The Relationship of Endocannabinoidome Lipid Mediators With Pain and Psychological Stress in Women With Fibromyalgia: A Case-Control Study

Stensson, Niclas; Ghafouri, Nazdar; Ernberg, Malin; Mannerkorpi, Kaisa; Kosek, Eva; Gerdle, Björn; Ghafouri, Bijar

doi:10.1016/j.jpain.2018.05.008

Cited by 33 publications

(45 citation statements)

References 55 publications

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“…123 Palmitoylethanolamide blood levels also increase in pain processing disorders such as fibromyalgia and in individuals with widespread pain. 124,125 There have been multiple prospective observational and randomized PEA trials that have been largely used as an add-on analgesic nutraceutical (Table 1). We found 19 studies and 5 randomized controlled trials (RCTs).…”

Section: Painmentioning

confidence: 99%

The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review

Davis

Behm

Mehta

et al. 2019

Am J Hosp Palliat Care

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Palmitoylethanolamide (PEA) is a nutraceutical endocannabinoid that was retrospectively discovered in egg yolks. Feeding poor children with known streptococcal infections prevented rheumatic fever. Subsequently, it was found to alter the course of influenza. Unfortunately, there is little known about its pharmacokinetics. Palmitoylethanolamide targets nonclassical cannabinoid receptors rather than CB1 and CB2 receptors. Palmitoylethanolamide will only indirectly activate classical cannabinoid receptors by an entourage effect. There are a significant number of prospective and randomized trials demonstrating the pain-relieving effects of PEA. There is lesser evidence of benefit in patients with nonpain symptoms related to depression, Parkinson disease, strokes, and autism. There are no reported drug–drug interactions and very few reported adverse effects from PEA. Further research is needed to define the palliative benefits to PEA.

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Section: Painmentioning

confidence: 99%

The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review

Davis

Behm

Mehta

et al. 2019

Am J Hosp Palliat Care

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“…There is increasing evidence that not only central mechanisms are essential for the presentation and the maintenance of the clinical picture in FM patients. Hence, in addition to the studies reporting central alterations (e.g., anatomical and functional changes in the brain, activation of glia cells, opioidergic dysregulation, impaired top-down modulation and nociception-driven amplification of neural signalling), several studies have shown systemic and peripheral changes in FM, e.g., regarding cytokine profile 11 – 13 , inflammatory lipids 14 , alteration of different metabolites and changes of the gut microbiota 15 – 17 , and altered protein changes in muscles 18 – 20 . So far, no clinically validated biomarkers for FM have been established.…”

Section: Introductionmentioning

confidence: 99%

Significant correlation between plasma proteome profile and pain intensity, sensitivity, and psychological distress in women with fibromyalgia

Wåhlén

Ernberg

Mannerkorpi

et al. 2020

Sci Rep

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Fibromyalgia (FM) is a complex pain condition where the pathophysiological and molecular mechanisms are not fully elucidated. The primary aim of this study was to investigate the plasma proteome profile in women with FM compared to controls. The secondary aim was to investigate if plasma protein patterns correlate with the clinical variables pain intensity, sensitivity, and psychological distress. Clinical variables/background data were retrieved through questionnaires. Pressure pain thresholds (PPT) were assessed using an algometer. The plasma proteome profile of FM (n = 30) and controls (n = 32) was analyzed using two-dimensional gel electrophoresis and mass spectrometry. Quantified proteins were analyzed regarding group differences, and correlations to clinical parameters in FM, using multivariate statistics. Clear significant differences between FM and controls were found in proteins involved in inflammatory, metabolic, and immunity processes. Pain intensity, PPT, and psychological distress in FM had associations with specific plasma proteins involved in blood coagulation, metabolic, inflammation and immunity processes. This study further confirms that systemic differences in protein expression exist in women with FM compared to controls and that altered levels of specific plasma proteins are associated with different clinical parameters.

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“…26 Moreover, PEA has been reported to inhibit glutamate release in rat cerebrocortical nerve terminals. 27 Previously, we compared alterations of circulating levels of eCBs and NAEs 28,29 and glutamate 30 in subjects with chronic widespread pain and healthy controls (HC); however, no clear biological roles of this alteration were determined. Here, we investigate the effect of a 30-min dynamic load arm cycling intervention with respect to circulating levels of eCBs, NAEs and glutamate in subjects with chronic neck and shoulder pain (CNSP) and in HC.…”

Section: Introductionmentioning

confidence: 99%

Altered relationship between anandamide and glutamate in circulation after 30 min of arm cycling: A comparison of chronic pain subject with healthy controls

Stensson

Grimby-Ekman²

2019

Mol Pain

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The insufficient knowledge of biochemical mechanisms behind the emergence and maintenance of chronic musculoskeletal pain conditions constrains the development of diagnostic and therapeutic tools for clinical use. However, physical activity and exercise may improve pain severity and physical function during chronic pain conditions. Nevertheless, the biochemical consequences of physical activity and exercise in chronic pain need to be elucidated to increase the precision of this therapeutic tool in chronic pain treatment. The endocannabinoid system has been suggested to play an important role in exercise-induced reward and pain inhibition. Moreover, glutamatergic signalling has been suggested as an important factor for sensation and transmission of pain. In addition, a link has been established between the endocannabinoid system and glutamatergic pathways. This study examines the effect of dynamic load arm cycling (30 min) on levels of lipid mediators related to the endocannabinoid system and glutamate in plasma of chronic pain subjects and pain-free controls. Pain assessments and plasma levels of arachidonoylethanolamide (anandamide), 2-aracidonoylglycerol, oleoylethanolamide, palmitoylethanolamide, stearoylethanolamide and glutamate from 21 subjects with chronic neck pain (chronic pain group) and 11 healthy controls were analysed pre and post intervention of dynamic load arm cycling. Pain intensity was significantly different between groups pre and post exercise. Post exercise, anandamide levels were significantly decreased in health controls but not in the chronic pain group. A strong positive correlation existed between anandamide and glutamate in the control group post exercise but not in the chronic pain group. Moreover, the glutamate/anandamide ratio increased significantly in the control group and differed significantly with the chronic pain group post exercise. The altered relationship between anandamide and glutamate after the intervention in the chronic pain group might reflect alterations in the endocannabinoid-glutamate mechanistic links in the chronic pain group compared to the painfree control group.

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The Relationship of Endocannabinoidome Lipid Mediators With Pain and Psychological Stress in Women With Fibromyalgia: A Case-Control Study

Cited by 33 publications

References 55 publications

The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review

The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review

Significant correlation between plasma proteome profile and pain intensity, sensitivity, and psychological distress in women with fibromyalgia

Altered relationship between anandamide and glutamate in circulation after 30 min of arm cycling: A comparison of chronic pain subject with healthy controls

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