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

描述（由申请人提供）：本提案的目的是开发一夫一妻制草原田鼠作为临床前疼痛研究的新型实验室动物模型。提出了两个具体的目标：（1）确定草原田鼠神经损伤的反应，同时使用反射性撤回措施的超敏反应和非反射性措施的情感/动机成分的疼痛，和（2）确定如何草原田鼠之间的配对债券或破坏对债券在这些动物影响疼痛反应和神经损伤后的疼痛的解决。草原田鼠在大多数脊椎动物物种中是独一无二的，就像人类一样，它们形成终身一夫一妻制的配偶关系，雄性和雌性都在抚养后代中扮演重要角色。在临床上，慢性神经性疼痛的患者，代表稳定和支持的关系与合作伙伴被证明有改善的治疗结果比那些没有这样的社会丰富。积极的社会互动可能减轻疼痛的机制尚未在临床前环境中探索，部分原因是人类和典型的实验室动物模型（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键形成和社会互动的神经生物学，催产素，加压素和多巴胺在这些行为中的重要作用现在得到了赞赏。草原田鼠的基因组已经测序，目前正在构建BAC文库，用于基因敲除或遗传突变体的设计，该物种将继续作为重要的模式物种进行开发。这为疼痛研究界提供了一个机会，探索如何利用这种物种来解决疼痛神经生物学问题，包括类似人类的社会行为的影响，这是目前其他物种无法承受的。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.