Valproic acid alleviates generalized hyperalgesia in mice with induced adenomyosis
Tóm tắt
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.
Từ khóa
Tài liệu tham khảo
Council NR, 1996, Guide for the Care and Use of Laboratory Animals
Le Bars D, 2001, Animal models of nociception, Pharmacol Rev, 53, 597
Kooperberg C, 1997, Polychotomous regression, J Am Statist Assoc, 92, 117, 10.1080/01621459.1997.10473608
Team RDC, 2010, R: A Language and Environment for Statistical Computing
Dong XF, 2007, Histone deacetylase inhibitor valproic acid inhibits proliferation and induces apoptosis in KM3 cells via downregulating VEGF receptor, Neuro Endocrinol Lett, 28, 775
Kogan EA, 2010, [The morphological and immunohiochemical features of foci of adenomyosis: in its concurrence with endometrial adenocarcinoma], Arkh Patol, 72, 7
Mori T, 1998, Animal model of uterine adenomyosis: induction of the lesion in rats by ectopic pituitary isografting, Lab Anim Sci, 48, 64
IgarashiM YokotaY IgarashiT IgarashiS AbeY LiangS.Novel transvaginal echo‐guided injection treatment for adenomyosis vaginal and deep endometriosis and ovarian endometriosis with a danazol 3‐ethyl pyridine or valproic acid solution. The First Asian Conference on Endometriosis Shanghai 2010.