Effect of PGD2 on middle meningeal artery and mRNA expression profile of L-PGD2 synthase and DP receptors in trigeminovascular system and other pain processing structures in rat brain

Sekeroglu, Aysegül; Jacobsen, Julie Mie; Jansen‐Olesen, Inger; Gupta, Saurabh; Sheykhzade, Majid; Olesen, Jes; Bhatt, Deepak

doi:10.1016/j.pharep.2016.09.015

Cited by 12 publications

(9 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because the net effect of PGD 2 treatment is the enhancement of the Na + current, PGD 2 appears to be pro-nociceptive, and DP1 may predominantly mediate that effect in these afferent nociceptors. A quantitative real-time RT-PCR analysis confirmed the predominance of Ptgdr1 (encoding DP1) expression over Ptgdr2 expression in both DRG and trigeminal neurons [116]. Nociceptor-specific Ptgdr1 expression has been replicated using different methods, such as a transcriptomic analysis using DRG neurons and an in situ hybridization assay using trigeminal neurons [117,118].…”

Section: Pgd 2 -Activated Dps (Pgd 2 Receptors)mentioning

confidence: 80%

Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception

Jang

Kim

Hwang

2020

J Neuroinflammation

163

View full text Add to dashboard Cite

Arachidonic acid-derived prostaglandins not only contribute to the development of inflammation as intercellular pro-inflammatory mediators, but also promote the excitability of the peripheral somatosensory system, contributing to pain exacerbation. Peripheral tissues undergo many forms of diseases that are frequently accompanied by inflammation. The somatosensory nerves innervating the inflamed areas experience heightened excitability and generate and transmit pain signals. Extensive studies have been carried out to elucidate how prostaglandins play their roles for such signaling at the cellular and molecular levels. Here, we briefly summarize the roles of arachidonic acid-derived prostaglandins, focusing on four prostaglandins and one thromboxane, particularly in terms of their actions on afferent nociceptors. We discuss the biosynthesis of the prostaglandins, their specific action sites, the pathological alteration of the expression levels of related proteins, the neuronal outcomes of receptor stimulation, their correlation with behavioral nociception, and the pharmacological efficacy of their regulators. This overview will help to a better understanding of the pathological roles that prostaglandins play in the somatosensory system and to a finding of critical molecular contributors to normalizing pain.

show abstract

Section: Pgd 2 -Activated Dps (Pgd 2 Receptors)mentioning

confidence: 80%

Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception

Jang

Kim

Hwang

2020

J Neuroinflammation

163

View full text Add to dashboard Cite

show abstract

“…We decided to focus on a gene that was up-regulated in the female IP: Prostaglandin-D2 synthase (Ptgds). Ptgds catalyzes the conversion of prostaglandin H 2 (PGH 2 ) to prostaglandin D2 (PGD 2 ) ( Figure 5A), which is known to be the most abundant prostaglandin in the brain (41, 42) and regulates nociception, sleep and temperature homeostasis (43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53). Prostaglandins are among the most widely studied of pain inducing molecules and many drugs are currently marketed as analgesics that target this class of molecules (54)(55)(56).…”

Section: Resultsmentioning

confidence: 99%

Sex differences in nociceptor translatomes contribute to divergent prostaglandin signaling in male and female mice

Tavares‐Ferreira

Ray

Sankaranarayanan

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: There are clinically relevant sex differences in acute and chronic pain mechanisms, but we are only beginning to understand their mechanistic basis. Transcriptome analyses of rodent whole dorsal root ganglion (DRG) have revealed sex differences, mostly in immune cells. We examined the transcriptome and translatome of the mouse DRG with the goal of identifying sex differences. Methods: We used Translating Ribosome Affinity Purification (TRAP) sequencing and behavioral pharmacology to test the hypothesis that nociceptor (Nav1.8 expressing neurons) translatomes would differ by sex. Results: We found 66 genes whose mRNA were sex-differentially bound to nociceptor ribosomes. Many of these genes have known neuronal functions but have not been explored in sex differences in pain. We focused on Ptgds, which was increased in female mice. The mRNA encodes the prostaglandin D2 (PGD2) synthesizing enzyme. We observed increased Ptgds protein and PGD2 in female mouse DRG. The Ptgds inhibitor AT-56 caused intense pain behaviors in male mice but was only effective at high doses in females. Conversely, female mice responded more robustly to another major prostaglandin, PGE2, than did male mice. Ptgds protein expression was also higher in female cortical neurons, suggesting DRG findings may be generalizable to other nervous system structures. Conclusions: Nociceptor TRAP sequencing (TRAP-seq) reveals unexpected sex differences in one of the oldest known nociceptive signaling molecule families, the prostaglandins. Our results demonstrate that translatome analysis reveals physiologically relevant sex differences important for fundamental protective behaviors driven by nociceptors.

show abstract

“…However, none of these proteins (including APOA1) showed any relationship with CPTs.L-PGDS was already found at unusually high concentrations in urine of MOH patients [13, 14]. The enzyme is highly expressed in leptomeninges [30] and is physiologically eliminated via the kidney. It is of interest for headaches and migraine, as it synthesizes PGD2, a strong vasodilator of the human middle cerebral artery [25], as well as a stimulus for the release of calcitonin gene-related peptide (CGRP) from trigeminal neurons [31].…”

Section: Discussionmentioning

confidence: 99%

Exploration of candidate serum biomarkers potentially related to the chronic pain condition in Medication–overuse headache

et al. 2019

View full text Add to dashboard Cite

Background Medication Overuse Headache (MOH) is a prevalent and disabling disorder resulting from the overuse of analgesic drugs, triptans or other acute headache medications. In previous proteomic studies, several proteins have been found at high concentrations in the urine of MOH patients and in the serum of rats with neuropathic pain. The aim of this study was to compare the serum levels of lipocalin-type Prostaglandin D2 synthase (L-PGDS), Vitamin D-binding protein (VDBP), apolipoprotein E (APOE) and apolipoprotein A1 (APOA1) in MOH patients and healthy individuals, further exploring their relationship with cutaneous pain thresholds (CPTs) in the territories innervated by the trigeminal nerve. Methods Sixty-nine MOH patients and 42 age- and sex-matched healthy volunteers were enrolled in the study. Von Frey-like filaments were applied to the skin territories innervated by the trigeminal nerve, to determine the CPTs. L-PGDS, VDBP, APOE and APOA1 were quantified in the serum by Enzyme-linked Immunosorbent Assay (ELISA). Clinical and laboratory data were collected. Comparisons between MOH patients and healthy individuals were performed using independent t test or χ2 test. To correlate serum proteins with CPTs, Pearson correlation coefficient or Spearman’s rank correlation coefficient were used. Results CPTs were lower among MOH patients. L-PGDS, VDBP and APOE had significantly different serum concentrations between groups (p < 0.01), but no correlation was found with CPTs. APOA1 serum concentrations did not differ between patients and healthy individuals. Conclusions L-PGDS, VDBP and APOE had abnormal serum levels in MOH patients, confirming their alteration in some conditions of chronic headache and neuropathic pain. However, they had no relationship with CPTs. The in-depth study of serum proteins represents a promising approach for a better understanding of MOH, as well as the detection of candidate biomarkers for chronic headache or the risks associated with overuse medications.

show abstract

Effect of PGD2 on middle meningeal artery and mRNA expression profile of L-PGD2 synthase and DP receptors in trigeminovascular system and other pain processing structures in rat brain

Abstract: High expression of DP mRNA in the TG and DRG suggest that PGD might play a role in migraine pathophysiology. Activation of the DP receptor in MMA was mainly responsible for vasodilation induced by PGD infusion.

Cited by 12 publications

References 40 publications

Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception

Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception

Sex differences in nociceptor translatomes contribute to divergent prostaglandin signaling in male and female mice

Exploration of candidate serum biomarkers potentially related to the chronic pain condition in Medication–overuse headache

Contact Info

Product

Resources

About