Induction of the neurokinin 1 receptor by TNFα in endometriotic tissue provides the potential for neurogenic control over endometriotic lesion growth.

CONTEXT Endometriosis is characterized by the growth of ectopic endometrial tissue. Nerve fibers are frequently associated with ectopic lesions, and neurogenic inflammation may play a role in endometriosis. OBJECTIVE The purpose of this study was to determine the presence of tachykinin receptors in endometriotic lesions and the role of TNFα on their expression. DESIGN This study was an assessment of matching eutopic and ectopic endometrial tissue and peritoneal fluid from patients with endometriosis and an in vitro analysis of primary endometrial cells. SETTING The setting was a university hospital. PATIENTS Participants were premenopausal women undergoing laparoscopy. INTERVENTIONS Endometriotic lesions were removed surgically. MAIN OUTCOME MEASURES Tachykinin mRNA (TACR1/2) and protein (neurokinin 1 receptor [NK1R]) expression in both eutopic and ectopic endometrial tissue from patients with endometriosis and the correlation to peritoneal fluid TNFα were measured. Primary endometrial epithelial and stromal cells were assessed in vitro to determine the induction of TACR1/2 and NK1R expression after TNFα treatment. Cell viability of endometrial stromal cells after substance P exposure was also assessed. RESULTS Expression of both TACR1 and TACR2 mRNA was significantly higher in the ectopic than in the eutopic tissue. Both TACR1 mRNA and NK1R protein expression was significantly correlated with peritoneal fluid TNFα, and in vitro studies confirmed that TNFα treatment induced both TACR1 mRNA and NK1R protein expression in endometrial stromal cells. In endometrial stromal cells, substance P treatment enhanced cell viability, which was inhibited by a specific NK1R antagonist. CONCLUSIONS NK1R expression is induced in ectopic endometrial tissue by peritoneal TNFα. Induction of NK1R expression may permit endometriotic lesion maintenance via exposure to substance P.