Rangappa Srinath, Shankar Vijay Kumar, Jo Seongbong, Repka Michael A, Murthy S Narasimha
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Oxford, Mississippi, 38677, USA.
Institute for Drug Delivery and Biomedical Research, Bangalore, Karnataka, India.
AAPS PharmSciTech. 2021 Mar 8;22(3):95. doi: 10.1208/s12249-021-01969-0.
Vulvodynia is a chronic clinical condition associated with vulvar pain that can impair the sexual, social, and psychological life of women. There is a need for more research to develop novel strategies and therapies for the treatment of vulvodynia. Vulvodynia in experimental animal models induced via infections, allergens, and diabetes are tedious and with lessor induction rate. The objective of the study was to explore the possibility of inducing vulvodynia using a chemotherapeutic agent in a rodent model. Paclitaxel is commonly used in treating breast and ovarian cancer, whose dose-limiting side effect is peripheral neuropathy. Studies have shown that peripheral neuropathy is one of the etiologies for vulvodynia. Following paclitaxel administration (2 mg/kg i.p.), the intensity of vulvar hypersensitivity was assessed using a series of von Frey filaments (0.008 to 1 g) to ensure the induction of vulvodynia. Vulvodynia was induced from day 2 and was well sustained for 11 days. Furthermore, the induced vulvodynia was validated by investigating the potentiation of a flinch response threshold, upon topical application and systemic administration of gabapentin, a commonly used medication for treating neuropathic pain. The results demonstrate that vulvodynia was induced due to administration of paclitaxel. The fact that chemotherapeutic agent-induced vulvodynia was responsive to topical and parenterally administered gabapentin provides validity to the model. The study establishes a new, relatively simple and reliable animal model for screening drug molecules for vulvar hypersensitivity.
外阴痛是一种与外阴疼痛相关的慢性临床病症,会损害女性的性生活、社交生活和心理状态。需要开展更多研究来开发治疗外阴痛的新策略和新疗法。通过感染、过敏原和糖尿病在实验动物模型中诱发外阴痛既繁琐又诱导率较低。本研究的目的是探讨在啮齿动物模型中使用一种化疗药物诱发外阴痛的可能性。紫杉醇常用于治疗乳腺癌和卵巢癌,其剂量限制性副作用是周围神经病变。研究表明,周围神经病变是外阴痛的病因之一。给予紫杉醇(腹腔注射2mg/kg)后,使用一系列不同强度的von Frey细丝(0.008至1g)评估外阴超敏反应的强度,以确保诱发外阴痛。从第2天开始诱发外阴痛,并持续了11天。此外,通过研究在局部应用和全身给予加巴喷丁(一种常用的治疗神经性疼痛的药物)后退缩反应阈值的增强情况,验证了诱发的外阴痛。结果表明,外阴痛是由于给予紫杉醇所致。化疗药物诱发的外阴痛对局部和胃肠外给予的加巴喷丁有反应这一事实为该模型提供了有效性验证。该研究建立了一种新的、相对简单且可靠的动物模型,用于筛选针对外阴超敏反应的药物分子。