OPIOID PEPTIDE EFFECTS ON SPINAL LAMINA I & II NEURONS

阿片肽在应用时引起相对特异性的疼痛抑制 中线脑结构或直接应用于脊髓时。 介导这种特异性抑制的神经机制只有 部分理解。 虽然“疼痛”只能在人类身上进行研究， “伤害感受”（由组织损伤或潜在的 组织损伤刺激）可以在动物模型中进行研究。 伤害性 阿片类药物抑制神经反应， 痛苦 因此，我们建议确定是否特异性抑制 伤害性感受的直接作用是由于伤害性感受的突触后效应， 脊髓I层和II层的神经元。 为了验证这一点，我们 记录细胞外和细胞内的伤害性和非伤害性 I层和II层的神经元。 然后，我们将应用阿片类药物， 微离子电渗和微压力喷射，以确定它们是否 引起伤害感受神经元的传导性变化。 的 神经元将通过记录用辣根过氧化物酶标记 微量移液器，以确定细胞形态是否有助于 阿片类药物的作用。 在其他实验中，我们将确定是否伤害性 当阿片肽类药物作用于I和II层神经元时， 被注射到中线脑结构如导水管周围灰质。 进一步的实验旨在确定这一机制 通过使用各种特异性拮抗剂来阻断 脊髓水平的抑制。 这些实验旨在确定阿片肽是否通过 对伤害感受神经元产生特异性的突触后效应。 未来 研究可以确定不同的阿片受体亚型 介导特定的突触后效应，如果他们被发现。 最终目标是更好地了解阿片类药物的作用机制 封锁的痛苦，希望这种理解将导致 阿片类药物的生产更具选择性，成瘾性较小，并导致 更少的副作用。

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.