NEUROCHEMISTRY OF GESTATION-PRODUCED ANALGESIA

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The overall objective of the proposed research is to determine the peripheral and central processes that are responsible for the elevation in the threshold for responsiveness to aversive stimuli that is observed during gestation in rats. One approach that will be utilized will be to determine the effects of mimicking and manipulating specific aspects of the pregnant condition on the pain threshold in rats. A second approach will be to determine the materal blood and cerebrospinal fluid (CSF) concentration profile of opioid peptides during gestation. The specific objectives are to (1) Determine the role, if any, of estrogen, progesterone and prolactin, alone and in combination, on the pain threshold of nonpregnant ovariectomized rats. (2) Determine whether an elevation in pain threshold is observed during pseudopregnancy, with and without deciduoma. (3) Determine if an increase in intrauterine pressure and distention is sufficient to produce an increase in pain threshold in pseudopregnant rats and ovariectomized rats subjected to hormone treatment. (4) Determine whether the presence of a developing fetus(es) is essential for the elevation in maternal pain threshold. (5) Determine the maternal blood concentration profile of B-endorphin and total opioid peptides during gestation and the post partem period. The above experiments will enable the evaluation of peripheral processes that might be involved in the pregnancy-induced elevation in pain threshold. (6) In order to assess the involvement of central mechanisms in pregnancy-induced analgesia the maternal CSF concentration profile of B-endorphin, methionine- and leucine-enkephalin and total opioids will be determined during gestation. (7) The effects of the above manipulations and simulations of pregnancy on maternal blood and CSF levels of opioid peptides will also be investigated.