The Monogamous Prairie Vole: A Model for the Study of Social Behavior and Pain

描述(申请人提供)：这项提议的目标是发展一夫一妻制的草原田鼠作为临床前疼痛研究的新型实验动物模型。我们提出了两个具体的目标：(1)使用高敏感性的反射性撤退措施和疼痛的情感/动机成分的非反射性措施来确定草原田鼠对神经损伤的反应，以及(2)确定草原田鼠之间的配对结合或这些动物的配对结合的中断如何影响神经损伤后的疼痛反应和疼痛的解决。草原田鼠在大多数脊椎动物物种中是独一无二的，因为像人类一样，它们形成终身一夫一妻制的伴侣关系，雄性和雌性在抚养后代方面都扮演着重要的角色。临床上，与伴侣保持稳定和支持性关系的慢性神经病理性疼痛患者被证明比那些没有这种社交丰富的患者有更好的治疗结果。积极的社会互动可以减轻疼痛的机制尚未在临床前环境中探索，部分原因是人类与典型的实验动物模型(如小鼠和大鼠，甚至非人类灵长类动物)之间缺乏类似的社会互动。二十年来，草原田鼠一直被用来了解配对纽带形成和社会互动的神经生物学，现在人们认识到催产素、加压素和多巴胺在这些行为中的重要作用。草原田鼠的基因组已经测序，目前正在构建BAC文库，用于设计基因敲除或遗传突变，该物种将继续被发展为重要的模式物种。这为疼痛研究界提供了一个机会，以探索如何利用该物种来研究疼痛神经生物学，包括类似人类的社会行为的影响，这是其他物种目前无法承受的。这些研究将使草原田鼠成为临床前疼痛研究的重要工具，并促进广大草原田鼠研究界对疼痛如何影响这些动物的社会行为的理解。

DESCRIPTION (provided by applicant): The objectives of this proposal are to develop the monogamous prairie vole as a novel laboratory animal model for preclinical pain research. Two specific aims are proposed: (1) determine the response of prairie voles to nerve injury using both reflexive withdrawal measures of hypersensitivity and non-reflexive measures of the affective/motivational components of pain, and (2) determine how pair-bonding between prairie voles or disruption of pair bonds in these animals affects pain responses and resolution of pain after nerve injury. Prairie voles are unique among most vertebrate species in that, like humans, they form lifelong monogamous pair bonds with both the male and female undertaking significant roles in raising offspring. Clinically, patients with chronic neuropathic pain that reprt stable and supportive relationships with a partner are shown to have improved treatment outcomes than those without such social enrichment. The mechanisms by which positive social interaction may mitigate pain have not been explored in a preclinical setting, in part due to the lack of similar social interactions between humans and typical laboratory animal models such as mice and rats, or even non-human primates. The prairie vole has been utilized for two decades to understand the neurobiology of pair bond formation and social interaction, and the prominent role of oxytocin, vasopressin, and dopamine in these behaviors are now appreciated. The prairie vole genome has been sequenced and BAC libraries are currently being constructed for design of knockouts or genetic mutants and this species will continue to be developed as an important model species. This provides the pain research community with an opportunity to explore ways in which this species can be utilized to address pain neurobiology, including the influence of human-like social behaviors, which no other species can presently afford. These studies will develop the prairie vole as an important tool for preclinical pain research, as well a advance the understanding of how pain influences social behavior in these animals for the prairie vole research community at large.