DESCENDING MODULATION OF SPINAL SUBSTANTIA GELATINOSA

急性和慢性疼痛仍然是最常见的主诉。 医生被要求进行治疗。虽然急性疼痛可以在 大多数情况下，目前困难的案件中的强烈痛苦 治疗需要不断探索新的治疗方法 副作用更少，成瘾风险更小。慢性疼痛继续存在 每年直接花费600多亿美元，很难处理 治疗这种疾病。3.这些问题源于我们的不完整 对急性疼痛的调制及其机制的认识 到慢性疼痛。为了合理开发新的治疗方法 对于急慢性疼痛的治疗，更多的是必不可少的 彻底了解突触、细胞和分子 伤害性信息的传递机制是 边缘带(I层)和胶状质的改变 (椎板II)。这是我们的长期目标。 求婚。建议的下一个五年计划的具体目标是： 1.研究下行输入对大鼠脑内突触整合的调节作用 活体记录到板层I、II神经元。 2.测定红曲霉的生理和形态特性 体外记录的I、II板层抑制性中间神经元 已在活体内确认。 3.分析即刻早期基因的参与情况。 伤害性刺激对伤害性感受器长期调制的影响 行为。 这些特定的目标将通过使用大鼠的体外和 活体全细胞膜片钳技术。录音将会是 与细胞内标记相结合，使神经元及其 树枝和轴突可用光镜和电子显微镜观察。 显微镜。推测的神经递质将使用以下方法进行评估 免疫细胞化学技术。反义寡核苷酸策略 将与有害反应的行为测量相结合 刺激大鼠以确定即刻早期基因在脑出血中的重要性 调节疼痛行为的长期变化。

Acute and chronic pain continue to be the most common complaints that physicians are asked to treat. While acute pain can be managed in most cases, the intense suffering in the cases that are currently difficult to treat demands a constant search for new methods of treatment with fewer side effects and risk of addiction. Chronic pain continues to be very difficult to treat with over $60 billion annually directly spent on treating this disorder. There problems stems from our incomplete understanding of the modulation of acute pain and mechanisms leading to chronic pain. In order for rational development of new therapies for the treatment of acute and chronic pain, it is essential to more thoroughly understand the synaptic, cellular, and molecular mechanisms by which transmission of nociceptive information is modified in the marginal zone (lamina I) and substantia gelatinosa (lamina II) of the spinal cord. This is long-term objective of this proposal. The suggested specific aims for the next 5-year period are: 1. To study how descending inputs modulate synaptic integration of laminae I and II neurons recorded in vivo. 2. To determine the physiological and morphological properties of inhibitory interneurons in laminae I and II recorded in vitro and confirmed in vivo. 3. To analyze the involvement of immediate early genes evoked by noxious stimulation on the long-term modulation of nociceptive behavior. These specific aims will be accomplished by using rats for in vitro and in vivo whole-cell patch clamping techniques. Recordings will be combined with intracellular labeling so that the neuron and its dendritic and axonal arbor can be examined with the light and electron microscope. Putative neurotransmitters will be assessed using immunocytochemical techniques. Antisense oligonucleotide strategies will be combined with behavioral measurement of responses to noxious stimuli in rats to determine the importance of immediate early genes in mediating long-term changes in pain behavior.