ROLE OF ESTROGEN AND PROGESTERONE IN SCI PAIN

雌激素和孕酮在 SCI 疼痛中的作用

• 批准号: 7959681
• 负责人: CHARLES H. HUBSCHER
• 金额: $ 25.03万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959681
• 关键词: Animals; Behavioral; Brain Stem; Chronic; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Estrogens; Female; Funding; Grant; Hormonal; Human; Information Centers; Injury; Institution; Lead; Measures; Neurons; Operative Surgical Procedures; Ovarian hormone; Pain; Pain Threshold; Pathway interactions; Pattern; Pharmacotherapy; Play; Process; Progesterone; Rattus; Relative (related person); Research; Research Personnel; Resources; Role; Source; Spinal cord injury; Spinal cord injury patients; Thalamic structure; Therapeutic; Touch sensation; United States National Institutes of Health; Variant; allodynia; central pain; clinically relevant; in vivo Model; interdisciplinary approach; male; neuromechanism; prevent; repaired; response; spinal cord injury pain

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chronic central pain develops in the majority of spinal cord injury (SCI) patients following complete and partial injuries, including at level allodynia (pain to touch in dermatomes at and just above the level of injury). Using a recently developed electrophysiological rat model (in vivo) for investigating the effects of chronic SCI on responses in supraspinal neurons, new data from our lab was obtained which indicates that the development of at level allodynia is dramatically reduced after SCI in female rats with normal hormonal cycles compared to males/ovariectomized females. This raises the possibility that progesterone and/or estrogen could play therapeutic roles for SCI-induced pain. We also have evidence supporting the hypothesis that at level allodynia, if and when it develops, may result from damage to descending pathways in the dorsolateral quadrant in combination with sparing of at least a portion of ascending tract(s) in the ventrolateral quadrant that transmit, to higher centers, the information from dermatomes just above the level of injury. Moreover, preliminary data indicate that the allodynia, when it develops, may be exacerbated by circulating progesterone and/or estrogen, which is clearly seen in the responsiveness of brainstem neurons. This exacerbation is consistent with findings for numerous conditions with cycle related changes in pain thresholds in humans. Thus, the development and perpetuation of at level allodynia will be examined relative to experimental variations of hormonal status and variations in specific patterns of damage/sparing. The underlying mechanism may include changes in the responses of neurons in the thalamus (an important region involved in the processing of inputs that ultimately lead to pain), which will be compared to the concomitant behavioral signs that accompany these changes (i.e., allodynia). Thus, a unique feature of this proposal is the multidisciplinary approach that is taken, i.e., using electrophysiological, behavioral and anatomical measures for each animal. The proposed research will examine the underlying mechanisms related to ovarian hormones that prevent the development and contribute to the perpetuation of this clinically-relevant at level allodynia. Therefore, these studies will lead to a better understanding of the neural mechanisms underlying SCI pain and will identify ovarian hormones as targets that can readily be modulated to prevent and treat SCI-related pain. This is very important, since current drug therapies and surgical interventions are inadequate.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 完全和部分损伤后，大多数脊髓损伤（SCI）患者（包括处于水平的异常性）患者（SCI）患者（SCI）患者（SCI）患者（在损伤水平上的皮肤皮肤上接触疼痛）会出现慢性中心疼痛。 使用最近开发的电生理大鼠模型（体内），用于研究慢性SCI对上植物神经元反应的影响，获得了我们实验室的新数据，这表明与雄性/卵巢症患者相比，女性大鼠的SCI在SCI中大大降低了AT水平的AT水平同性恋性nia症的发展。 这增加了孕酮和/或雌激素可以扮演Sci诱发的疼痛的治疗作用的可能性。 我们还有证据支持以下假设：在水平异常症中，如果和何时发育，可能是由于对背外侧象限下降途径的损害，与至少部分上升象限的上升象限至少相结合，从而传播到高等中心的信息，从上面的较高中心受到损害。 此外，初步数据表明，当孕激素发育时，可能会因循环孕酮和/或雌激素而加剧，这在脑干神经元的反应性中可以清楚地看到。 这种加剧与人类疼痛阈值相关的众多条件的发现是一致的。因此，将研究与激素状态的实验变化和特定损害/保留模式的变化相对于AT水平异常症的发展和延续。 基本机制可能包括丘脑中神经元的反应的变化（涉及最终导致疼痛的输入的重要区域），这将与这些变化伴随的行为迹象（即同种症）进行比较。 因此，该提案的独特特征是采用的多学科方法，即使用每种动物的电生理，行为和解剖学测量方法。 拟议的研究将研究与卵巢激素有关的潜在机制，这些机制阻止了发展的发展，并有助于该临床上的临床水平与高度同胞性疾病的延续。 因此，这些研究将使对SCI疼痛的神经机制有更好的了解，并将卵巢激素视为可以轻松调节和治疗与科幻相关的疼痛的靶标。 这非常重要，因为当前的药物疗法和手术干预措施不足。