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: 7381136
• 负责人: CHARLES H. HUBSCHER
• 金额: $ 24.63万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381136
• 关键词: ROLE; ESTROGEN; PROGESTERONE; SCI; 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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。慢性中枢性疼痛在大多数脊髓损伤（SCI）患者中在完全和部分损伤后发展，包括在水平异常性疼痛（在损伤水平处和刚好高于损伤水平的皮区中触摸疼痛）。使用最近开发的电生理大鼠模型（体内）研究慢性SCI对脊髓上神经元反应的影响，从我们的实验室获得的新数据表明，与雄性/卵巢切除雌性大鼠相比，SCI后激素周期正常的雌性大鼠的水平异常性疼痛的发生显著减少。这增加了孕激素和/或雌激素可能对SCI诱导的疼痛起治疗作用的可能性。我们也有证据支持这一假设，即在水平上，如果发生异常性疼痛，可能是由于背外侧象限的下行通路受损，同时腹外侧象限的至少一部分上行通路保留，这些上行通路将来自损伤水平上方皮节的信息传递到更高的中枢。此外，初步数据表明，异常性疼痛，当它的发展，可能会加剧循环孕酮和/或雌激素，这是清楚地看到在脑干神经元的反应。这种恶化与人类疼痛阈值周期相关变化的许多疾病的发现一致。因此，在水平异常性疼痛的发展和延续将检查相对于激素状态的实验变化和损伤/保留的特定模式的变化。潜在的机制可能包括丘脑（参与最终导致疼痛的输入处理的重要区域）神经元反应的变化，将其与伴随这些变化的伴随行为体征（即，异常性疼痛）。因此，本提案的一个独特之处是采取了多学科办法，即，对每只动物进行电生理学、行为学和解剖学测量。拟议的研究将研究与卵巢激素相关的潜在机制，这些机制阻止了这种临床相关的异常性疼痛的发展并有助于其持续存在。因此，这些研究将有助于更好地了解SCI疼痛的神经机制，并将确定卵巢激素作为可以容易地调节以预防和治疗SCI相关疼痛的靶点。这是非常重要的，因为目前的药物治疗和外科手术是不够的。