trials. These include peripheral neuropathies such as diabetic neuropathy, chemotherapy-induced peripheral neuropathy, carpal tunnel syndrome, sciatic pain, osteoarthritis, low-back pain, failed back surgery syndrome, dental pains, neuropathic pain in stroke and multiple sclerosis, chronic pelvic pain, postherpetic neuralgia, and vaginal pains. Probably due to the fact that PEA is an endogenous modulator as well as a compound in food, such as eggs and milk, no serious side effects have been reported, nor have drug–drug interactions. This article presents a case series describing the application and potential efficacy and safety of PEA in the treatment of various syndromes associated with chronic pain that is poorly responsive to standard therapies.Go to:

Introduction

Chronic pain and neuropathic pain are indications for which there is high need in the clinic, and as Loeser put it boldly recently, “… the lack of evidence for the outcomes of most of the things providers do for patients” is one of the preeminent crises in pain management today.1 Indeed, many patients suffering from neuropathic conditions have pain that is refractory to existing treatments.2 In this context, palmitoylethanolamide (PEA), an endogenous fatty acid amide, is emerging as a novel agent in the treatment of pain and inflammation. The compound was used many decades ago in some countries, but due to a lack of insight in its mechanism of action, interested weaned. Since the 1990s, interest has surged again due to the discovery of its effects in many different animal paradigms for pain and chronic inflammation. It is classified as a food for medical purposes or as a diet supplement in various countries of Europe. PEA has shown efficacy in many different preclinical animal models for chronic and neuropathic pain, and most importantly is effective in reducing pain in man in various clinical trials in a variety of pain states.3 The main target of PEA is thought to be the peroxisome proliferator-activated receptor alpha (PPAR-α).4 This receptor is a regulator of gene networks which control pain and inflammation5, probably by switching off the nuclear factor-kappaB signaling cascade,4–7 a key element in the transcription of genes for proinflammatory mediators (cytokine, chemokines, nitric oxide). PEA also has affinity to cannabinoid-like G protein-coupled receptors GPR55 and GPR119.8 PEA can influence ion channels (eg, potassium channels) that play a role in pain.9 Furthermore, PEA might desensitize transient receptor potential cation channel subfamily V member 1 channels on sensory neurons.10,11

PEA anti-inflammatory actions allowing for a reduction of peripheral and central sensitization are mediated via both neuronal and nonneuronal cells. The latter comprise glia (in particular microglia, which are the brain’s macrophages) as well as peripheral and central mast cells.12–15 This profile of PEA may thus explain its broad potential in treating many different disorders related to pain and inflammation.16

Based on this knowledge, we selected a number of pain treatment-resistant patients and started adding PEA to the analgesic treatment regime. This paper presents seven different clinical cases, six of which showed a clear beneficial effect of PEA