Possible involvement of neuropeptide and neurotransmitter receptors in Adenomyosis

Accumulating data indicate that sensory nerve derived neuropeptides such as substance P and calcitonin gene related-protein (CGRP) can accelerate the progression of endometriosis via their respective receptors, so can agonists to their respective receptors receptor 1 (NK1R), receptor activity modifying protein 1 (RAMP-1) and calcitonin receptor-like receptor (CRLR). Adrenergic β2 receptor (ADRB2) agonists also can facilitate lesional progression. In contrast, women with endometriosis appear to have depressed vagal activity, concordant with reduced expression of α7 nicotinic acetylcholine receptor (α7nAChR). The roles of these receptors in adenomyosis are completely unknown.

Our results suggest that SP, CGRP and noradrenaline may promote, while acetylcholine may stall, the progression of adenomyosis through their respective receptors on adenomyotic lesions. Additionally, through the activation of the hypothalamic-pituitary-adrenal (HPA)-sympatho-adrenal-medullary (SAM) axes and the lesional overexpression of ADRB2, adenomyosis-associated dysmenorrhea and adenomyotic lesions may be mutually promotional, forming a viscous feed-forward cycle.

Adenomyotic tissue samples from 30 women with adenomyosis and control endometrial tissue samples from 24 women without adenomyosis were collected and subjected to immunohistochemistry analysis of RAMP1, CRLR, NK1R, ADRB2 and α7nAChR, along with their demographic and clinical information. The extent of tissue fibrosis was evaluated by Masson trichrome staining.

We found that the staining levels of NK1R, CRLR, RAMP1 and ADRB2 were all significantly elevated in adenomyotic lesions as compared with control endometrium. In contrast, α7nAChR staining levels were significantly reduced. The severity of dysmenorrhea correlated positively with lesional ADRB2 staining levels. Conclusions: Our results suggest that SP, CGRP and noradrenaline may promote, while acetylcholine may stall, the progression of adenomyosis through their respective receptors on adenomyotic lesions. Additionally, through the activation of the hypothalamic-pituitary-adrenal (HPA)-sympatho-adrenal-medullary (SAM) axes and the lesional overexpression of ADRB2, adenomyosis-associated dysmenorrhea and adenomyotic lesions may be mutually promotional, forming a viscous feed-forward cycle.