Presence and upregulation of Transient Receptor Potential Vanilloid 1 (TRPV1) and Ankyrin 1 (TRPA1) in translational rat endometriosis model

Abstract

The Transient Receptor Potential Vanilloid 1 (TRPV1) and Ankyrin 1 (TRPA1) are non-selective cation channels predominantly localized on capsaicin-sensitive sensory neurons; however both receptors have been described in non-neuronal tissues. It has been published that both receptors upregulated in peritoneal endometriosis in humans. Our research group demonstrated that TRPA1 and TRPV1 expression is elevated in human deep infiltrating endometriosis (DIE) lesions and the receptors have an estrogen-dependent expression pattern in rat endometrium. Here, we investigated the expression changes of TRPA1/V1 and the role of the capsaicin-sensitive sensory-nerve endings in a rat model of peritoneal endometriosis. Peritoneal endometriosis was surgically induced in 8-week-old female rats (n=7-7) for 2-weeks (acute condition) and 8-weeks (chronic condition). TRPA1/V1 mRNAs were quantified with quantitative polymerase chain reaction (qPCR). The expression levels were compared with the results obtained earlier from human DIE samples. The blockade of the TRPA1/V1 expressing capsaicin-sensitive nerve endings was induced with resiniferatoxin (RTX), followed by the measurement of the weight and size of the endometriosis lesions. We detected TRPV1 and TRPA1 mRNA in normal rat endometrium, their expression was not altered in sham-operated animals. In chronic, but not in acute endometriosis the expression was significantly elevated in the lesions, which results are consistent with our previous findings in human DIE. The elimination of capsaicin-sensitive nerve endings decreased the weight of the endometriosis lesions while the size of the ectopic tissue was not altered. Taken together, our results obtained from the rat endometriosis model are consistent with the previous human results, therefore this model is considered to have translational significance and it is suitable for functional analysis of the ion channels. The local, non-neuronal TRPA1 and TRPV1 might play a role in inflammation and sensory neuronal activation in endometriosis related pain, which is mediated by a broad range of pro-inflammatory molecules.