Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Clinical Trial

Micronized Palmitoylethanolamide: A Post Hoc Analysis of a Controlled Study in Patients with Low Back Pain – Sciatica

Author(s): Giorgio Cruccu*, Giulia Di Stefano, Paolo Marchettini and Andrea Truini

Volume 18, Issue 6, 2019

Page: [491 - 495] Pages: 5

DOI: 10.2174/1871527318666190703110036

open access plus

Abstract

Background: Despite being widely prescribed, relatively few controlled trials have been conducted on the class of neurotrophic/antinociceptive nutraceuticals. While performing a search in the literature, we came across an old registration study on micronized palmitoylethanolamide in patients with low back pain – sciatica by Guida and colleagues.

Methods: We contacted the authors of the article and obtained all the original material, which allowed us to reanalyze the study. We assessed its clinical relevance by calculating the numbers needed to treat for pain (visual analog scale) and function (Roland-Morris Questionnaire). After excluding patients for whom the information available was insufficient, we assigned each patient to one of the five categories of increasing probability of neuropathic pain: pure lumbago, lumbago with projecting pain to surrounding regions (e.g. gluteus or groin), lumbago with projecting pain to the thigh or leg, pure sciatica and radiculopathy, and investigated any correlations (Spearman) between the improvement in pain and function with these five classes.

Results: Compared with placebo, palmitoylethanolamide 600 mg/die yielded a number needed to treat of 1.7 (95% confidence interval: 1.4-2) for pain, and 1.5 (95% confidence interval: 1.4-1.7) for function. The correlation between the five categories was highly significant for pain relief (P <0.0001), though not significant for reduced dysfunction.

Conclusion: Palmitoylethanolamide was extremely effective on pain and function in a large cohort of patients with low back pain – sciatica. Although, the multiple mechanisms of action of palmitoylethanolamide are ideal for mixed pain conditions such as low back pain – sciatica, the correlation between pain relief and the likelihood of neuropathic pain suggests that this drug exerts a predominant action on the neuropathic pain component.

Keywords: Micronized palmitoylethanolamide, low back pain, neuropathic pain, mixed pain, nutraceuticals, NSAIDs, placebo.

Graphical Abstract
[1]
Papanas N, Ziegler D. Efficacy of α-lipoic acid in diabetic neuropathy. Expert Opin Pharmacother 2014; 15(18): 2721-31.
[2]
Skaper SD, Facci L, Fusco M, et al. Palmitoylethanolamide, a naturally occurring disease-modifying agent in neuropathic pain. Inflammopharmacology 2014; 22(2): 79-94. [http://dx.doi.org/10.1007/s10787-013-0191-7]. [PMID: 24178954].
[3]
Javed S, Petropoulos IN, Alam U, Malik RA. Treatment of painful diabetic neuropathy. Ther Adv Chronic Dis 2015; 6(1): 15-28.
[4]
Li S, Li Q, Li Y, Li L, Tian H, Sun X. Acetyl-L-carnitine in the treatment of peripheral neuropathic pain: A systematic review and meta-analysis of randomized controlled trials. PLoS One 2015; 10(3)e0119479
[5]
Cruccu G, Di Stefano G, Fattapposta F, et al. L-acetyl-carnitine in patients with carpal tunnel syndrome: Effects on nerve protection, hand function and pain. CNS Drugs 2017; 31(12): 1103-11.
[6]
Paladini A, Fusco M, Cenacchi T, Schievano C, Piroli A, Varrassi G. Palmitoylethanolamide, a special food for medical purposes, in the treatment of chronic pain: A pooled data meta-analysis. Pain Physician 2016; 19(2): 11-24.
[7]
Artukoglu BB, Beyer C, Zuloff-Shani A, Brener E, Bloch MH. Efficacy of palmitoylethanolamide for pain: A meta-analysis. Pain Physician 2017; 20(5): 353-62.
[8]
Hoy D, March L, Brooks P, et al. The global burden of low back pain: Estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014; 73(6): 968-74.
[9]
Foster NE, Anema JR, Cherkin D, et al. Prevention and treatment of low back pain: Evidence, challenges, and promising directions. Lancet 2018; 391(10137): 2368-83.
[10]
van Tulder M, Koes B, Bombardier C. Low back pain. Best Pract Res Clin Rheumatol 2002; 16(5): 761-75.
[11]
Mathieson S, Kasch R, Maher CG, et al. Combination drug therapy for the management of low back pain and sciatica: Systematic Review and meta-analysis. J Pain 2019; 20(1): 1-15.
[12]
Schreijenberg M, Koes BW, Lin CC. Guideline recommendations on the pharmacological management of non-specific low back pain in primary care - is there a need to change? Expert Rev Clin Pharmacol 2019; 12(2): 145-57.
[13]
Guida G, de Martino M, de Fabiani A, et al. Palmitoylethanolamide (Normast) in chronic neuropathic pain caused by compressive-type lumbar sciatica: A multicenter clinical trial. DOLOR 2010; 25: 35-42.
[14]
Baron R, Binder A. How neuropathic is sciatica? The mixed pain concept. Orthopade 2004; 33(5): 568-75.
[15]
Freynhagen R, Baron R. The evaluation of neuropathic components in low back pain. Curr Pain Headache Rep 2009; 13(3): 185-90.
[16]
Roland M, Fairbank J. The roland-morris disability questionnaire and the oswestry disability questionnaire. Spine 2000; 25(24): 3115-24.
[17]
Chatellier G, Zapletal E, Lemaitre D, Menard J, Degoulet P. The number needed to treat: A clinically useful nomogram in its proper context. BMJ 1996; 312(7028): 426-9.
[18]
Freynhagen R, Arevalo Parada H, Calderon-Ospina CA, et al. Current understanding of the mixed pain concept: A brief narrative review. Curr Med Res Opin 2018; 1-16.
[19]
Petrosino S, Di Marzo V. The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. Br J Pharmacol 2017; 174(11): 1349-65.
[20]
Alhouayek M, Muccioli GG. Harnessing the anti-inflammatory potential of palmitoylethanolamide. Drug Discov Today 2014; 19(10): 1632-9.
[21]
Brotini S, Schievano C, Guidi L. Ultra-micronized palmitoylethanolamide: An efficacious adjuvant therapy for Parkinson’s disease. CNS Neurol Disord Drug Targets 2017; 16(6): 705-13.
[22]
Zhao H, Alam A, Chen Q, et al. The role of microglia in the pathobiology of neuropathic pain development: What do we know? Br J Anaesth 2017; 118(4): 504-16.
[23]
Skaper SD, Facci L, Zusso M, Giusti P. An inflammation-centric view of neurological disease: Beyond the neuron. Front Cell Neurosci 2018; 12: 72.
[24]
Skaper SD. Mast cell - glia dialogue in chronic pain and neuropathic pain: Blood-brain barrier implications. CNS Neurol Disord Drug Targets 2016; 15(9): 1072-8.
[25]
Luongo L, Guida F, Boccella S, et al. Palmitoylethanolamide reduces formalin-induced neuropathic-like behaviour through spinal glial/microglial phenotypical changes in mice. CNS Neurol Disord Drug Targets 2013; 12(1): 45-54.
[26]
Bettoni I, Comelli F, Colombo A, Bonfanti P, Costa B. Non-neuronal cell modulation relieves neuropathic pain: Efficacy of the endogenous lipid palmitoylethanolamide. CNS Neurol Disord Drug Targets 2013; 12(1): 34-44.
[27]
Evangelista M, Cilli V, De Vitis R, Militerno A, Fanfani F. Ultramicronized palmitoylethanolamide effects on sleep-wake rhythm and neuropathic pain phenotypes in patients with carpal tunnel syndrome: An open-label, randomized controlled study. CNS Neurol Disord Drug Targets 2018; 17(4): 291-8.
[28]
Haanpää M, Attal N, Backonja M, et al. NeuPSIG guidelines on neuropathic pain assessment. Pain 2011; 152(1): 14-27.
[29]
Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis. Lancet Neurol 2015; 14(2): 162-73.
[30]
Skljarevski V, Zhang S, Desaiah D, et al. Duloxetine versus placebo in patients with chronic low back pain: A 12-week, fixed-dose, randomized, double-blind trial. J Pain 2010; 11(12): 1282-90.
[31]
Qaseem A, Wilt TJ, McLean RM, Forciea MA. Noninvasive treatments for acute, subacute, and chronic low back pain: A clinical practice guideline from the american college of physicians. Ann Intern Med 2017; 166(7): 514-30.
[32]
Juanola Roura X, Collantes Estévez E, León Vázquez F, et al. Reccomendations for the detection, study and referral of inflammatory low-back pain in primary care. Reumatol Clin 2015; 11(2): 90-8.
[33]
Fischer BD. GABA<sub>A</sub> Receptors as targets for the management of pain-related disorders: Historical perspective and update. CNS Neurol Disord Drug Targets 2017; 16(6): 658-63.
[34]
Islam N, Abbas M, Rahman S. Neuropathic pain and lung delivery of nanoparticulate drugs: An emerging novel therapeutic strategy. CNS Neurol Disord Drug Targets 2017; 16(3): 303-10.
[35]
Nestmann ER. Safety of micronized palmitoylethanolamide (microPEA): lack of toxicity and genotoxic potential. Food Sci Nutr 2016; 5(2): 292-309.
[36]
Higgins JPT, Green S, Eds. Cochrane handbook for systematic reviews of interventions version 510 The Cochrane Collaboration 2011. Updated March . 2011.
[37]
Henschke N, Maher CG, Refshauge KM, et al. Characteristics of patients with acute low back pain presenting to primary care in Australia. Clin J Pain 2009; 25(1): 5-11.
[38]
Weber H, Holme I, Amlie E. The natural course of acute sciatica with nerve root symptoms in a double-blind placebo-controlled trial evaluating the effect of piroxicam. Spine 1993; 18(11): 1433-8.
[39]
Costa B, Comelli F, Bettoni I, Colleoni M, Giagnoni G. The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB(1), TRPV1 and PPARgamma receptors and neurotrophic factors. Pain 2008; 139(3): 541-50.
[40]
Di Cesare Mannelli L, D’Agostino G, Pacini A, et al. Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy: Pain relief and neuroprotection share a PPAR-alpha-mediated mechanism. Mediators Inflamm 2013; 2013328797
[41]
Seol TK, Lee W, Park S, et al. Effect of palmitoylethanolamide on inflammatory and neuropathic pain in rats. Korean J Anesthesiol 2017; 70(5): 561-6.
[42]
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; 11(5): 781-4.
[43]
Truini A, Biasiotta A, Di Stefano G, et al. Palmitoylethanolamide restores myelinated-fibre function in patients with chemotherapy-induced painful neuropathy. CNS Neurol Disord Drug Targets 2011; 10(8): 916-20.
[44]
Schifilliti C, Cucinotta L, Fedele V, Ingegnosi C, Luca S, Leotta C. Micronized palmitoylethanolamide reduces the symptoms of neuropathic pain in diabetic patients. Pain Res Treat 2014; 2014849623
[45]
Domínguez CM, Martín AD, Ferrer FG, et al. N-palmitoyl-ethanolamide in the treatment of neuropathic pain associated with lumbosciatica. Pain Manag 2012; 2(2): 119-24.
[46]
Cocito D, Peci E, Ciaramitaro P, Merola A, Lopiano L, Lopiano L. Short-term efficacy of ultramicronized palmitoylethanolamide in peripheral neuropathic pain. Pain Res Treat 2014; 2014854560
[47]
Del Giorno R, Skaper S, Paladini A, Varrassi G, Coaccioli S. Palmitoylethanolamide in fibromyalgia: Results from prospective and retrospective observational studies. Pain Ther 2015; 4(2): 169-78.
[48]
Chirchiglia D, Chirchiglia P, Signorelli F. Nonsurgical lumbar radiculopathies treated with ultramicronized palmitoylethanolamide (umPEA): A series of 100 cases. Neurol Neurochir Pol 2018; 52(1): 44-7.
[49]
Paladini A, Varrassi G, Bentivegna G, Carletti S, Piroli A, Coaccioli S. Palmitoylethanolamide in the treatment of failed back surgery syndrome. Pain Res Treat 2017; 20171486010

© 2024 Bentham Science Publishers | Privacy Policy