*6.2. Opioid Receptors*

The endogenous opioid peptides (EOPs) are derived from proopiomelanocortin (POMC), proenkephalin (PENK), and prodynorphin (PDYN) precursors and exert their effects by binding to the G-protein-coupled receptors δ-opioid receptor (DOR), κ-opioid receptor (KOR), µ-opioid receptor (MOR), and nociceptin/orphanin FQ opioid peptide receptor (NOP) [59,60]. The peripheral opioid system plays a crucial role in inflammatory reactions and neurogenic inflammation since this system is activated and modulated by inflammation. During this process, analgetic factors such as anti-inflammatory cytokines and opioid peptides are released, promoting antinociceptive actions. In chronic inflammation, the release of anti-inflammatory mediators and opioid peptides is decreased, improving the perpetuation of inflammation. Since EM is a chronic inflammatory disease with a disturbing pain mediation and analgesia, disruption in the expression of opioid peptides or opioid receptors might be involved in the inflammatory condition and pain pathogenesis in this disease and alterations in the expression of those receptors and their respective ligands should be urgently investigated. Indeed, the mRNA of three opioid peptide precursors has been described in the endometrium [61]. Finally, DOR and KOR have been described in Ishikawa human endometrial cells, while MOR is absent [62,63]; in fact, MOR has been localized only in the uterine luminal epithelium cells of the pregnant mouse [64] and in EM stromal cells [65–67]. NOP has not been tested. The proven presence of most of the compounds of the opioid system in the endometrium denotes the role of this system in processes occurring in the endometrium, including EM.
