Nociceptin/Orphanin FQ Opioid Peptide-Receptor Expression in the Endometriosis-Associated Nerve Fibers-Possible Treatment Option?

Endometriosis (EM) is a chronic inflammatory disease affecting millions of women worldwide. Chronic pelvic pain is one of the main problems of this condition, leading to quality-of-life impairment. Currently, available treatment options are not able to treat these women accurately. A better understanding of the pain mechanisms would be beneficial to integrate additional therapeutic management strategies, especially specific analgesic options. To understand pain in more detail, nociceptin/orphanin FQ peptide (NOP) receptor expression was analyzed in EM-associated nerve fibers (NFs) for the first time. Laparoscopically excised peritoneal samples from 94 symptomatic women (73 with EM and 21 controls) were immunohistochemically stained for NOP, protein gene product 9.5 (PGP9.5), substance P (SP), calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP). Peritoneal NFs of EM patients and healthy controls were positive for NOP and often colocalized with SP-, CGRP-, TH-, and VIP-positive nerve fibers, suggesting that NOP is expressed in sensory and autonomic nerve fibers. In addition, NOP expression was increased in EM associate NF. Our findings highlight the potential of NOP agonists, particularly in chronic EM-associated pain syndromes and deserve further study, as the efficacy of NOP-selective agonists in clinical trials.

Endometriosis and Opioid Receptors: Are Opioids a Possible/Promising Treatment for Endometriosis?

Endometriosis (EM), defined as the presence of endometrial-like tissue with surrounding smooth muscle cells outside the uterus, is a disregarded gynecological disease reported to affect 6-10% of women of reproductive age, with 30-50% of them suffering from chronic pelvic pain and infertility. Since the exact pathogenic mechanisms of EM are still unclear, no curative therapy is available. As pain is an important factor in EM, optimal analgesia should be sought, which to date has been treated primarily with non-steroidal anti-inflammatory drugs (NSAIDs), metamizole or, in extreme cases, opioids. Here, we review the pain therapy options, the mechanisms of pain development in EM, the endogenous opioid system and pain, as well as the opioid receptors and EM-associated pain. We also explore the drug abuse and addiction to opioids and the possible use of NOP receptors in terms of analgesia and improved tolerability as a target for EM-associated pain treatment. Emerging evidence has shown a promising functional profile of bifunctional NOP/MOP partial agonists as safe and nonaddictive analgesics. However, until now, the role of NOP receptors in EM has not been investigated. This review offers a thought which still needs further investigation but may provide potential options for relieving EM-associated pain.

Effect of epigallocatechin-3-gallate on the status of DNA methylation of E-cadherin promoter region on endometriosis mouse.

AIM: To evaluate whether epigallocatechin-3-gallate acts on endometriosis mouse, and changes the status of DNA methylation of E-cadherin promoter region. METHODS: According to our previous research, the tracing nude mouse model of endometriosis was built up and randomly divided into three groups: control group (group A), epigallocatechin-3-gallate group (group B) and decitabine group (group C). Normal saline, epigallocatechin-3-gallate and decitabine were isometrically intraperitoneally injected into each group once in 2 days. In this period, the growth situations of lesions were monitored by living image system. After 16 days, the lesions were taken out and the distribution of E-cadherin and its methylated situation of promoter region were analyzed. RESULTS: The region of interest of ectopic lesion increased from 4th to 16th day in group A (P < 0.01); in group B and C, the region of interest of ectopic lesion increased in the 0-8th day (P < 0.01), and decreased in the 8-16th day (P < 0.01). The positive expression rate of E-cadherin in group C was higher than group B, and group B was higher than group A (P < 0.01). The DNA methylation status of E-cadherin promoter region in group A was higher than group B, and group B was higher than group C (P < 0.01). CONCLUSION: Epigallocatechin-3-gallate may inhibit the growth of endometrial lesion, affect the expression of E-cadherin on the cell membrane and reduce the status of DNA methylation of E-cadherin promoter region.