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Gliopathic pain

Gliopathic Pain Is A Brand New Term For What We Always Thought To Be Neuropathic Pain. It Refers To Pain Related To Neuropathic Pain, However, The Primary Driver Of This Pain Is Most Probably More Linked To Glia And Asterocytes. The Mechanism Of Gliopathic Pain Is The Hyperactivation Of Glia Cells, Which Results In Neuropathic Pain.

Neuropathic pain: microglia controls neuronal network excitability

Microglia-neuron interactions are leading to altered neural network excitability, the pathogenetic base of neuropathic pain. Modern research demonstrates that one of the key factors driving neurons nuts in neuropathic pain is the inflammatory compound ‘Brain-derived neurotrophic factor (BDNF)’, released by microglia. [1] Microglial BDNF plays a key role in controlling neuronal excitability by causing disinhibition. This […]

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Endocannabinoid, BDNF and inhibition

The neurotrophin brain-derived neurotrophic factor (BDNF) is a potent regulator of inhibitory synaptic transmission, and thus highly important for the central processes related to chronic pain experiences.

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Palmitoylethanolamide, PPAR-alpha and glia

The naturally occurring fatty acid of ethanolamine and palmitic acid, palmitoylethanolamide (PEA), is an important addition to our clinical armamentarium for the treatment of chonic neuropathic pain and related chronic painstates, such as the syndrome of Costen, diabetic and sciatic pain.

PEA is a lipidergic messenger and is known to mimic several endocannabinoid-induced biological responses via novel mechanism of action, without binding to CB1, CB2, and abn-CBD receptors.

During the last decades many imprssive biological actions of PEA have been described, such as influence on immune cells such as inhibition of mast cell degranulation, attenuation of leukocyte extravasation, and modulation of cytokine release from macrophages. have been described. Furthermore PEA acts not only on a variety of peripheral immunocompetent cell types but also seems to inhibit activated microglial cells, and these cells play an important role in both neuropathic pain as well as in secondary neuronal damage.

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Endocannabinoids and palmitoylethanolamide in chronic inflammation

CB2 receptors are mainly expressed by immune cells, where they modulate cytokine release and immune cell migration. Palmitoylethanolamide (PEA is available as a supplement under the brandnames PeaPure and een PEA-houdend product) exerts anti-inflammatory and analgesic actions via several molecular mechanisms, and probably most important is the direct activation of peroxisome proliferator-activated receptor-α (PPAR-α).

In addition to this mechanism of action indirect activation of cannabinoid receptors and of transient receptor potential vanilloid type-1 (TRPV1) channels have been described. Recently the analgesic activity of PEA in animal model of neuropathic pain have been explained not only via indirect activation of the CB1 and TRPV1 receptors but also via the PPAR-γ pathway.

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Palmitoylethanolamide analogue, palmitoylallylamide (L-29) in a pain model

Cannabis and the endogenous cannabinoids are associated with analgesia in acute and chronic pain states. The analgesic effect of the palmitoylethanolamide (PEA) has ben described in many different animal models, and meanhile also in a number of clinical trials. This has prompted to look for analogues of PEA. Palmitoylallylamide (L-29) is such a analogue.

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Palmitoylethanolamide in neuropathic sciatic pain: clinical results


Palmitoylethanolamide (PEA) is an natural and endogenous compound. It is a fatty acid amide and present in many foodstuffs as well as in the human body. In Europe PEA is available as a nutraceutical (dietfood for medical purposes)  in Italy and Spain under the brandname een PEA-houdend product and in the Netherlands and elsewhere as a foodsupplement under the brandname PeaPure. 

PeaPure has the advantage of not containing farmaceutical and chemical excipients, nor sorbitol (as present in een PEA-houdend product and other PEA products).

In 2010 a Spanish publication described clinical meaningful effects of the treatment of lumbosciatic pain with palmitoylethanolamide, PEA. These results were published in Dolor (2010;25:35-42) and were based on a double blind placebo contriolled study.

TWe conducted a furher analysis of the Numbers Needed to Treat we presented at the SIAARTI in 2011 for around 1000 pain specialists, the efficacy of PEA based on the NNT analysis we presented was impressive: 1.5! For details see link.

The presentation at the SIAARTI was moderated and introduced by professor G. Varrassi. 

In various different clinical nerve compression studies, conducted up to 2011, a total of more than 1300 patients  wre treated all confirming positive effects for PEA in sciatic pain (see under)  

PEA is a safe compound, with virtually no side effects, and a robust efficacy (NNT=1.5, see graph: NNT at week 3 for 50% pain reduction on NRS). 


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Palmitoylethanolamide and leucocyte inhibition

Palmitoylethanolamide (PEA) is a lipid amide that occurs in our bodies as well as in many mammalian tissues, and can when administered as a drug, inhibits inflammatory responses via the recent described nuclear receptor, the peroxisome proliferator-activated receptor-alpha (PPAR-alpha).

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Pentoxifylline, tocopherol, and clodronate in radiation-induced lumbosacral polyradiculopathy

Pentoxifylline, tocopherol, and clodronate seem to be effective in radiation-induced lumbosacral polyradiculopathy, as reported by a case study. This is important, although the evidence is weak (case report), as to date there is not one single therapy found to be of use in this late complication of radiation induced polyradiculopathy.

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Metabolism, Mast cells, neuropathic pain and palmitoylethanolamide

mast_cell2.gifInfluencing metabolism is a powerful way to treat various painstates and inflammatory diseases. In chronic painstates metabolic disturbances in tissue and immune cells forms the base of the pathogenesis of neuropathic pain. These metabolic disturbances we can find in glia as well as in neurons and overactive mast cells play a crucial role here. 

Mast cells are found in all human tissues. Their cytoplasm is loaded with granules containing many key mediators of inflammation.Their surface is coated with a great variety of receptors which can trigger exocytosis of the granules. Via this process mast cells influences local tissue metabolism and this leads to inflammation and pathological painstates. Activated mast cells release a whole cascade of potent mediators. Some of these molecules are immediately released, some others later as mast cell metabolism further changes and these cells start synthesizing these second wind mediators via new gene transcriptionprocesses. Modulators of pathological metabolism of mast cells are urgently needed to treat neuropathic pain states, were mast cell activatio play a role. Palmitoylethanolamide is such an endogenious modulator for mast cell metabolism and since 2010 this molecule can be administered as dietfood for medical purposes (brandname een PEA-houdend product®). First we will review briefly some neuropathic pain states and the role of mast cells. Secondly we will review shortly the changed metabolism of mast cells in inflammatory and chronic pain states.

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Mutiple Target Analgesia

In Patent literature sometimes great insights can be found about how to proceed in pain treatment, such as in this patent,  and we enclose here the introductrion and a part of the summary. Pain clearly is especially influenced by non-neuronal cells, is the thesis of this patent.

The current theories and treatment options for persistent pain are not satisfactory. The population of patients with chronic pain and disrupted lives grows constantly. According to the American Pain Foundation, there are 75 million Americans who have chronic pain. Pain is the second most common reason for doctor visits. Unless we can understand how pain is generated, we cannot provide a solution. Our understanding of pain has not advanced since the 1965 publication of the gate theory of pain by Canadian psychologist Ronald Meizack and British physiologist Patrick Wall. In their paper titled “Pain Mechanisms: A New Theory,” Melzack and Wall suggested a gating mechanism within the spinal cord that closed in response to normal stimulation of the fast conducting “touch” nerve fibers; but opened when the slow conducting “pain” fibers transmitted a high volume and intensity of sensory signals. The gate could be closed again if these signals were countered by renewed stimulation of the large fibers.

A recent model, known as Sota Omoigui’s Law, proposes that the origin of all pain is inflammation and the inflammatory response. This model is a dramatic and revolutionary shift from a focus on structural pathology to an understanding of the biochemical origin of Pain.

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Hacking into chronic painstates with the endocannabinoid palmitoylethanolamide

Palmitoylethanolamide (brandnames een PEA-houdend product and PeaPure) is now registered as a supplement in various European countries and is one of the major existing new non-ionchannel tools to target the glia and the neurons in neuropathic and chronic pain. The availability of this compound leads to this discussion on how to influence chronic pain states with this endocannabinoid.

Chronic pain can disrupt brain function and cause many somatic and psychological problems. When neurons fire too much they may change their connections with other neurons and may even die. Crucial to understanding chronic pain are insights in the function of neuronal networks and the role of the all-invading glia cells. But: ‘Glia are nervous system caretakers whose nurturing can go too far. 

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Gliopathic pain, asteropathic pain..


Glia and asterocytes play a central role in neuropathic pain, and gliopathic pain, or asteropathic pain will become new synonyms for neuropathic pain. In a recent hallmark paper the term ‘Gliopathic pain’ was coined.

This is a reason to put our magnifying glass on glia. Gliamodulating drugs will become a new class of neuropathic drugs, the so called gliopathic modulating drugs, and the first prototype, the endogenous fatty acid palmitoylethanolamide, has already been explored in positive proof of principle studies. 

For more than a century doctors are aware of the special properties of glia in response to injury. In Germany in 1894 professor Franz Nissl decribed the reaction of glial cells in relation to the nerve fibers in the spinal cord and highlighted their morphological changes after injury. Microglia becomes mores bigger and more abundant after injury and these glial responses can be seen as a biological reponse to promote nerve repair after injury. However, this response can go biserk and might be one of the most important mechanisms leading to neuropathic pain. 

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Aldskogius H. Mechanisms and consequences of microglial responses to peripheral axotomy. Front Biosci (Schol Ed). 2011 Jun 1;3:857-68.

Antal A, Terney D, Kühnl S, Paulus W. Anodal transcranial direct current stimulation of the motor cortex ameliorates chronic pain and reduces short intracortical inhibition. J Pain Symptom Manage. 2010 May;39(5):890-903. 

De Alba J, Clayton NM, Collins SD, Colthup P, Chessell I, Knowles RG. GW274150, a novel and highly selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), shows analgesic effects in rat models of inflammatory and neuropathic pain. Pain. 2006 Jan;120(1-2):170-81. Epub 2005 Dec 19.

Anonymous. Drug Class Review: Neuropathic Pain: Final Update 1 Report [Internet].

Attal N, Bouhassira D. Chapter 47 Pain in syringomyelia/bulbia. Handb Clin Neurol. 2006;81:705-13. Schurch B, Wichmann W, Rossier AB. Post-traumatic syringomyelia (cystic myelopathy): a prospective study of 449 patients with spinal cord injury. J Neurol Neurosurg Psychiatry. 1996 Jan;60(1):61-7. 

Backonja M, Arndt G, Gombar KA, Check B, Zimmermann M. Response of chronic neuropathic pain syndromes to ketamine: a preliminary study. Pain. 1994 Jan;56(1):51-7.

Barrera-Chacon JM, Mendez-Suarez JL, Jáuregui-Abrisqueta ML, Palazon R, Barbara-Bataller E, García-Obrero I. Oxycodone improves pain control and quality of life in anticonvulsant-pretreated spinal cord-injured patients with neuropathic pain. Spinal Cord. 2011 Jan;49(1):36-42. Epub 2010 Sep 7. 

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. 

Bettoni I, Comelli F, Rossini C, Granucci F, Giagnoni G, Peri F, Costa B. Glial TLR4 receptor as new target to treat neuropathic pain: efficacy of a new receptor antagonist in a model of peripheral nerve injury in mice. Glia. 2008 Sep;56(12):1312-9.

Bishay P, Schmidt H, Marian C, Häussler A, Wijnvoord N, Ziebell S, Metzner J, Koch M, Myrczek T, Bechmann I, Kuner R, Costigan M, Dehghani F, Geisslinger G, Tegeder I. R-flurbiprofen reduces neuropathic pain in rodents by restoring endogenous cannabinoids. PLoS One. 2010 May 13;5(5):e10628.

Broadley KE, Kurowska A, Tookman A. Ketamine injection used orally. Palliat Med. 1996 Jul;10(3):247-50. 

Bulanova E, Bulfone-Paus S. P2 receptor-mediated signaling in mast cell biology. Purinergic Signal. 2010 Mar;6(1):3-17. Epub 2009 Nov 17. 

Calignano A, La Rana G, Piomelli D. Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide. Eur J Pharmacol. 2001 May 11;419(2-3):191-8.

Calignano A, La Rana G, Piomelli D. Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide. Eur J Pharmacol. 2001 May 11;419(2-3):191-8. [116]: Mazzari S, Canella R, Petrelli L, Marcolongo G, Leon A. N-(2-hydroxyethyl)hexadecanamide is orally active in reducing edema formation and inflammatory hyperalgesia by down-modulating mast cell activation. Eur J Pharmacol. 1996 Apr 11;300(3):227-36. 

Chang YW, Waxman SG. Minocycline attenuates mechanical allodynia and central sensitization following peripheral second-degree burn injury. J Pain. 2010 Nov;11(11):1146-54. Epub 2010 Apr 24.

Chen S, Hui H, Zhang D, Xue Y. The combination of morphine and minocycline may be a good treatment for intractable post-herpetic neuralgia. Med Hypotheses. 2010 Dec;75(6):663-5. Epub 2010 Sep 9.

Chiang CY, Li Z, Dostrovsky JO, Sessle BJ. Central sensitization in medullary dorsal horn involves gap junctions and hemichannels. Neuroreport. 2010 Feb 17;21(3):233-7.

Chu YX, Zhang Y, Zhang YQ, Zhao ZQ. Involvement of microglial P2X7 receptors and downstream signaling pathways in long-term potentiation of spinal nociceptive responses. Brain Behav Immun. 2010 Oct;24(7):1176-89. Epub 2010 Jun 8.

Cho Y, Crichlow GV, Vermeire JJ, Leng L, Du X, Hodsdon ME, Bucala R, Cappello M, Gross M, Gaeta F, Johnson K, Lolis EJ. Allosteric inhibition of macrophage migration inhibitory factor revealed by ibudilast. Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11313-8. Epub 2010 Jun 8.

Cohen SP, DeJesus M. Ketamine patient-controlled analgesia for dysesthetic central pain. Spinal Cord. 2004 Jul;42(7):425-8. 

Colburn RW, Rickman AJ, DeLeo JA. The effect of site and type of nerve injury on spinal glial activation and neuropathic pain behavior. Exp Neurol. 1999 Jun;157(2):289-304. [104]: Zhuang ZY, Wen YR, Zhang DR, Borsello T, Bonny C, Strichartz GR, Decosterd I, Ji RR. A peptide c-Jun N-terminal kinase (JNK) inhibitor blocks mechanical allodynia after spinal nerve ligation: respective roles of JNK activation in primary sensory neurons and spinal astrocytes for neuropathic pain development and maintenance. J Neurosci. 2006 Mar 29;26(13):3551-60. 

Cvrcek P. Side effects of ketamine in the long-term treatment of neuropathic pain. Pain Med. 2008 Mar;9(2):253-7. 

Defrin R, Grunhaus L, Zamir D, Zeilig G. The effect of a series of repetitive transcranial magnetic stimulations of the motor cortex on central pain after spinal cord injury. Arch Phys Med Rehabil. 2007 Dec;88(12):1574-80. 

Dworkin RH, O’Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, Kalso EA, Loeser JD, Miaskowski C, Nurmikko TJ, Portenoy RK, Rice AS, Stacey BR, Treede RD, Turk DC, Wallace MS. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007 Dec 5;132(3):237-51. Epub 2007 Oct 24.

Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, Kerns RD, Stucki G, Allen RR, Bellamy N, Carr DB, Chandler J, Cowan P, Dionne R, Galer BS, Hertz S, Jadad AR, Kramer LD, Manning DC, Martin S, McCormick CG, McDermott MP, McGrath P, Quessy S, Rappaport BA, Robbins W, Robinson JP, Rothman M, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Wernicke J, Witter J; IMMPACT. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005 Jan;113(1-2):9-19.

Eijkelkamp N, Heijnen CJ, Willemen HL, Deumens R, Joosten EA, Kleibeuker W, den Hartog IJ, van Velthoven CT, Nijboer C, Nassar MA, Dorn GW 2nd, Wood JN, Kavelaars A. GRK2: a novel cell-specific regulator of severity and duration of inflammatory pain. J Neurosci. 2010 Feb 10;30(6):2138-49.

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. 

Falci SP, Indeck C, Lammertse DP. Posttraumatic spinal cord tethering and syringomyelia: surgical treatment and long-term outcome. J Neurosurg Spine. 2009 Oct;11(4):445-60.

Fattal C, Kong-A-Siou D, Gilbert C, Ventura M, Albert T. What is the efficacy of physical therapeutics for treating neuropathic pain in spinal cord injury patients? Ann Phys Rehabil Med. 2009 Mar;52(2):149-66. Epub 2009 Feb 14. 

Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010 Sep;150(3):573-81. 

Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 2005 Dec 5;118(3):289-305. Epub 2005 Oct 6.

Frech T, Novak K, Revelo MP, Murtaugh M, Markewitz B, Hatton N, Scholand MB, Frech E, Markewitz D, Sawitzke AD. Low-dose naltrexone for pruritus in systemic sclerosis. Int J Rheumatol. 2011;2011:804296. Epub 2011 Sep 12. 

Fregni F, Boggio PS, Lima MC, Ferreira MJ, Wagner T, Rigonatti SP, Castro AW, Souza DR, Riberto M, Freedman SD, Nitsche MA, Pascual-Leone A. A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Pain. 2006 May;122(1-2):197-209. Epub 2006 Mar 27. 

Gao YJ, Ji RR. Chemokines, neuronal-glial interactions, and central processing of neuropathic pain. Pharmacol Ther. 2010 Apr;126(1):56-68. Epub 2010 Feb 1.

Gilron I, Bailey JM, Tu D, Holden RR, Jackson AC, Houlden RL. Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial. Lancet. 2009 Oct 10;374(9697):1252-61. Epub 2009 Sep 30.  

Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med. 2005 Mar 31;352(13):1324-34.

Giner-Pascual M, Alcanyis-Alberola M, Querol F, Salinas-Huertas S, García-Massó X, Gonzalez LM. Transdermal nitroglycerine treatment of shoulder tendinopathies in patients with spinal cord injuries. Spinal Cord. 2011 Sep;49(9):1014-9. doi: 10.1038/sc.2011.41. Epub 2011 May 3. 

Graeber MB. Changing face of microglia. Science. 2010 Nov 5;330(6005):783-8. 

Gautschi OP, Seule MA, Cadosch D, Gores M, Ewelt C, Hildebrandt G, Heilbronner R. Health-related quality of life following spinal cordectomy for syringomyelia. Acta Neurochir (Wien). 2011 Mar;153(3):575-9. Epub 2010 Nov 16. 

Garcia-Ovejero D, Arevalo-Martin A, Petrosino S, Docagne F, Hagen C, Bisogno T, Watanabe M, Guaza C, Di Marzo V, Molina-Holgado E. The endocannabinoid system is modulated in response to spinal cord injury in rats. Neurobiol Dis. 2009 Jan;33(1):57-71. Epub 2008 Sep 30. 

Guasti L, Richardson D, Jhaveri M, Eldeeb K, Barrett D, Elphick MR, Alexander SP, Kendall D, Michael GJ, Chapman V. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain. Mol Pain. 2009 Jul 1;5:35.

Hanna M, O’Brien C, Wilson MC. Prolonged-release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients. Eur J Pain. 2008 Aug;12(6):804-13. Epub 2008 Feb 8.

Hatem SM, Attal N, Ducreux D, Gautron M, Parker F, Plaghki L, Bouhassira D. Clinical, functional and structural determinants of central pain in syringomyelia. Brain. 2010 Nov;133(11):3409-22. Epub 2010 Sep 17.

Heutink M, Post MW, Bongers-Janssen HM, Dijkstra CA, Snoek GJ, Spijkerman DC, Lindeman E. The CONECSI trial: Results of a randomized controlled trial of a multidisciplinary cognitive behavioral program for coping with chronic neuropathic pain after spinal cord injury. Pain. 2011 Nov 17. Epub ahead of print 

Hojomat M, Kleven M, Wala EP. Effects of norketamine enantiomers in rodent models of persistent pain. Pharmacol Biochem Behav. 2008 Oct;90(4):676-85. 

Holtman JR Jr, Crooks PA, Johnson-Hardy JK, Zhou HY, Chen SR, Pan HL. Targeting N-methyl-D-aspartate receptors for treatment of neuropathic pain. Expert Rev Clin Pharmacol. 2011 May 1;4(3):379-388. 

Horvath RJ, Romero-Sandoval EA, De Leo JA. Inhibition of microglial P2X4 receptors attenuates morphine tolerance, Iba1, GFAP and mu opioid receptor protein expression while enhancing perivascular microglial ED2. Pain. 2010 Sep;150(3):401-13. Epub 2010 Jun 22.

Harvey VL, Dickenson AH. Mechanisms of pain in nonmalignant disease. Curr Opin Support Palliat Care. 2008 Jun;2(2):133-9.

Inceoglu B, Jinks SL, Ulu A, Hegedus CM, Georgi K, Schmelzer KR, Wagner K, Jones PD, Morisseau C, Hammock BD. Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways. Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18901-6. Epub 2008 Nov 21.

Inceoglu B, Jinks SL, Schmelzer KR, Waite T, Kim IH, Hammock BD. Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia and mechanical allodynia in a rat model of inflammatory pain. Life Sci. 2006 Nov 10;79(24):2311-9. Epub 2006 Aug 2.

Keppel Hesselink, JM (2011) Syringomyelia in Cavalier spaniels treated succesfully with palmitoylethanolamide https://neuropathie.nu/research-development/syringomyelia-in-cavalier-spaniels-treated-succesfully-with-no.html  

Keppel Hesselink, JM (2011a) https://neuropathie.nu/treatment/palmitoylethanolamide-een PEA-houdend product-information-for-mds.html 

Kiefer RT, Rohr P, Ploppa A, Dieterich HJ, Grothusen J, Koffler S, Altemeyer KH, Unertl K, Schwartzman RJ. Efficacy of ketamine in anesthetic dosage for the treatment of refractory complex regional pain syndrome: an open-label phase II study. Pain Med. 2008 Nov;9(8):1173-201. Epub 2008 Feb 5.

Knowler SP, McFadyen AK, Rusbridge C. Effectiveness of breeding guidelines for reducing the prevalence of syringomyelia. Vet Rec. 2011 Oct 13. [Epub ahead of print] 

Koch M, Kreutz S, Böttger C, Benz A, Maronde E, Ghadban C, Korf HW, Dehghani F. Palmitoylethanolamide protects dentate gyrus granule cells via peroxisome proliferator-activated receptor-alpha. Neurotox Res. 2011 Feb;19(2):330-40. Epub 2010 Mar 11.

Kopsky DJ, Keppel Hesselink JM. Multimodal Stepped Care Approach Involving Topical Analgesics for Severe Intractable Neuropathic Pain in CRPS Type 1: A Case Report. Case Report Med. 2011;2011:319750.

Kopsky DJ, Keppel Hesselink JM. High Doses of Topical Amitriptyline in Neuropathic Pain: Two Cases and Literature Review. Pain Pract. 2011 Jun 16. doi: 10.1111/j.1533-2500.2011.00477.x.  

Kopsky DJ, Keppel Hesselink JM.A new combination cream for the treatment of severe neuropathic pain. J Pain Symptom Manage. 2010 Feb;39(2):e9-e10.  

Kumar K, Taylor RS, Jacques L, Eldabe S, Meglio M, Molet J, Thomson S, O’Callaghan J, Eisenberg E, Milbouw G, Buchser E, Fortini G, Richardson J, North RB. Spinal cord stimulation versus conventional medical management for neuropathic pain: a multicentre randomised controlled trial in patients with failed back surgery syndrome. Pain. 2007 Nov;132(1-2):179-88. Epub 2007 Sep 12. 

Kumru H, Murillo N, Samso JV, Valls-Sole J, Edwards D, Pelayo R, Valero-Cabre A, Tormos JM, Pascual-Leone A. Reduction of spasticity with repetitive transcranial magnetic stimulation in patients with spinal cord injury. Neurorehabil Neural Repair. 2010 Jun;24(5):435-41. Epub 2010 Jan 6. 

LaBuda CJ, Koblish M, Tuthill P, Dolle RE, Little PJ. Antinociceptive activity of the selective iNOS inhibitor AR-C102222 in rodent models of inflammatory, neuropathic and post-operative pain. Eur J Pain. 2006 Aug;10(6):505-12. Epub 2005 Aug 24. [94]: Kim CF, Moalem-Taylor G. Interleukin-17 contributes to neuroinflammation and neuropathic pain following peripheral nerve injury in mice. J Pain. 2011

Lambert DM, Vandevoorde S, Diependaele G, Govaerts SJ, Robert AR. Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice. Epilepsia. 2001 Mar;42(3):321-7.Mar;12(3):370-83.

Lambert DM, Vandevoorde S, Jonsson KO, Fowler CJ. The palmitoylethanolamide family: a new class of anti-inflammatory agents? Curr Med Chem. 2002 Mar;9(6):663-74. 

Leung A, Donohue M, Xu R, Lee R, Lefaucheur JP, Khedr EM, Saitoh Y, André-Obadia N, Rollnik J, Wallace M, Chen R. rTMS for suppressing neuropathic pain: a meta-analysis. J Pain. 2009 Dec;10(12):1205-16. Epub 2009 May 23.

Liebregts, R, Kopsky, D, Keppel Hesselink, JM. Topical Amitriptyline in Post-Traumatic Neuropathic Pain. J Pain Symptom Management Vol. 41, No. 4, April 2011: e6-e8 

Luongo L, Palazzo E, Tambaro S, Giordano C, Gatta L, Scafuro MA, Rossi FS, Lazzari P, Pani L, de Novellis V, Malcangio M, Maione S. 1-(2′,4′-dichlorophenyl)-6-methyl-N-cyclohexylamine-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide, a novel CB2 agonist, alleviates neuropathic pain through functional microglial changes in mice. Neurobiol Dis. 2010 Jan;37(1):177-85. Epub 2009 Oct 3. 

Mao J, Price DD, Hayes RL, Lu J, Mayer DJ, Frenk H.Intrathecal treatment with dextrorphan or ketamine potently reduces pain-related behaviors in a rat model of peripheral mononeuropathy. Brain Res. 1993 Mar 5;605(1):164-8.

Mattioli TA, Milne B, Cahill CM. Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats. Mol Pain. 2010 Apr 16;6:22. 

Mei XP, Zhou Y, Wang W, Tang J, Wang W, Zhang H, Xu LX, Li YQ. Ketamine depresses toll-like receptor 3 signaling in spinal microglia in a rat model of neuropathic pain. Neurosignals. 2011;19(1):44-53. Epub 2011 Mar 9.

van Meeteren ME, Baron W, Beermann C, Dijkstra CD, van Tol EA. Polyunsaturated fatty acid supplementation stimulates differentiation of oligodendroglia cells. Dev Neurosci. 2006;28(3):196-208.

Mercadante S, Lodi F, Sapio M, Calligara M, Serretta R. Long-term ketamine subcutaneous continuous infusion in neuropathic cancer pain. J Pain Symptom Manage. 1995 Oct;10(7):564-8. [39]: Persson J, Hasselström J, Wiklund B, Heller A, Svensson JO, Gustafsson LL. The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans. Acta Anaesthesiol Scand. 1998 Aug;42(7):750-8. 

Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2011 Mar 16;(3):CD007938.

Mori F, Codecà C, Kusayanagi H, Monteleone F, Buttari F, Fiore S, Bernardi G, Koch G, Centonze D. Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis. J Pain. 2010 May;11(5):436-42. Epub 2009 Dec 16. 

Mika J. Modulation of microglia can attenuate neuropathic pain symptoms and enhance morphine effectiveness. Pharmacol Rep. 2008 May-Jun;60(3):297-307.

Noordenbos, Willem. Pain: Problems Pertaining to the Transmission of Nerve Impulses Which Give Rise to Pain. Amsterdam: Elsevier, 1959 

Norrbrink C, Lundeberg T. Acupuncture and massage therapy for neuropathic pain following spinal cord injury: an exploratory study. Acupunct Med. 2011 Jun;29(2):108-15. Epub 2011 Apr 6.   

Nikolajsen L, Hansen PO, Jensen TS. Oral ketamine therapy in the treatment of postamputation stump pain. Acta Anaesthesiol Scand. 1997 Mar;41(3):427-9. [43]: Villanueva-Perez VL, Cerdá-Olmedo G, Samper JM, Mínguez A, Monsalve V, Bayona MJ, De Andrés JA. Oral ketamine for the treatment of type I complex regional pain syndrome. Pain Pract. 2007 Mar;7(1):39-43. 

Ohara PT, Vit JP, Bhargava A, Romero M, Sundberg C, Charles AC, Jasmin L.Gliopathic pain: when satellite glial cells go bad. Neuroscientist. 2009 Oct;15(5):450-63.

Paola FA, Arnold M. Acupuncture and spinal cord medicine. J Spinal Cord Med. 2003 Spring;26(1):12-20. 

Prévinaire JG, Nguyen JP, Perrouin-Verbe B, Fattal C. Chronic neuropathic pain in spinal cord injury: efficiency of deep brain and motor cortex stimulation therapies for neuropathic pain in spinal cord injury patients. Ann Phys Rehabil Med. 2009 Mar;52(2):188-93. Epub 2009 Jan 22.  

Persson J, Axelsson G, Hallin RG, Gustafsson LL. Beneficial effects of ketamine in a chronic pain state with allodynia, possibly due to central sensitization. Pain. 1995 Feb;60(2):217-22.

Persson J, Axelsson G, Hallin RG, Gustafsson LL. Beneficial effects of ketamine in a chronic pain state with allodynia, possibly due to central sensitization. Pain. 1995 Feb;60(2):217-22. [37]: Mathisen LC, Skjelbred P, Skoglund LA, Oye I. Effect of ketamine, an NMDA receptor inhibitor, in acute and chronic orofacial pain. Pain. 1995 May;61(2):215-20.

Roh DH, Yoon SY, Seo HS, Kang SY, Han HJ, Beitz AJ, Lee JH. Intrathecal injection of carbenoxolone, a gap junction decoupler, attenuates the induction of below-level neuropathic pain after spinal cord injury in rats. Exp Neurol. 2010 Jul;224(1):123-32. Epub 2010 Mar 11.

Sabato AF. Idiopathic breakthrough pain: a new hypothesis. Clin Drug Investig. 2010;30 Suppl 2:27-9. doi: 10.2165/1158410-S0-000000000-00000. [99]: O’Callaghan JP, Miller DB. Spinal glia and chronic pain. Metabolism. 2010 Oct;59 Suppl 1:S21-6. [100]: Beggs S, Salter MW. Microglia-neuronal signalling in neuropathic pain hypersensitivity 2.0. Curr Opin Neurobiol. 2010 Aug;20(4):474-80.

Saito O, Svensson CI, Buczynski MW, Wegner K, Hua XY, Codeluppi S, Schaloske RH, Deems RA, Dennis EA, Yaksh TL. Spinal glial TLR4-mediated nociception and production of prostaglandin E(2) and TNF. Br J Pharmacol. 2010 Aug;160(7):1754-64. [81]: Buchanan MM, Hutchinson M, Watkins LR, Yin H. Toll-like receptor 4 in CNS pathologies. J Neurochem. 2010 Jul;114(1):13-27. Epub 2010 Apr 6.

Sampson SM, Kung S, McAlpine DE, Sandroni P. The use of slow-frequency prefrontal repetitive transcranial magnetic stimulation in refractory neuropathic pain. J ECT. 2011 Mar;27(1):33-7. 

Saulino M. Simultaneous treatment of intractable pain and spasticity: observations of combined intrathecal baclofen-morphine therapy over a 10-year clinical experience. Eur J Phys Rehabil Med. 2011 Apr 28. Epub ahead of print 

Staniland AA, Clark AK, Wodarski R, Sasso O, Maione F, D’Acquisto F, Malcangio M. Reduced inflammatory and neuropathic pain and decreased spinal microglial response in fractalkine receptor (CX3CR1) knockout mice. J Neurochem. 2010 Aug;114(4):1143-57. Epub 2010 May 28.

Sweitzer S, De Leo J. Propentofylline: glial modulation, neuroprotection, and alleviation of chronic pain. Handb Exp Pharmacol. 2011;(200):235-50.

Swislocki A, Orth M, Bales M, Weisshaupt J, West C, Edrington J, Cooper B, Saputo L, Islas M, Miaskowski C. A randomized clinical trial of the effectiveness of photon stimulation on pain, sensation, and quality of life in patients with diabetic peripheral neuropathy. J Pain Symptom Manage. 2010 Jan;39(1):88-99. Epub 2009 Nov 5. 

Smith HS, Argoff CE. Pharmacological treatment of diabetic neuropathic pain. Drugs. 2011 Mar 26;71(5):557-89. doi: 10.2165/11588940-000000000-00000.

Tanei T, Kajita Y, Noda H, Takebayashi S, Nakatsubo D, Maesawa S, Wakabayashi T. Efficacy of motor cortex stimulation for intractable central neuropathic pain: comparison of stimulation parameters between post-stroke pain and other central pain. Neurol Med Chir (Tokyo). 2011;51(1):8-14. 

Tanenberg RJ, Irving GA, Risser RC, Ahl J, Robinson MJ, Skljarevski V, Malcolm SK. Duloxetine, pregabalin, and duloxetine plus gabapentin for diabetic peripheral neuropathic pain management in patients with inadequate pain response to gabapentin: an open-label, randomized, noninferiority comparison. Mayo Clin Proc. 2011 Jul;86(7):615-26.

Tronnier V, Baron R, Birklein F, Eckert S, Harke H, Horstkotte D, Hügler P, Hüppe M, Kniesel B, Maier C, Schütze G, Thoma R, Treede RD, Vadokas V; Arbeitsgruppe zur Erstellung der S3-Leitlinie. Epidural spinal cord stimulation for therapy of chronic pain. Summary of the S3 guidelines . Schmerz. 2011 Sep;25(5):484-92. 

Turk DC, Dworkin RH. What should be the core outcomes in chronic pain clinical trials? Arthritis Res Ther. 2004;6(4):151-4. Epub 2004 Jun 4.

Turk DC, Dworkin RH, McDermott MP, Bellamy N, Burke LB, Chandler JM, Cleeland CS, Cowan P, Dimitrova R, Farrar JT, Hertz S, Heyse JF, Iyengar S, Jadad AR, Jay GW, Jermano JA, Katz NP, Manning DC, Martin S, Max MB, McGrath P, McQuay HJ, Quessy S, Rappaport BA, Revicki DA, Rothman M, Stauffer JW, Svensson O, White RE, Witter J. Analyzing multiple endpoints in clinical trials of pain treatments: IMMPACT recommendations. Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. Pain. 2008 Oct 31;139(3):485-93. Epub 2008 Aug 15.

Walker JM, Krey JF, Chu CJ, Huang SM. Endocannabinoids and related fatty acid derivatives in pain modulation. Chem Phys Lipids. 2002 Dec 31;121(1-2):159-72. 

Wang KC, Wang SJ, Fan LW, Cai Z, Rhodes PG, Tien LT. Interleukin-1 receptor antagonist ameliorates neonatal lipopolysaccharide-induced long-lasting hyperalgesia in the adult rats. Toxicology. 2011 Jan 11;279(1-3):123-9. Epub 2010 Oct 19. [79]: Kim CF, Moalem-Taylor G. Interleukin-17 contributes to neuroinflammation and neuropathic pain following peripheral nerve injury in mice. J Pain. 2011 Mar;12(3):370-83.

Watkins LR, Hutchinson MR, Rice KC, Maier SF. The "toll" of opioid-induced glial activation: improving the clinical efficacy of opioids by targeting glia. Trends Pharmacol Sci. 2009 Nov;30(11):581-91. Epub 2009 Sep 15.

Wiffen PJ, McQuay HJ, Edwards JE, Moore RA. Gabapentin for acute and chronic pain. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD005452. Heutink M, Post MW, Wollaars MM, van Asbeck FW. Chronic spinal cord injury pain: pharmacological and non-pharmacological treatments and treatment effectiveness. Disabil Rehabil. 2011;33(5):433-40. Epub 2010 Aug 9.

Wiffen PJ, Derry S, Moore RA, McQuay HJ. Carbamazepine for acute and chronic pain in adults. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD005451. Drug Class Review: Neuropathic Pain: Final Update 1 Report [Internet]. Chogtu B, Bairy KL, Smitha D, Dhar S, Himabindu P. | Comparison of the efficacy of carbamazepine, gabapentin and lamotrigine for neuropathic pain in rats. Indian J Pharmacol.2011 Sep;43(5):596-8.

Wiffen PJ, Derry S, Moore RA. Lamotrigine for acute and chronic pain. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD006044.

Williams KA, Gonzalez-Fernandez M, Hamzehzadeh S, Wilkinson I, Erdek MA, Plunkett A, Griffith S, Crooks M, Larkin T, Cohen SP. A multi-center analysis evaluating factors associated with spinal cord stimulation outcome in chronic pain patients. Pain Med. 2011 Aug;12(8):1142-53. doi: 10.1111/j.1526-4637.2011.01184.x. Epub 2011 Jul 12. 

Wu A, Green CR, Rupenthal ID, Moalem-Taylor G. Role of gap junctions in chronic pain. J Neurosci Res. 2011 Oct 4. doi: 10.1002/jnr.22764. Epub ahead of print 

Rahn EJ, Hohmann AG. Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside. Neurotherapeutics. 2009 Oct;6(4):713-37.

Rivers JR, Ashton JC. The development of cannabinoid CBII receptor agonists for the treatment of central neuropathies. Cent Nerv Syst Agents Med Chem. 2010 Mar;10(1):47-64.

Teasell RW, Mehta S, Aubut JA, Foulon B, Wolfe DL, Hsieh JT, Townson AF, Short C; Spinal Cord Injury Rehabilitation Evidence Research Team. A systematic review of pharmacologic treatments of pain after spinal cord injury. | Arch Phys Med Rehabil. 2010 May;91(5):816-31.

Saadé NE, Jabbur SJ. Nociceptive behavior in animal models for peripheral neuropathy: spinal and supraspinal mechanisms. Prog Neurobiol. 2008 Sep;86(1):22-47. Epub 2008 Jun 18.

Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci. 2007 Nov;10(11):1361-8. [102]: Garrison CJ, Dougherty PM, Kajander KC, Carlton SM. Staining of glial fibrillary acidic protein (GFAP) in lumbar spinal cord increases following a sciatic nerve constriction injury. Brain Res. 1991 Nov 22;565(1):1-7. 

Sweitzer SM, Colburn RW, Rutkowski M, DeLeo JA. Acute peripheral inflammation induces moderate glial activation and spinal IL-1beta expression that correlates with pain behavior in the rat. Brain Res. 1999 May 22;829(1-2):209-21.

Sigtermans MJ, van Hilten JJ, Bauer MC, Arbous MS, Marinus J, Sarton EY, Dahan A. Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1. Pain. 2009 Oct;145(3):304-11. Epub 2009 Jul 14.

Stemler I. Advocating for the traumatically brain injured child. Chart. 1992 Oct;89(8):6.

Xu B, Zhang WS, Yang JL, Lû N, Deng XM, Xu H, Zhang YQ. Evidence for suppression of spinal glial activation by dexmedetomidine in a rat model of monoarthritis. Clin Exp Pharmacol Physiol. 2010 Oct;37(10):e158-66. doi: 10.1111/j.1440-1681.2010.05426.x.

 Yanagihara Y, Ohtani M, Kariya S, Uchino K, Hiraishi T, Ashizawa N, Aoyama T, Yamamura Y, Yamada Y, Iga T. Plasma concentration profiles of ketamine and norketamine after administration of various ketamine preparations to healthy Japanese volunteers. Biopharm Drug Dispos. 2003 Jan;24(1):37-43. 

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Gliopathic pain in orofacial pain

Chiang CY, Dostrovsky JO, and colleagues from the Department of Oral Physiology, Faculty of Dentistry, University of Toronto, Canada, adress the role of glia in orofacial pain in the Neuroscientist of June 2011.

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Opioids activate Glia: counterproductive in neuropathic pain…

Opioids can cause chronic pain, especially neuropathic pain, were glia and asterocytes are happy to become over activated.  After chronic opiate exposure, this excitatory effect emerges contributing to analgesic tolerance and opioid-induced hyperalgesia, and the glia are key in this negative pain cascade.

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Ketamin might have glia as target for neuropathic pain

Glia is a new target in the treatment of neuropathic pain. Ketamine might have a mode of action related to glia hyperactivity.

The acute analgesic effects of ketamine are generally believed to be mediated by the inhibition of NMDA receptors in nociceptive neurons. The authors explored the possible effect of ketamine on spinal microglia. They found that  S-ketamine preferentially suppressed the nerve injury-induced development of tactile allodynia and hyperactivation of spinal microglia.

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Neuron-glia crosstalk gets serious: role in pain hypersensitivity

glia_jmkh.gifThis titel of a recent article demonstrates the increasing awareness in the scientific community about the relevence of the once seen as unimportant glia cells and the nervous tissue.  Glia and asterocytes play a very important role in the genesis of neuropathic pain. The word gliopathic pain is recently coined to capture this importance…A low-grade inflammation in the spinal cord and along the pain pathways to thalamus and the parietal cortex is the hallmark of chronic pain states and glia plays the key role!

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Bladder pain syndrome (BPS) and glia cells

The urothelium, the epithelial lining of the lower urinary tract (LUT), most probably plays an important role in bladder function due to its intercations with bladder nerves, smooth muscle, and cells of the immune systems.

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Glia modulator propentofyllin not active on human non-neuronal cells

Glial cells are involved in neuropathic pain conditions. Several glial-targeted agents are in development for the treatment of pain conditions. The glial modulating agent, propentofylline, did however not decrease pain reported in association with post-herpetic neuralgia. Why? Because the human non-neuronal cells do not listen to this glia modulator, although rat non neuronal cells do….

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Glia as target for new analgesics and palmitoylethanolamide: PEA in sciatic pain

In 2011 our institute was present at the SIAARTI, in Perugia, Italie, at the biggest Italian congres for anesthesiologists and pain specialists (SIAARTI, Società Italiana di Anestesia, Analgesia, Rianimazione e Terapia Intensiva). siaarti_2011_sciatic_pain_.png
At this congress we had the honor and pleasure to talk extensively on the efficacy of palmitoylethanolamide (PEA) and present for the first time our analysis of the efficacy and safety of this compound related to its Numbers Needed to Treat, based on a RCT with 636 patients.

We will discuss the results of this analysis based on the presentation at the SIAARTI.The entire presentation under the link, start at 1 minute 53 to skipp the Italian introduction.

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Glia modulators for neuropathic pain

Since 1994 when Meller and colleagues for the first time demonstrated that by inhibiting astrocyte functions, neuropathic pain did not emerge, many glia modulators have been explored as new inroads in the treatment of neuropathic pain. Some specifically inhibit cytokines (like Il-18), others enhance anti-inflammatory cytokines, such as Il-10, and again others stabilize mastcell degranulation and are PARR agonists, such as palmitoylethanolamide. Here a summary:

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New Targets in pain, non-neuronal cells, and the role of palmitoylethanolamide: A Prezi!

Here, in this flshing Prezi, we will review some of the recent evidence to support non-neuronal cells as new targets for the treatment of neuropathic pain. As clinical proof of concept we will discuss the efficacy and safety of the endogenous molecule palmitoylethanolamide (PEA) in the treatment of various neuropathic painstates.

PEA is available as food for medical purposeunder the name Peavera and een PEA-houdend product and as a foodsupplement under the name PeaPure.

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Propentofylline, a glia modulator

Glia modulators are the new kids on the block for the treatment of intractable neuropathic pain. Gliopathic pain is perhaps a better term for this pain, as the winding up phenomena is very much driven by activated glia. The search for glia modulators therefore is quite exciting. We work in our clinic with a number of glia modulators in treatment refractory neuropathic pain and sometimes with amazing results. 

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Toll receptor 4 and glia in neuropathic pain

Toll-like receptor 4 (TLR4) expressed on spinal microglia and astrocytes and seems to play an important role in the regulation of pain signalling in neuropathic pain. Moreover, compounds like Trental (pentoxifylline) and low dose naltrexone are interesting instruments to modulate the Toll 4 receptor and perhaps these compounds will even help in the treatment of intractable neuropathic pain.

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New insights in mast cell modulation by palmitoylethanolamide

New Insights in Mast Cell Modulation by Palmitoylethanolamide

was the title of a review of drs De Filippis, Iuvone and collaegues in CNS & Neurological Disorders – Drug Targets, 2013, 12, 78-83. 

The authors discussed the findings of Levi-Montalcini and the mechanism proposed by her group to explain PEA action, first identified in the 1990s,  the so called ALIA mechanismor the ““Autacoid LocalInflammation Antagonism””. They pointed out that later this terminology was modified into ““Autacoid Local Injury Antagonism””.
The change in acronym was based on the observation that ““the pharmacological effects of PEA appear to reflect the consequences of supplying the tissue with a sufficient quantity of its physiological regulators of cellular homeostasis”” (Aloe, L.; Leon, A.; Levi-Montalcini, R. A proposed autacoids mechanism controlling mastocyte behavior. Agents Actions 1993; 39: C145-7). Thus, De Fillipis et al point out that
PEA needs to be being viewed as a broad bioactive ““protector”” instead of limiting its field of action to the inflammation response.

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Neuroinflammation explains aspects of chronic pain: what about naltrexone?

‘Neuroinflammation explains aspects of chronic pain and opens new avenues for therapeutic interventions’ is the titel of an editorial of Harald Breivik and Torsten Gordh, in the Scandinavian Journal of Pain, Volume 1, Issue 2, April 2010, Pages 65-66. These editors raise important issues, as current drugs for chronic pain exclusively target neuronal mechanisms, and these drugs appear only partly effective. Therefore, new treatment strategies via the manipulation of the neuron–glia interactions in pain may lead to new break through approaches. It seems that more than one basic neuroscientist claims that inhibition of immune function might become a major avenue for treating neuropathic pain in the future.

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Wise reactions of glia in neuropathic pain possible

Gia cells play an important role in neuropathic pain. So important that some scientists prefer to speak about gliopathic pain in stead of neuropathic pain. These cells produce their own modulators we could even say, their own endogeneous ‘painkillers’. These modulators play an important role in decreasing winding up mechanisms in neuropathic pain. Anandamide (arachidonoylethanolamide, AEA) and its sistermolecule palmitoylethanolamide (PEA, een PEA-houdend product), both are such modulators, and these molecules have positive influences  in neuropathic pain and inflammation related to neuropathic pain. Both molecules are classical autocoids, and they fulfill the three criteria required for autocoids of lipid transmitters:

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Proinflammatory cytokines in small fiber neuropathy

Proinflammatory cytokines in small fiber neuropathy can be found in the skin of patients suffering from Small fiber neuropathy (SFN). SNF is a sensory neuropathy with neuropathic pain in feet and hands, and normal findings in routine EMG/nerve conduction studies. These results make patients very uneasy, as they tend to believe their pain is between the ears. Now new findings show a crisp pathological disturbance in the skin of the affected area. SFN is as many other neuropathic pain states a chronic inflammation.

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Adelmidrol: a novel glia modulator

adelmidrol.gifAdelmidrol is a novel chemical synthetized non-natural compound, and resembles in its biological effects palitoylethanolamide (PEA). PEA however is a natural molecule, adelmidrol as said is synthetical and cannot be found in living organisms. The father of this molecule is the Italian chemist  Dr Francesco della Valle, pupil of professor Rita Levi-Montalchini, the Nobel laureate, praised due to her work on nerve growth factors (Died on December 2012, 103 years old). They started working on the group of Aliamides around 1990, and in 1993 Professor Montalcini published the first paper on the role of PEA as a mastcell modulator. The adelmidrol chapter adds to the importance of these molecules as biological modulators.

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Neuropathic pain, glia and cannabis

Despite the frequency of diabetes mellitus and its relationship to diabetic peripheral neuropathy (DPN) and neuropathic pain (NeP), our understanding of underlying mechanisms leading to chronic pain in diabetes remains poor. Recent evidence has demonstated a prominent role of microglial cells in neuropathic pain states. One potential therapeutic option gaining clinical acceptance is the cannabinoids, for which cannabinoid receptors (CB) are expressed on neurons and microglia. These are the opening words of a brand new article on ‘Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain’ from the hand of Cory C Toth and colleagues. 

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