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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA004420-03
Application #
3210044
Study Section
Pharmacology I Research Subcommittee (DABR)
Project Start
1987-04-01
Project End
1992-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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