Abstract

Background N-acylethanolamines (NAEs) are endogenous compounds that regulate inflammation and pain. These include the cannabinoid ligand anandamide (AEA) and the peroxisome proliferator-activated receptor-α ligand palmitoylethanolamide (PEA). Little is known as to the levels of NAEs in pain states in human, particularly in the skeletal muscle. The aim of this study was to investigate the levels of these lipid mediators in muscle dialysate from women with chronic neck-/shoulder pain compared to healthy controls.MethodsEleven women with chronic neck-/shoulder pain and eleven healthy women participated in this study. All participants went through microdialysis procedures in the trapezius muscle. Muscle dialysate samples were collected during four hours and analysed by nano liquid chromatography tandem mass spectrometry (nLC-MS/MS).ResultsWe were able to detect AEA, PEA, N-stearoylethanolamine (SEA) and 2-arachidonoylglycerol (2-AG) in a single chromatographic run. Of the NAEs studied, PEA and SEA were clearly detectable in the muscle microdialysate samples. The muscle dialysate levels of PEA and SEA were significantly higher in myalgic subjects compared to healthy controls.ConclusionThis study demonstrates that microdialysis in combination with mass spectrometry can be used for analysing NAE's in human muscle tissue regularly over time. Furthermore the significant group differences in the concentration of PEA and SEA in this study might fill an important gap in our knowledge of mechanisms in chronic myalgia in humans. In the long run this expanded understanding of nociceptive and anitinociceptive processes in the muscle may provide a base for ameliorating treatment and rehabilitation of pain.

Highlights

  • Chronic pain is associated with disability, low quality of life and substantial socioeconomic costs

  • We have developed a method allowing determination of NAEs in small samples of muscle dialysate and used the method to demonstrate that the levels of PEA and SEA are significantly elevated in women with chronic trapezius myalgia compared to healthy controls

  • The present study demonstrates that levels of PEA and SEA are both increased in dialysate samples from women with chronic trapezius myalgia compared to healthy controls, and that this increase is rather stable over time and not obviously affected by the standardized low-force repetitive exercise work associated with a significant pain intensity increase

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Summary

Introduction

Chronic pain is associated with disability, low quality of life and substantial socioeconomic costs. Common chronic pain conditions are localized neck-shoulder pain including trapezius myalgia, which has a prevalence of 10–20% in the community [1]. The understanding of mechanisms, including the peripheral balances between nociceptive and anitinociceptive processes, behind chronic myalgia is incomplete. N-acylethanolamines (NAEs) are endogenous compounds that regulate inflammation and pain. These include the cannabinoid ligand anandamide (AEA) and the peroxisome proliferator-activated receptor-a ligand palmitoylethanolamide (PEA). Little is known as to the levels of NAEs in pain states in human, in the skeletal muscle. The aim of this study was to investigate the levels of these lipid mediators in muscle dialysate from women with chronic neck-/shoulder pain compared to healthy controls

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