title: Palmitoylethanolamide, a Special Food for Medical Purposes, in the Treatment of Chronic Pain: A Pooled Data Meta-analysis.
abstract: BACKGROUND
  A growing body of evidence suggests that neuroinflammation, which is characterized by infiltration of immune cells, activation of mast cells and glial cells, and production of inflammatory mediators in the peripheral and central nervous systems, has an important role in the induction and maintenance of chronic pain. These findings support the notion that new therapeutic opportunities for chronic pain might be based on anti-inflammatory and pro-resolving mediators that act on immune cells, in particular mast cells and glia, to mitigate or abolish neuroinflammation. Among anti-inflammatory and pro-resolving lipid mediators, palmitoylethanolamide (PEA) has been reported to down-modulate mast cell activation and to control glial cell behaviors.
  
  
  OBJECTIVE
  The aim of this study was to perform a pooled meta-analysis to evaluate the efficacy and safety of micronized and ultra-micronized palmitoylethanolamide (PEA) on pain intensity in patients suffering from chronic and/or neuropathic pain.
  
  
  METHODS
  Pooled data analysis consisting of double-blind, controlled, and open-label clinical trials.
  
  
  METHODS
  Double-blind, controlled, and open-label clinical trials were selected consulting the PubMed, Google Scholar, and Cochrane databases, and proceedings of neuroscience meetings. The terms chronic pain, neuropathic pain, and micronized and ultra-micronized PEA were used for the search. Selection criteria included availability of raw data and comparability between tools used to diagnose and assess pain intensity. Raw data obtained by authors were pooled in one database and analyzed by the Generalized Linear Mixed Model. The changes in pain over time, measured by comparable tools, were also assessed by linear regression post-hoc analysis and the Kaplan-Meier estimate. Twelve studies were included in the pooled meta-analysis, 3 of which were double-blind trials comparing active comparators vs placebo, 2 were open-label trials vs standard therapies, and 7 were open-label trials without comparators.
  
  
  RESULTS
  Results showed that PEA elicits a progressive reduction of pain intensity significantly higher than control. The magnitude of reduction equals 1.04 points every 2 weeks with a 35% response variance explained by the linear model. In contrast, in the control group pain, reduction intensity equals 0.20 points every 2 weeks with only 1% of the total variance explained by the regression. The Kaplan-Meier estimator showed a pain score = 3 in 81% of PEA treated patients compared to only 40.9% in control patients by day 60 of treatment. PEA effects were independent of patient age or gender, and not related to the type of chronic pain.
  
  
  CONCLUSIONS
  Noteworthy, serious adverse events related to PEA were not registered and/or reported in any of the studies.
  
  
  CONCLUSIONS
  These results confirm that PEA might represent an exciting, new therapeutic strategy to manage chronic and neuropathic pain associated with neuroinflammation.
authors.affiliation: Assistant Professor, Department of Anesthesia and Pain Medicine, MESVA, University of L'Aquila, L'Aquila, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Paladini
authors.affiliation: Scientific Information and Documentation Center, Epitech Group, 35030 Saccolongo, Padua, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: Fusco
authors.affiliation: Clinical Research Advisor, Epitech Research Group, Via Luigi Einaudi 13, Padova, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Cenacchi
authors.affiliation: Adjunct Professor of Statistics, Department of Comparative Biomedicine, University of Padova, Padova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Schievano
authors.affiliation: Assistant Professor, Department of Anesthesia and Pain Medicine, MESVA, University of L'Aquila, L'Aquila, Italy.
authors.forename: Alba
authors.initials: A
authors.lastname: Piroli
authors.affiliation: University of L'Aquila, and Paolo Procacci Foundation, Via Tacito 7, 00193 Roma, Italy.
authors.forename: Giustino
authors.initials: G
authors.lastname: Varrassi
mesh_terms: D000328:Adult; D000577:Amides; D000700:Analgesics / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D059350:Chronic Pain / Q000175:diagnosis / Q000188:drug therapy*; D002986:Clinical Trials as Topic / Q000379:methods; D004983:Ethanolamines / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D059408:Pain Management / Q000379:methods*; D010169:Palmitic Acids / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000577:Amides; D000700:Analgesics; D004983:Ethanolamines; D010169:Palmitic Acids; C005958:palmidrol