The overall objective of the research described in this proposal is to elucidate the mechanism of action of morphine and other opiates.
The specific aims of the work proposed in this application are: one, to continue to test our hypothesis that the release of endogenous opiates is an important step in the antinociceptive action of morphine. The data which we have generated thus far indicates that there is an increase in the quantity of known endogenous opiates including met- and leu-enkephalin, Beta-endorphin and dynorphin in dog CSF following an acute injection of an antinociceptive dose (10 mg/kg, s.c.) of morphine. We have also presented evidence that this dose of morphine causes an increase in yet to be identified peptides in CSF which also have opioid activity. Our data also suggests that there is at least one nonpeptide with opioid activity in CSF after morphine. This opioid activity is not due to the presence of morphine in the CSF. Secondly, we propose to study the antinociceptive activity of calcitonin and other endogenous peptides not classified as opiates. Another aspect of these studies will be an investigation of the effects of calcitonin and other endogenous peptides on morphine's actions. Our third specific aim is to elucidate the role of endogenous opioid peptides in sudden infant death syndrome. Preliminary results show that the level of immunoreactivity to Beta-endorphin antibody is significantly higher in babies whose siblings have died of sudden infant death syndrome than in infants of the same age who have had spinal taps for other reasons. The basic information generated from these projects will expand our understanding of pain and its alleviation by opiates, the role of endogenous opiates in normal and abnormal breathing, and the role of peptides not considered opioid as neuromodulators in the actions of endogenous and exogenous opiates.
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