Decreased concentration of protease inhibitors: Possible contributors to allodynia and hyperalgesia in women with vestibulodynia

Objective Women with vestibulodynia exhibit increased pain sensitivity to contact with the vaginal vestibule as well as with vaginal penetration. The mechanism(s) responsible for this effect remains incompletely defined. Based on reports of a possible role for proteases in induction of pain, we compared levels of proteases and protease inhibitors in vaginal secretions from women with vestibulodynia and controls. Study Design Vaginal secretions from 76 women with vestibulodynia and from 41 control women were assayed by an enzyme-linked immunosorbent assay for the protease inhibitors, secretory leukocyte protease inhibitor (SLPI) and human epididymis protein-4 (HE-4), and the proteases, kallikrein-5 and cathepsins B and S. Concentrations between subjects and controls were compared and levels related to clinical and demographic variables. Results Concentrations of HE-4 and SLPI were markedly reduced in vaginal samples from women with vestibulodynia compared with controls (P ≤.006). All other compounds were similar in both groups. HE-4 (P =.0195) and SLPI (P =.0033) were lower in women with secondary, but not primary, vestibulodynia than in controls. Subjects who had constant vulvar pain had lower levels of HE-4 and SLPI than did healthy control women (P ≤.006) or women who experienced vulvar pain only during sexual intercourse (P ≤.0191). There were no associations between HE-4 or SLPI levels and event associated with symptom onset, duration of symptoms, age, number of lifetime sexual partners, or age at sex initiation. Conclusion Insufficient vaginal protease inhibitor production may contribute to increased pain sensitivity in an undefined subset of women with secondary vestibulodynia who experience constant vulvar pain.