title: Valproic acid alleviates generalized hyperalgesia in mice with induced adenomyosis.
abstract: Emerging evidence suggests that adenomyosis, like endometriosis, may also be an epigenetic disease. In this study, we evaluated the effect of valproic acid (VPA) in ICR mice with adenomyosis, induced by neonatal dosing with tamoxifen. For all mice, we evaluated the bodyweight and the response to thermal stimuli by hotplate and tail-flick tests 4, 8, and 12 weeks after dosing, respectively, and then treated mice with low- and high-dose of VPA, progesterone (P4), P4 + VPA, or vehicle only. Three weeks after treatment, both bodyweight and thermal response tests were evaluated again before sacrifice, and the depth of myometrial infiltration was evaluated. We found that: (i) the induction of adenomyosis resulted in progressive generalized hyperalgesia as measured by hotplate and tail-flick tests, along with decreased bodyweight; (ii) treatment with VPA, P4, or a combination was efficacious in improving generalized hyperalgesia; and (iii) drug treatment appeared to reduce the myometrial infiltration, but the difference did not reach statistical significance. Thus, VPA seems to be a promising therapeutics for treating adenomyosis, as reported recently in some case series in humans.
authors.affiliation: Shanghai Obstetrics and Gynecology Hospital, Shanghai College of Medicine, Fudan University, Shanghai, China.
authors.forename: Xishi
authors.initials: X
authors.lastname: Liu
authors.forename: Sun-Wei
authors.initials: SW
authors.lastname: Guo
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D004715:Endometriosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008813:Mice, Inbred ICR; D009215:Myometrium / Q000187:drug effects / Q000473:pathology; D011897:Random Allocation; D013629:Tamoxifen / Q000633:toxicity; D015149:Tocolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014635:Valproic Acid / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D018712:Analgesics, Non-Narcotic; D015149:Tocolytic Agents; D013629:Tamoxifen; D014635:Valproic Acid