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.
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