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

Overview

Journal CNS Neurol Disord Drug Targets

Publisher Bentham Science Publishers

Specialties Neurology
Pharmacology

Date 2019 Jul 5

PMID 31269891

Citations 10

Authors

Giorgio Cruccu

Giulia Di Stefano

Paolo Marchettini

Andrea Truini

Affiliations

Soon will be listed here.

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.

Citing Articles

Extended Treatment with Micron-Size Oral Palmitoylethanolamide (PEA) in Chronic Pain: A Systematic Review and Meta-Analysis.

Schweiger V, Schievano C, Martini A, Polati L, Del Balzo G, Simari S Nutrients. 2024; 16(11).

PMID: 38892586 PMC: 11174044. DOI: 10.3390/nu16111653.

Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain Related to Chronic Inflammatory Demyelinating Polyneuropathy: A Proof-of-Concept Study.

Cocito D, Peci E, Torrieri M, Clerico M J Clin Med. 2024; 13(10).

PMID: 38792328 PMC: 11122609. DOI: 10.3390/jcm13102787.

Ultramicronized -palmitoylethanolamine Contributes to Morphine Efficacy Against Neuropathic Pain: Implication of Mast Cells and Glia.

Micheli L, Lucarini E, Nobili S, Bartolucci G, Pallecchi M, Toti A Curr Neuropharmacol. 2022; 22(1):88-106.

PMID: 36443965 PMC: 10716887. DOI: 10.2174/1570159X21666221128091453.

Managing Chronic Neuropathic Pain: Recent Advances and New Challenges.

Hange N, Poudel S, Ozair S, Paul T, Nambakkam M, Shrestha R Neurol Res Int. 2022; 2022:8336561.

PMID: 36277331 PMC: 9581623. DOI: 10.1155/2022/8336561.

Effects of Palmitoylethanolamide (PEA) on Nociceptive, Musculoskeletal and Neuropathic Pain: Systematic Review and Meta-Analysis of Clinical Evidence.

Scuteri D, Guida F, Boccella S, Palazzo E, Maione S, Rodriguez-Landa J Pharmaceutics. 2022; 14(8).

PMID: 36015298 PMC: 9414729. DOI: 10.3390/pharmaceutics14081672.

References

Skljarevski V, Zhang S, Desaiah D, Alaka K, Palacios S, Miazgowski T . 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. DOI: 10.1016/j.jpain.2010.03.002. View

Dominguez C, Martin A, Ferrer F, Puertas M, Muro A, Gonzalez J . N-palmitoylethanolamide in the treatment of neuropathic pain associated with lumbosciatica. Pain Manag. 2014; 2(2):119-24. DOI: 10.2217/pmt.12.5. View

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; 2017:1486010. PMC: 5569747. DOI: 10.1155/2017/1486010. View

Skaper S . Mast Cell - Glia Dialogue in Chronic Pain and Neuropathic Pain: Blood-Brain Barrier Implications. CNS Neurol Disord Drug Targets. 2016; 15(9):1072-1078. DOI: 10.2174/1871527315666160829105533. View

Qaseem A, Wilt T, McLean R, Forciea M, Denberg T, Barry M . 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):514-530. DOI: 10.7326/M16-2367. View

Luongo L, Guida F, Boccella S, Bellini G, Gatta L, Rossi F . 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. DOI: 10.2174/1871527311312010009. View

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):541-550. DOI: 10.1016/j.pain.2008.06.003. View

Juanola Roura X, Estevez E, Leon Vazquez F, Villamor A, Garcia Yebenes M, Silva R . Reccomendations for the detection, study and referral of inflammatory low-back pain in primary care. Reumatol Clin. 2014; 11(2):90-8. DOI: 10.1016/j.reuma.2014.04.007. View

Chirchiglia D, Chirchiglia P, Signorelli F . Nonsurgical lumbar radiculopathies treated with ultramicronized palmitoylethanolamide (umPEA): A series of 100 cases. Neurol Neurochir Pol. 2017; 52(1):44-47. DOI: 10.1016/j.pjnns.2017.11.002. View

10.

van Tulder M, Koes B, Bombardier C . Low back pain. Best Pract Res Clin Rheumatol. 2002; 16(5):761-75. DOI: 10.1053/berh.2002.0267. View

11.

Cruccu G, Di Stefano G, Fattapposta F, Jann S, Padua L, Schenone A . L-Acetyl-carnitine in Patients with Carpal Tunnel Syndrome: Effects on Nerve Protection, Hand Function and Pain. CNS Drugs. 2017; 31(12):1103-1111. PMC: 5747578. DOI: 10.1007/s40263-017-0476-2. View

12.

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. DOI: 10.2174/1871527311312010008. View

13.

Evangelista M, Cilli , De Vitis R, Militerno A, Fanfani F . Ultra-micronized 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):291-298. DOI: 10.2174/1871527317666180420143830. View

14.

Artukoglu B, Beyer C, Zuloff-Shani A, Brener E, Bloch M . Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis. Pain Physician. 2017; 20(5):353-362. View

15.

Hoy D, March L, Brooks P, Blyth F, Woolf A, Bain C . The global burden of low back pain: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis. 2014; 73(6):968-74. DOI: 10.1136/annrheumdis-2013-204428. View

16.

Fischer B . GABA Receptors as Targets for the Management of Pain-related Disorders: Historical Perspective and Update. CNS Neurol Disord Drug Targets. 2017; 16(6):658-663. DOI: 10.2174/1871527316666170207155149. View

17.

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. 2016; 174(11):1349-1365. PMC: 5429331. DOI: 10.1111/bph.13580. View

18.

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. View

19.

Islam N, Abbas M, Rahman S . Neuropathic Pain and Lung Delivery of Nanoparticulate Drugs: An Emerging Novel Therapeutic Strategy. CNS Neurol Disord Drug Targets. 2016; 16(3):303-310. DOI: 10.2174/1871527315666161213104417. View

20.

Haanpaa M, Attal N, Backonja M, Baron R, Bennett M, Bouhassira D . NeuPSIG guidelines on neuropathic pain assessment. Pain. 2010; 152(1):14-27. DOI: 10.1016/j.pain.2010.07.031. View