REGULATION OF AFFERENT NEUROTRANSMITTER RELEASE

Project: Research project

Description

The overall goal of this work is to detemrine which neurotransmitters are
important in regulating nociception at the level of the spinal cord and the
mechanism of the regulations. Evidence from the literature shows that
norepinephrine, opioids, and gamma aminobutyric acid are involved in
regulation of nociception at the level of the dorsal horn of the spinal
cord. Although the mechanisms of this antinociception remain unknown,
preliminary evidence suggests that norepinephrine and morphine may act in
part by inhibiting the release of the putative afferent neurotransmitter
substance P. The purpose of the proposed studies is to determine if
norepinephrine, opioid agonists, and gamma-aminobutyric acid inhibit the
release of the afferent nociceptive neurotransmitters, substance P, and
somatostatin. Peptide release will be induced in superfused rat spinal cord slices using
high extracellular potassium and veratridine. Substance P and somatostatin
in the perfusate will be measured by radioimmunoassay. Dose-response
relationships for norepinephrine, opioids, and gamma aminobutyric acid
agonists will be determined. Specific receptor antagonists will be used to
determine which receptors mediate any observed inhibition of transmitter
release. Studies will also be performed in spinal cord slices taken from
rats made tolerant to analgesic doses of morphine to determine if tolerance
develops to the inhibition of peptide release. Finally, studies will be
performed in rats pretreated with the neurotoxin, capsaicin, to determine
if the observed effects on peptide release are occurring on primary
afferent neurons. Understanding neurotransmitter interactions at the level of the dorsal horn
of the spinal cord is critical in determining what mechanisms regulate
nociception and ultimately in designing clinical strategies for the
management of pain. The proposed experiments will provide new information
regarding the neurochemistry of regulation of afferent neurotransmitter
release and will complement previous electrophysiological and
immunohistochemical studies.
StatusFinished
Effective start/end date4/1/863/31/90

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Neurotransmitter Agents
Spinal Cord
Opioid Analgesics
Nociception
Substance P
Morphine
Peptides
Norepinephrine
Veratridine
GABA Agonists
Neurochemistry
Capsaicin
Neurotoxins
gamma-Aminobutyric Acid
Radioimmunoassay
Analgesics
Potassium
Neurons
Pain
Inhibition (Psychology)

ASJC

  • Medicine(all)
  • Neuroscience(all)