Endocannabinoids and Related Lipids in Chronic Pain: Analytical and Clinical Aspects

Stensson, Niclas

doi:10.3384/diss.diva-147653

Cited by 2 publications

(3 citation statements)

References 215 publications

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“…N-arachidonoylethanolamine is a partial agonist at cannabinoid receptors, the affinity for CB1 (predominantly expressed in the central nervous system) being 4 times higher than that for CB2 (mainly found on cells of the immune system). 52 In chronic neurological disorders, altered levels of endocannabinoids such as AEA can conceptually be viewed either as a maladaptive mechanism contributing to disease or as an adaptive response aimed at restoring homeostasis. 15,33 Viewed from that perspective, and because AEA is generally considered to be antinociceptive (eg, by activation of presynaptic CB1 52 ), one could speculate that higher serum levels of AEA in painful diabetic neuropathy would mirror a compensatory mechanism, the organism trying to restore homeostasis in those more prone to developing a pain phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…52 In chronic neurological disorders, altered levels of endocannabinoids such as AEA can conceptually be viewed either as a maladaptive mechanism contributing to disease or as an adaptive response aimed at restoring homeostasis. 15,33 Viewed from that perspective, and because AEA is generally considered to be antinociceptive (eg, by activation of presynaptic CB1 52 ), one could speculate that higher serum levels of AEA in painful diabetic neuropathy would mirror a compensatory mechanism, the organism trying to restore homeostasis in those more prone to developing a pain phenotype. Along the same interpretational lines, one could argue that the lower levels of AEA in severe neuropathic pain (see Online Supplement 1, available at http:// links.lww.com/PAIN/B896) would be akin to having a less efficacious "endocannabinoid pain brake."…”

Section: Discussionmentioning

confidence: 99%

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Serum levels of endocannabinoids and related lipids in painful vs painless diabetic neuropathy: results from the Pain in Neuropathy Study

Bäckryd

Themistocleous

Stensson

et al. 2023

Pain

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N-arachidonoylethanolamine (also known as anandamide) and 2-arachidonoylglycerol are activators of the cannabinoid receptors. The endocannabinoid system also includes structurally and functionally related lipid mediators that do not target cannabinoid receptors, such as oleoylethanolamide, palmitoylethanolamide, and stearoylethanolamide. These bioactive lipids are involved in various physiological processes, including regulation of pain. The primary aim of the study was to analyze associations between serum levels of these lipids and pain in participants in the Pain in Neuropathy Study, an observational, cross-sectional, multicentre, research project in which diabetic patients with painless or painful neuropathy underwent deep phenotyping. Our hypothesis was that painful neuropathy would be associated with higher levels of the 5 lipids compared with painless neuropathy. Secondary aims were to analyze other patient-reported outcome measures and clinical data in relationship to lipid levels. The lipid mediators were analyzed in serum samples using liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum levels of anandamide were significantly higher in the painful group, but the effect size was small (Cohen d = 0.31). Using cluster analysis of lipid data, patients were dichotomized into a “high-level” endocannabinoid group and a “low-level” group. In the high-level group, 61% of patients had painful neuropathy, compared with 45% in the low-level group (P = 0.039). This work is of a correlative nature only, and the relevance of these findings to the search for analgesics targeting the endocannabinoid system needs to be determined in future studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Serum levels of endocannabinoids and related lipids in painful vs painless diabetic neuropathy: results from the Pain in Neuropathy Study

Bäckryd

Themistocleous

Stensson

et al. 2023

Pain

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“…Therefore, they are known as bioactive lipid mediators. After the identification of the first lipid mediator, arachidonoyl-ethanolamide (AEA) of the ECS, (also known as anandamide) [ 13 , 14 , 15 ], different biomolecules associated with this family were discovered. The most vital molecules are 2-arachidonoyl-glycerol (2AG) and its isomer 1AG among monoacyl-glycerols; palmitoyl-ethanolamide (PEA); oleyl-ethanolamide (OEA), and the N-acyl-ethanolamides [ 16 , 17 , 18 ].…”

Section: The Endocannabinoid Systemmentioning

confidence: 99%

Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

et al. 2021

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In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

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Endocannabinoids and Related Lipids in Chronic Pain: Analytical and Clinical Aspects

Cited by 2 publications

References 215 publications

Serum levels of endocannabinoids and related lipids in painful vs painless diabetic neuropathy: results from the Pain in Neuropathy Study

Serum levels of endocannabinoids and related lipids in painful vs painless diabetic neuropathy: results from the Pain in Neuropathy Study

Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

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