The voltage-gated sodium channel NaV1.7 underlies endometriosis-associated chronic pelvic pain

Joel Castro, Jessica Maddern, Chun Yuen Chow, Poanna Tran, Irina Vetter, Glenn F King, Stuart M Brierley
Journal of neurochemistry · 2023 · vol. 168(11) , pp. 3760–3776 · doi:10.1111/jnc.15795 · PMID:36840383 · W4321996774
article OA: hybrid CC0 ⤵ 3 in-corpus citations
🔓 Open OA copy View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This study found that NaV1.7 channels are essential for endometriosis-induced vaginal hypersensitivity and that inhibiting NaV1.7 can alleviate associated chronic pelvic pain.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

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 has 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 (NaV) channel NaV1.7 in (i) the sensitivity of vagina-innervating sensory afferents and investigated whether (ii) NaV1.7 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 NaV1.7 with OD1 sensitised vagina-innervating pelvic afferents to mechanical stimuli. Using a syngeneic mouse model of endometriosis, we established that endometriosis sensitised vagina-innervating pelvic afferents to mechanical stimuli. The highly selective NaV1.7 inhibitor Tsp1a revealed that this afferent hypersensitivity occurred in a NaV1.7-dependent manner. Moreover, in vivo intra-vaginal treatment with Tsp1a reduced the exaggerated VMRs to VD which 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 NaV1.7 plays a crucial role in endometriosis-induced vaginal hyperalgesia. Importantly, NaV1.7 inhibition selectively alleviated endometriosis-associated CPP without the loss of normal sensation, suggesting that selective targeting of NaV1.7 could improve the quality of life of women with endometriosis.

My notes (saved in your browser only)

Condition tags

endometriosischronic_pelvic_painirritable_bowel_syndrome

MeSH descriptors

Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (68)

Cited by (3)

Source provenance

europepmc
last seen: 2026-06-11T06:19:48.454388+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-06-11T06:18:57.514842+00:00
License: CC0 · commercial use OK