Pain with hernia and treatment with palmitoylethalonamide ( PeaPure)
Heavy neuralgia radiating to the leg is also called sciatica or lumbosacral radiculopathy. Doctors have called this neuritis or neuritis of the sciatic nerve, the Nervus Ischiadicus, for a long time. This old concept has now been given a complete new turn.
Sciatica is caused by mechanic pressure by an intervertebral disc on the beginning of the sciatic nerve, the so-called nerve root within or just outside the vertebral column. Because of that pressure the nerve becomes inflamed and then the pain starts usually quite sudden. Then an inflammation that is maintained by the pressure on that nerve, the hernia, starts.
Sciatica and compression leads to inflammation
In fact it thus is a kind of nerve pressure syndrome or compression syndrome. Namely, between every vertebral disc there in an intervertebral disc, the discus. This disc consists of a mucoprotein jelly-like nucleus that is surrounded by elastic straps.
One then speaks of a disc hernia when the elastic straps tear and the nucleus bulges out and then exercises pressure on the nerve.
With a hernia there often is pain in both the back and a very aggressive radiating pain in the leg, sometimes there only is the radiating pain in the leg and often until in the foot. If the pressure on the nerve increases hemiparaesthesia and paralysis symptoms can occur.
This occurs because the nerve consists of two parts: One part for the senses, the sensible nerve, and one for the muscle function, the motor nerve.A Hernia Nuclei Pulposi (HNP) is a nice term for hernia in popular speech, and is thus is a bulge of the intervertebral disc.Hernias normally originate in the so-called intervertebral discs at the lower lumbar vertebra.
The origin of all this stems from our upright posture: given that because of standing up straight the centre of gravity of the body is right before the fifth lumbar vertebra (L5) all centers of gravity come together in the lower back.
The most common levels of a hernia are therefore the L5-S1 (thus between the lower lumbar vertebra and the sacrum) followed by L4-L5 (fourth or penultimate vertebra and the fifth) and L3-L4. Higher up in the back hernias are less common.
Because of the pressure of the hernia on the nerve the sciatic nerve can thus become irritated and inflamed and that is the reason for the very sharp pain in the leg. We call this phenomenon a radiculopathy.
The chronic inflammation of the nerve: neuritis and radiculitis
Research has shown that the pressure causes an inflammation of the nerve and nerveroot, neuritis or a so-called radiculitis. That neuritis or radiculitis then becomes worse because of a waterfall of chemical inflammatory reactions.
It actually is a local inflammation and that is, as we know, accompanied by the production of all sorts of chemical substances. They have all sorts of nice names, such as prostaglandins and cytokines and they are formed by inflammatory cells such as the mast cells. Nitrogen monoxide (NO), a strong vessel dilator, is also formed with that. Then it slowly becomes an unpleasant situation because the so-called metalloproteinases are liberated; these are enzymes that incite the connective tissue around the nerve to multiply and become hyperactivated.
So, in this whole process, various cell types are activated and recruited to the injury site, including mast cells, macrophages, ﬁbroblasts, neutrophils, and Schwann cells. All these cells release ATP, proinﬂammatory cytokines, chemokine ligand 2 (CCL2), prostaglandins (PGs), and various nerve growth factors, which all contribute to abnormal pain sensitivity in periphery. This inﬂammation than leads to massive cell migration, edema, erythema, pain, hyperalgesia and allodynia. The Glial cells, mast cells and related cells all heighten nerve pain such as sciatica by exciting the neurons that transmit pain signals.
Palmitoylethanolamide and sciatic pain
The vicious circle of inflammation, and increasing pain, pain neurotransmitters and increasing inflammation can be stopped by palmitoylethanolamide (PEA), an endogenous fatty acid amide analogue of the endocannabinoid anandamide.  PEA belongs to an entire new class of pain-killing drugs that are not addictive, and do not have dose limiting side efects, and are stomach friendly.
We will present here a case of severe hernia pain treated with PEA.
In a recent trial in Italy, in more than 600 patients, clear efficacy and good safety was demonstrated for palmitoylethalonamide. In the Netherlands, this was our first hernia patient, we treated with PEA, after Lyrica proved to be ineffective. This correspondent with the negative effect of a recent trial following an enrichment design. 
A medical doctor, former president of a big dutch hospital, suffered from severe neuropathic sciatic pain, painscore 10 minus over 10, without any response on treatment with pregabaline, apart from severe side effects such as confusion and dizziness, treated with palmitoylethanolamide, a body own fatty acid with analgesic properties.
Pain with Sciatica as we will hear from this doctor/patient can impair a normal life and cause excruciating pain. It can and will restrict your ability to walk and maybe the ability to move, as he tells us. Usually the pain is mainly on one side of the body. It will start at the lower back and move its way down the hip and even all the way down to the toes. Palmitoyjethanolamide is an interesting new treatment option, and CNS side effects like dizziness and unsteadiness have not been detected. 
Properties of palmitoylethanolamide
PEA belongs to the class of N-Acylethanolamides (NAEs) (amides of ethanolamine with long-chain fatty acids) and these are defined as endogenously generated lipid-signaling molecules. These lipids are widely distributed in a variety of plant, invertebrate, and mammalian tissues. They are produced as a biological meaningful answer in inflammation, as a self-regulating servo mechanism. Now we have the possibility to administer PEA as a medical food supplement and regulate the detrimental cascade in sciatic pain.
Bioactive lipids such as PEA, an anandamide analogue, were described for the ﬁrst time in 1957 when it was discovered that PEA, isolated from soybeans, peanuts, and egg yolk, has anti-inﬂammatory properties. 1965, the group of Bachur et al found that these bioactive lipids also existed in mammalian tissues, especially in the brain.
IN 1968 the first paper on PEA is indexed in Pubmed  and since than more than 200 entries can be found! In the 90s the relation between anandamide and PEA was described, and the expression on mastcells of receptors sensitive for those 2 molecules was demonstrated.  In the same period more data supported its neuroprotective effects.  Recent data even show that palmitoylethanolamide can be used in the treatment of atopic dermatitis! 
It was due to the work of professor Rita Levi-Montalcini, Nobel Prize laureat in Medicine 1986, that PEA was taken up in development by the Italian company Lifegroup SpA who developed PEA further in cooperation with professor Montalcini.
Since 2012 a new producer entered the market, the company JP Russell Sciende. They introduced a new product, PeaPure and produced it under strict GMP conditions in the Netherlands for world wide distribution.. The latter compound, PeaPure, is free of sorbitol and excipients and contains pure palmitoylethanolamide only.
Meanwhile it is an established fact that anandamide (AEA) and PEA regulate directly or indirectly many of the same pathophysiological processes, including pain perception, inﬂammation, and neuroprotection. There are a number of biological effects of endocannabinoids which can be enhanced by related endogenous fatty acid derivatives which are devoid of some of these primary effects.
Palmitoylethanolamide is a body-own compound, and a neutraceutical, brought on the market under the names Normas t (classification food for medical purposes) and PeaPure (supplement). PeaPure can be obtained via the internet easily. Always inform your physician wenn using palmitoylethanolamide, to bring him/her up to date.
October 2010, Jan M. Keppel Hesselink, MD, PhD; revision november 2012
 Re G, Barbero R, Miolo A, Di Marzo V. | Palmitoylethanolamide, endocannabinoids and related cannabimimetic compounds in protection against tissue inflammation and pain: potential use in companion animals. | Vet J. | 2007 Jan;173(1):21-30. Epub 2005 Dec 1.
 Baron R, Freynhagen R, Tölle TR, Cloutier C, Leon T, Murphy TK, Phillips K; A0081007 Investigators. | The efficacy and safety of pregabalin in the treatment of neuropathic pain associated with chronic lumbosacral radiculopathy. | Pain. | 2010 Sep;150(3):420-7. Epub 2010 May 20.
 Assini A, Laricchia D, Pizzo R, Pandolfini L, Belletti M, Colucci M, Ratto S. | P1577: The carpal tunnel syndrome in diabetes: clinical and electrophysiological improvement after treatment with palmitoylethanolamide | Eur J Neurol | 2010: 17(S3):295.
 Calabrò RS, Gervasi G, Marino S, Mondo PN, Bramanti P. | Misdiagnosed chronic pelvic pain: pudendal neuralgia responding to a novel use of palmitoylethanolamide. | Pain Med. | 2010 May;11(5):781-4. Epub 2010 Mar 22.
 Petrosino S, Iuvone T, Di Marzo V. | N-palmitoyl-ethanolamine: Biochemistry and new therapeutic opportunities. | Biochimie. | 2010 Jun;92(6):724-7. Epub 2010 Jan 21.
 Phan NQ, Siepmann D, Gralow I, Ständer S. | Adjuvant topical therapy with a cannabinoid receptor agonist in facial postherpetic neuralgia. | J Dtsch Dermatol Ges. | 2010 Feb;8(2):88-91. Epub 2009 Sep 10.
 Benvenuti F, Lattanzi F, De Gori A, Tarli P. | [Activity of some derivatives of palmitoylethanolamide on carragenine-induced edema in the rat paw]. | Boll Soc Ital Biol Sper. | 1968 May 15;44(9):809-13.
 Facci L, Dal Toso R, Romanello S, Buriani A, Skaper SD, Leon A. | Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. | Proc Natl Acad Sci U S A. | 1995 Apr 11;92(8):3376-80.
 Skaper SD, Buriani A, Dal Toso R, Petrelli L, Romanello S, Facci L, Leon A. | The ALIAmide palmitoylethanolamide and cannabinoids, but not anandamide, are protective in a delayed postglutamate paradigm of excitotoxic death in cerebellar granule neurons. | Proc Natl Acad Sci U S A. | 1996 Apr 30;93(9):3984-9.
 Kircik L. | A nonsteroidal lamellar matrix cream containing palmitoylethanolamide for the treatment of atopic dermatitis. | J Drugs Dermatol. | 2010 Apr;9(4):334-8.