OPIOID PEPTIDE EFFECTS ON SPINAL LAMINA I & II NEURONS

阿片肽在应用时对疼痛有相对特异性的抑制作用 中线大脑结构，或直接应用于脊髓。 调节这种特定抑制的神经机制只是 部分地理解了。虽然“疼痛”只能在人类身上研究， “伤害感”(由组织损伤或潜在的神经反应所激活) 组织损伤刺激)可以在动物模型中进行研究。伤害性的 神经反应被阿片类药物抑制，与抑制 疼痛。因此，我们建议确定特定的抑制是否 伤害性感觉的产生是由于突触后对伤害性感觉的直接影响 脊髓I、II板层的神经元。为了测试这一点，我们将 伤害性和非伤害性的细胞外和细胞内记录 板层I和II中的神经元。然后我们将通过 微离子导入和微压喷射以确定它们是否 引起伤害感受性神经元的电导变化。这个 通过记录，神经元将被标记辣根过氧化物酶 微吸管以确定细胞形态是否有助于 阿片类药物效应。在其他实验中，我们将确定伤害性感受是否 阿片肽对I层和II层神经元的特异性抑制作用 被注入中线大脑结构，如中脑导水管周围灰质。 进一步的实验被设计来确定这一机制。 通过使用不同的特异性拮抗剂来阻断 脊椎水平的抑制。 这些实验旨在确定阿片肽是否通过 对伤害性神经元产生特定的突触后效应。未来 研究可以确定各种阿片受体亚型中的哪一种 调节特定的突触后效应，如果发现它们的话。 最终目标是更好地理解阿片类药物的作用机制。 封锁痛苦，希望这种理解将导致 阿片类药物的生产具有更高的选择性，更少的成瘾性，并导致 副作用更少。

Opioid peptides cause relatively specific inhibition of pain when applied to midline brain structures or when applied directly to the spinal cord. The neural mechanisms which mediate this specific inhibition are only partially understood. While "pain" can be studied only in humans, "nociception" (neural responses activated by tissue damaging or potentially tissue damaging stimuli) can be studied in animal models. Nociceptive neural responses are inhibited by opioids paralleling the inhibition of pain. We, therefore, propose to determine whether the specific inhibition of nociception is due to direct, postsynaptic effects on nociceptive neurons in laminae I and II of the spinal cord. To test this, we will record extra- and intracellularly from both nociceptive and non-nociceptive neurons in laminae I and II. We will then apply opioids via micro-iontophoresis and micro-pressure ejection to determine whether they cause conductance changes specifically in the nociceptive neurons. The neurons will be labeled with horseradish peroxidase via the recording micropipette to determine whether cellular morphology contributes to the opioid effects. In other experiments we will determine whether nociceptive neurons in laminae I and II are specifically inhibited when opioid peptides are injected into midline brain structures such as periaqueductal gray. Further experiments are designed to determine the mechanisms of this descending inhibition by using various specific antagonists to block the inhibition at the spinal level. These experiments are designed to determine whether opioid peptides act by producing postsynaptic effects specifically on nociceptive neurons. Future studies could determine which of the various opiate receptor subtypes mediate specific postsynaptic effects, if they are found. The ultimate goal is a better understanding of the mechanism of the opioid blockade of pain with the hope that this understanding will lead to the production of opioids which are more selective, less addicting, and lead to fewer side effects.