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

一夫一妻制的草原田鼠：研究社会行为和疼痛的模型

基本信息

批准号：
8823884
负责人：
THOMAS JEFFREY MARTIN
金额：
$ 23.13万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-30 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8823884
关键词：
Absence of pain sensation Address Affect Affective Animal Model Animals Behavior Behavioral Brain Stem Breeding Clinic Clinical Research Communities Dopamine Evaluation Family Female Future Genetic Genome Grooming Hamsters Health Housing Human Hypersensitivity Injury Knock-out Laboratories Laboratory Animal Models Libraries Life Ligation Literature Maintenance Measures Mechanics Microtus Midbrain structure Modeling Mus Neurobiology Operative Surgical Procedures Oxytocin Pain Pain Research Pair Bond Partner in relationship Patients Rattus Recovery Research Research Personnel Resolution Rodent Role Running Severities Sexual Partners Site Social Behavior Social Interaction Stimulus Study models Time Treatment outcome Vasopressins Vertebrates Withdrawal behavior influence behavior measurement chronic neuropathic pain chronic pain design and construction experience forest improved male multisensory mutant nerve injury neuroinflammation nonhuman primate novel offspring painful neuropathy partial recovery prairie vole pre-clinical preference productivity loss psychosocial public health relevance response sciatic nerve sex sham surgery social social attachment tool

项目摘要

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.

描述（由申请人提供）：本提案的目标是开发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。提出了两个具体目标：（1）使用超敏反应的反射性戒断措施和疼痛的情感/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）确定草原田鼠之间如何建立配对关系田鼠或这些动物中配对关系的破坏会影响神经损伤后的疼痛反应和疼痛缓解。草原田鼠在大多数脊椎动物中是独一无二的，因为它们像人类一样，形成终生的一夫一妻制关系，雄性和雌性在抚养后代方面都发挥着重要作用。临床上，与没有这种社交丰富的患者相比，与伴侣有稳定和支持性关系的慢性神经性疼痛患者的治疗结果得到改善。积极的社交互动可能减轻疼痛的机制尚未在临床前环境中得到探索，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）之间缺乏类似的社交互动。二十年来，人们一直利用草原田鼠来了解配对纽带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认识。草原田鼠基因组已完成测序，目前正在构建 BAC 文库，用于设计敲除或基因突变体，该物种将继续发展为重要的模式物种。这为疼痛研究界提供了一个机会，探索如何利用该物种来解决疼痛神经生物学问题，包括类人社会行为的影响，这是目前其他物种无法承受的。这些研究将把草原田鼠开发为临床前疼痛研究的重要工具，并促进整个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。