DESCENDING MODULATION OF SPINAL SUBSTANTIA GELATINOSA

急性和慢性疼痛仍然是最常见的投诉 医生被要求治疗。虽然急性疼痛可以在 在大多数情况下，在目前困难的情况下， 治疗需要不断寻找新的治疗方法， 更少的副作用和成瘾风险。慢性疼痛仍然是 每年直接花费超过600亿美元用于治疗， 治疗这种疾病。 这些问题源于我们的不完整 了解急性疼痛的调制和机制， 慢性疼痛。 为了合理开发新疗法 对于急性和慢性疼痛的治疗， 彻底了解突触，细胞和分子 伤害性信息传递的机制 边缘区（I层）和胶状质发生改变 （椎板II）的脊髓。 这是一个长期的目标 提议 建议的下一个五年期具体目标是： 1.为了研究下行输入如何调节突触整合， I和II层神经元 记录在体内。 2.为了确定生理和形态学特性， 抑制性中间神经元 体外记录的I和II层， 在体内证实。 3.为了分析直接早期基因的参与， 伤害性刺激 伤害性感受的长时程调制 行为 这些具体目标将通过使用大鼠进行体外和体外培养来实现。 体内全细胞膜片钳技术。 记录将 与细胞内标记结合， 树突和轴突乔木可以检查与光和电子 显微镜 假定的神经递质将使用 免疫细胞化学技术。 反义寡核苷酸策略 将结合对有害物质反应的行为测量， 刺激大鼠，以确定立即早期基因在 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.