Beyond the classic eicosanoids: Peripherally-acting oxygenated metabolites of polyunsaturated fatty acids mediate pain associated with tissue injury and inflammation

Shapiro, Haim; Singer, Pierre; Ariel, Amiram

doi:10.1016/j.plefa.2016.03.001

Cited by 42 publications

(21 citation statements)

References 153 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alterations in oxylipin concentrations have been described for numerous diseases, including Alzheimer’s disease [20, 21], chronic pain [15, 22], diabetes [23], and cardiovascular disease [24]. Although these diseases are complex and multifactorial, they may share common pathological processes including neuroinflammation/inflammation [25], oxidative stress [2, 26], nociception [27], disrupted glucose metabolism [28, 29], and endothelial cell activation [30]. These processes consist of distinct biochemical cascades, but are closely intertwined with each other [27, 31–35].…”

Section: Introductionmentioning

confidence: 99%

“…Although these diseases are complex and multifactorial, they may share common pathological processes including neuroinflammation/inflammation [25], oxidative stress [2, 26], nociception [27], disrupted glucose metabolism [28, 29], and endothelial cell activation [30]. These processes consist of distinct biochemical cascades, but are closely intertwined with each other [27, 31–35]. Oxylipins are reported to stimulate, oppose, or otherwise modulate these biochemical cascades, and influence these processes in an interactive ways.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lipidomic profiling of targeted oxylipins with ultra-performance liquid chromatography-tandem mass spectrometry

et al. 2018

View full text Add to dashboard Cite

Oxylipins are bioactive mediators that play diverse roles in (patho)physiology. We developed a sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous profiling of 57 targeted oxylipins derived from five major n-6 and n-3 polyunsaturated fatty acids (PUFAs) that serve as oxylipin precursors, including linoleic (LA), arachidonic (AA), alpha-linolenic (ALA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids. The targeted oxylipin panel provides broad coverage of lipid mediators and pathway markers generated from cyclooxygenases, lipoxygenases, cytochrome P450 epoxygenases/hydroxylases, and non-enzymatic oxidation pathways. The method is based on combination of protein precipitation and solid-phase extraction (SPE) for sample preparation, followed by UPLC-MS/MS. This is the first methodology to incorporate four hydroxy-epoxy-octadecenoic acids and four keto-epoxy-octadecenoic acids into an oxylipin profiling network. The novel method achieves excellent resolution and allows in-depth analysis of isomeric and isobaric species of oxylipin extracts in biological samples. The method was quantitatively characterized in human plasma with good linearity (R = 0.990-0.999), acceptable reproducibility (relative standard deviation (RSD) < 20% for the majority of analytes), accuracy (67.8 to 129.3%) for all analytes, and recovery (66.8-121.2%) for all analytes except 5,6-EET. Ion enhancement effects for 28% of the analytes in tested concentrations were observed in plasma, but were reproducible with RSD < 17.2%. Basal levels of targeted oxylipins determined in plasma and serum are in agreement with those previously reported in literature. The method has been successfully applied in clinical and preclinical studies.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lipidomic profiling of targeted oxylipins with ultra-performance liquid chromatography-tandem mass spectrometry

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Another possibility was the activation of PAR 2 because of its abundant expression in sensory neurons and involvement in inflammatory pain. 11,33 Swab application of the PAR 2 selective antagonist FSLLRY-NH 2 significantly increased the declined head withdrawal threshold in the model compared with the vehicle (Dunnett post hoc test, P < 0.05; Figure 4(c)). The same application did not alter the increase in spontaneous mouth rubbing (Figure 4(d)).…”

Section: Resultsmentioning

confidence: 92%

“…In the ELISA assays, IL-1β, IL-6, and TNF-α were upregulated on day 1 in the WiM model relative to the sham ( t test, P < 0.01 for IL-1β and P < 0.05 for IL-6 and TNF-α; Supplementary Figure 1(a)–(c)). However, there was no significant difference in bradykinin, which is a well-known inflammatory pain inducer, 11 between the sham and WiM model (Supplementary Figure 1(d)).…”

Section: Resultsmentioning

confidence: 94%

See 1 more Smart Citation

Prostanoid-dependent spontaneous pain and PAR₂-dependent mechanical allodynia following oral mucosal trauma

et al. 2017

View full text Add to dashboard Cite

During dental treatments, intraoral appliances frequently induce traumatic ulcers in the oral mucosa. Such mucosal injury-induced mucositis leads to severe pain, resulting in poor quality of life and decreased cooperation in the therapy. To elucidate mucosal pain mechanisms, we developed a new rat model of intraoral wire-induced mucositis and investigated pain mechanisms using our proprietary assay system for conscious rats. A thick metal wire was installed in the rats between the inferior incisors for one day. In the mucosa of the mandibular labial fornix region, which was touched with a free end of the wire, traumatic ulcer and submucosal abscess were induced on day 1. The ulcer was quickly cured until next day and abscess formation was gradually disappeared until five days. Spontaneous nociceptive behavior was induced on day 1 only, and mechanical allodynia persisted over day 3. Antibiotic pretreatment did not affect pain induction. Spontaneous nociceptive behavior was sensitive to indomethacin (cyclooxygenase inhibitor), ONO-8711 (prostanoid receptor EP1 antagonist), SB-366791, and HC-030031 (TRPV1 and TRPA1 antagonists, respectively). Prostaglandin E2 and 15-deoxyΔ12,14-prostaglandin J2 were upregulated only on day 1. In contrast, mechanical allodynia was sensitive to FSLLRY-NH2 (protease-activated receptor PAR2 antagonist) and RN-1734 (TRPV4 antagonist). Neutrophil elastase, which is known as a biased agonist for PAR2, was upregulated on days 1 to 2. These results suggest that prostanoids and PAR2 activation elicit TRPV1- and TRPA1-mediated spontaneous pain and TRPV4-mediated mechanical allodynia, respectively, independently of bacterial infection, following oral mucosal trauma. The pathophysiological pain mechanism suggests effective analgesic approaches for dental patients suffering from mucosal trauma-induced pain.

show abstract

Endocannabinoid-Binding Receptors as Drug Targets

Gómez‐Cañas

Rodríguez‐Cueto

Satta

et al. 2022

Methods in Molecular Biology

View full text Add to dashboard Cite

Beyond the classic eicosanoids: Peripherally-acting oxygenated metabolites of polyunsaturated fatty acids mediate pain associated with tissue injury and inflammation

Cited by 42 publications

References 153 publications

Lipidomic profiling of targeted oxylipins with ultra-performance liquid chromatography-tandem mass spectrometry

Lipidomic profiling of targeted oxylipins with ultra-performance liquid chromatography-tandem mass spectrometry

Prostanoid-dependent spontaneous pain and PAR₂-dependent mechanical allodynia following oral mucosal trauma

Endocannabinoid-Binding Receptors as Drug Targets

Contact Info

Product

Resources

About

Beyond the classic eicosanoids: Peripherally-acting oxygenated metabolites of polyunsaturated fatty acids mediate pain associated with tissue injury and inflammation

Cited by 42 publications

References 153 publications

Lipidomic profiling of targeted oxylipins with ultra-performance liquid chromatography-tandem mass spectrometry

Lipidomic profiling of targeted oxylipins with ultra-performance liquid chromatography-tandem mass spectrometry

Prostanoid-dependent spontaneous pain and PAR2-dependent mechanical allodynia following oral mucosal trauma

Endocannabinoid-Binding Receptors as Drug Targets

Contact Info

Product

Resources

About

Prostanoid-dependent spontaneous pain and PAR₂-dependent mechanical allodynia following oral mucosal trauma