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Papers of the Week

Papers: 25 Feb 2023 - 3 Mar 2023

Basic Science

Animal Studies, Molecular/Cellular, Neurobiology, Pharmacology/Drug Development

Abdominal/Pelvic Pain

2023 Feb 24

J Neurochem


The voltage-gated sodium channel Na 1.7 underlies endometriosis-associated chronic pelvic pain.


Castro J, Maddern J, Chow CY, Tran P, Vetter I, King GF, Brierley SM


Chronic pelvic pain (CPP) is the primary symptom of endometriosis patients, but adequate treatments are lacking. Modulation of ion channels expressed by sensory nerves innervating the viscera have shown promise for the treatment of irritable bowel syndrome and overactive bladder. However, similar approaches for endometriosis-associated CPP remain underdeveloped. Here we examined the role of the voltage-gated sodium (Na ) channel Na 1.7 in i) the sensitivity of vagina-innervating sensory afferents and investigated whether ii) Na 1.7 inhibition reduces nociceptive signals from the vagina and iii) ameliorates endometriosis-associated CPP. The mechanical responsiveness of vagina-innervating sensory afferents was assessed with ex vivo single unit recording preparations. Pain evoked by vaginal distension (VD) was quantified by the visceromotor response (VMR) in vivo. In control mice, pharmacological activation of Na 1.7 with OD1 sensitised vagina-innervating pelvic afferents to mechanical stimuli. Using a syngeneic mouse model of endometriosis, we established that endometriosis sensitized vagina-innervating pelvic afferents to mechanical stimuli. The highly selective Na 1.7 inhibitor Tsp1a revealed that this afferent hypersensitivity occurred in a Na 1.7-dependent manner. Moreover, in vivo intra-vaginal treatment with Tsp1a reduced the exaggerated VMRs to VD that is characteristic of mice with endometriosis. Conversely, Tsp1a did not alter ex vivo afferent mechanosensitivity nor in vivo VMRs to VD in Sham control mice. Collectively, these findings suggest that Na 1.7 plays a crucial role in endometriosis-induced vaginal hyperalgesia. Importantly, Na 1.7 inhibition selectively alleviated endometriosis-associated CPP without the loss of normal sensation, suggesting that selective targeting of Na 1.7 could improve the quality of life of women with endometriosis.