Abstract

BackgroundChronic musculoskeletal pain may be associated with changes in the balance of algogenic and anti-nociceptive compounds, and such changes may be visible in plasma samples. We have undertaken an exploratory study to measure the levels of endocannabinoids, related N-acylethanolamines and oxylipins (primarily those derived from linoleic acid) in plasma samples from women with chronic neck pain (NP) and chronic widespread pain (CWP), and to investigate whether the observed levels are associated with the pain experienced by these women.MethodsBlood samples from 35 women with NP, 15 with CWP and 27 age-matched controls were analysed for the lipids using ultra performance liquid chromatography coupled to tandem mass spectrometry. Current pain (“NRSday”) and the average pain during the last week (“NRSweek”) were rated by the participants using a numerical rating scale.ResultsThere were no significant differences in the plasma concentrations of the fifteen lipids investigated between the women with pain and the controls. However, significant correlations were seen for the NP group between the NRSday scores and the plasma concentrations of the linoleic acid derivatives 9- and 13-hydroxy-octadecadienoic acid (Spearman’s rho values 0.51 [P = 0.0016]) and 0.53 [P = 0.0011], respectively).ConclusionsThe data obtained in this exploratory study indicate that although no group differences are seen in plasma lipid concentrations, there is an association between the NRSday scores and the 9- and 13-hydroxy-octadecadienoic acid levels. Whether or not the association reflects a causality (i.e. that the circulating lipids contribute to the perceived pain of the pain participants), requires further investigation.

Highlights

  • Chronic musculoskeletal pain may be associated with changes in the balance of algogenic and antinociceptive compounds, and such changes may be visible in plasma samples

  • Endogenous pain modulation is not restricted to glutamate, lactate and serotonin alone, and there are a number of lipids, including N-acylethanolamines (NAEs), endocannabinoids and oxylipins derived from linoleic acid that affect pain perception

  • With respect to the NAEs, the most well-studied is arachidonoylethanolamide (AEA, anandamide), which produces its actions in the body primarily via effects upon cannabinoid (CB) receptors, it can act upon transient receptor potential vanilloid 1 (TRPV1) receptors, under conditions of inflammation [7]

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Summary

Introduction

Chronic musculoskeletal pain may be associated with changes in the balance of algogenic and antinociceptive compounds, and such changes may be visible in plasma samples. We have undertaken an exploratory study to measure the levels of endocannabinoids, related N-acylethanolamines and oxylipins (primarily those derived from linoleic acid) in plasma samples from women with chronic neck pain (NP) and chronic widespread pain (CWP), and to investigate whether the observed levels are associated with the pain experienced by these women. The raised interstitial concentrations of glutamate and lactate seen in muscle dialysates from CWP patients were seen in plasma from the same individuals [5] In another microdialysis study investigating controls and individuals with trapezius myalgia, a positive correlation was seen between baseline pain and the interstitial levels of serotonin, an important painsignalling molecule [6]. Endogenous pain modulation is not restricted to glutamate, lactate and serotonin alone, and there are a number of lipids, including N-acylethanolamines (NAEs), endocannabinoids and oxylipins derived from linoleic acid that affect pain perception. Other members of the NAE family, such as linoleoylethanolamide (LEA), are less well investigated

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