ANALGESIA PRODUCED BY BIRTH CANAL STIMULATION

我们的目标是确定出生时释放的神经递质(S) 管内机械刺激介导(S)强镇痛触发 通过这种感官刺激，通过以下方式从药理上增强这种止痛 抑制神经递质的酶促分解(S)，并测定 这些酶抑制剂在自然状态下是否增强了止痛作用 分娩。 具体目标是： 1)确定脑啡肽酶抑制剂、硫吗啡和 蛋白水解酶抑制剂，亮氨酸，直接注射到脊髓 (鞘内)通过慢性导管，加强和/或延长 由人工产道机械刺激产生的止痛，以及 阿片类拮抗剂纳洛酮是否拮抗这种作用。这 将提供证据证明阿片剂和/或 非阿片类止痛产生系统被这种酶增强 抑制剂。 2)确定相同的药理治疗是否加强 和/或延长自然分娩期间的止痛，这 通常为产道(如宫颈)提供机械刺激 他们是天生的。 3)用放射免疫法测定所选神经肽的水平。 (如血管活性肠肽和甲硫氨酸脑啡肽) 脊髓和脊髓节段的匀浆，对 止痛-产生产道刺激。这将提供证据作为 产生镇痛作用的特定神经肽是否在体内释放 脊髓对感觉刺激的反应类似于 正常发生在分娩期间。 最终的目标是在药理学和/或神经学上利用， 这种强大的止痛触发自然感觉系统用于控制 人类的痛苦。

Our objectives are to identify the neurotransmitter(s) released by birth canal mechanostimulation that mediate(s) the powerful analgesia triggered by this sensory stimulus, to augment this analgesia pharmacologically by inhibiting enzymatic breakdown of the neurotransmitter(s), and to determine whether these enqyme-inhibitors augment analgesia during natural parturition. The specific aims are: 1) to determine whether the enkephalinase inhibitor, thiorphan, and the protease inhibitor, leupeptin, injected directly to the spinal cord (intrathecally) via chronic catheter, intensify and/or prolong the analgesia produced by artificial birth canal mechano-stimulation, and whether the opiate antagonist, naloxone, antagonizes this effect. This will provide evidence as to whether the activity of opiate and/or non-opiate analgesia-producing systems are potentiated by the enzyme inhibitors. 2) to determine whether the same pharmacological treatments intensify and/or prolong analgesia during the natural delivery of fetuses, which normally provide mechano-stimulation of the birth canal (e.g. cervix) as they are born. 3) to quantify, by radioimmunoassay, the levels of selected neuropeptides (e.g. vasoactive intestinal peptide and met-enkephalin) in superfusates of the spinal cord and homogenates of spinal cord segments, in response to analgesia-producing birth canal stimulation. This will provide evidence as to whether specific neuropeptides that produce analgesia are released in the spinal cord in response to sensory stimulation similar to that occurring normally during parturition. The ultimate goal is to utilize, pharmacologically and/or neurologically, this powerful analgesia-triggering natural sensory system for the control of pain in humans.