Long term hyperalgesia mediated by spinal dorsal horn

脊髓背角介导的长期痛觉过敏

• 批准号: 6470111
• 负责人: ALAN R LIGHT
• 金额: $ 18.6万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6470111
• 关键词: behavior test; behavioral habituation /sensitization; chronic pain; dorsal horn; genetically modified animals; glia; hyperalgesia; immunocytochemistry; laboratory mouse; laboratory rat; nerve injury; nociceptors; pain threshold

The enhancement of pain following injury occurs acutely within a few minutes, and can last for several days or weeks. In some cases, the enhance pain can last indefinitely, either because the injured cannot be repaired, or because of some unknown mechanism that may not be related to peripheral injury. In these cases, the pain is defined as "chronic pain." It has been proposed that long-term exposure to painful stimuli can cause profound changes in the central nervous system that are very difficult to alter and are the cause of chronic pain. Chronic pain has proven to be extremely debilitating for affected individuals, and has been refractory to most treatments. We hypothesize that one of the CNS locations in which pain transmission is altered by persistent nociceptive inputs is the spinal cord. Just as a number of peripheral events contribute to short-term sensitization of peripheral nociceptors (see Projects 2 and 3), it is likely that long-term spinal cord sensitization of peripheral nociceptors (see Projects 2 and 3), it is likely that long-term spinal cord sensitization requires a combination of factors involving damaged peripheral tissue, afferent traffic from that tissue, and spinal responses to the peripheral injury. We propose that understanding, long-term spinal sensitization requires systematic manipulation and evaluation of combinations of peripheral, afferent and central effects that have been implicated individually as contributors to persistent pain. Once these factors are understood, rational treatments can be developed. The specific aims for the next 5 years are to determine: 1. the contribution of primary afferent firing in our present model of long- term hyperalgesia. 2. whether blockade of afferent activity, axonal transport of peripheral nerve ending destruction a) affects the glial activation and allodynia/hyperalgesia produced by peripheral injection of formalin, and/or b) produces glial activation and allodynia/hyperalgesia without peripheral tissue damage. 3 whether activation of spinal cord glial cells (astrocytes and microglial cells) is involved in short- and long-term hyperalgesia. 4. some of the potential mediators that activate astrocytes and microglia and induce long-term hyperalgesia in our formalin model. Combinations of single afferent recording, behavior, and immunohistochemistry will be used on rats and transgenic mice to accomplish these aims.

受伤后疼痛的增强在几分钟内急性发生，并且可以持续几天或几周。在某些情况下，增强疼痛可以无限期地持续，因为受伤的人无法修复，或者由于某些可能与周围损伤无关的未知机制。在这些情况下，疼痛被定义为“慢性疼痛”。有人提出，长期暴露于疼痛刺激会导致中枢神经系统的深刻变化，这很难改变，并且是慢性疼痛的原因。事实证明，慢性疼痛对受影响的个体来说是极度衰弱的，并且对大多数治疗感到难治。我们假设脊髓是持续的伤害感受输入改变疼痛传播的CNS位置之一。就像许多周围事件有助于外周伤害感受器的短期敏化（请参阅项目2和3）一样，长期的外周伤害感受器的长期脊髓脊髓敏感性（请参阅项目2和3）（参见项目2和3），长期的脊髓敏感性可能需要使散布的因素与受损的范围伴随组织，并涉及周围的杂物，并涉及损害的周围，并伴随着附近的组织，附近的组织和附加的杂物组织伴随着附近的杂物组织，并需要伴随组织的交通量。 受伤。我们建议理解，长期的脊柱敏化需要系统地操纵和评估外围，传入和中心效应的组合，这些效应被单独牵涉到持续性疼痛的贡献者。一旦理解了这些因素，就可以开发理性治疗。未来5年的具体目的是确定：1​​。在我们目前的长期杀伤性模型中，主要传入射击的贡献。 2。是否阻塞传入活性，周围神经结束破坏的轴突转运a）会影响神经胶质激活和通过外周向福尔马林注射产生的胶质激活和异常性nia/痛觉过敏和/或b）产生神经胶质激活和异常性nia/hypergusia而没有外周组织损害。 3脊髓神经胶质细胞（星形胶质细胞和小胶质细胞）的激活是否参与短期和长期痛觉过敏。 4。在我们的福尔马林模型中激活星形胶质细胞和小胶质细胞并诱导长期痛觉过敏的一些潜在介体。单个传入记录，行为和免疫组织化学的组合将用于大鼠和转基因小鼠，以实现这些目标。