PAIN REDUCTION BY GRAFTS OF CHROMAFFIN CELL DERIVATIVES

Project: Research project

Description

Chromaffin cells and their derivatives contain and release several
neuroactive substances, including catecholamines and opioid
peptides. The transplantation of chromaffin cells into CNS pain
modulatory regions sensitive to these agents may provide a
permanent and locally available source of neuroactive substances
for the relief of pain. The goal of the proposed program is to
assess the potential for neural transplants to provide a new
therapeutic approach to the problem of intractable pain. Transplant tissue for these studies will include rat adrenal
medullary tissue, isolated bovine chromaffin cells, PC12 cells, and
derivatives of these using pharmacological and molecular
manipulations. These graft tissues will be placed in the midbrain
periaqueductal gray or the dorsal spinal cord, and behavioral,
biochemical, and morphological changes will be monitored over
time. To assess the potential for therapeutic use, both acute and
chronic pain models will be used. Pharamacological studies will
include responses to cell surface receptor agonists and
antagonists, as well as the role of released catecholamines and
opioid peptides from transplanted cells. In addition,
enkephalinase inhibitors may prolong alterations in pain
sensitivity. Tolerance and tachphylaxis will also be assessed. Biochemical levels of neuroactive substances may be altered when
cells are transplanted to the new CNS environment. Biochemical
changes in host and grant tissue will be determined using
radioimmunoassays and HPLC. Furthermore, in the new CNS
environment, transplanted cells may differentiate
morphologically, and form synaptic or non-synaptic relationships
with the host CNS. Host-graft relationship will be studied
morphologically using electron microscopy and
immunocytochemistry. Both biochemical and morphological changes may be induced by
environmental manipulation with agents such as nerve growth
factor or butyric acid. Effects of these agents on host and graft
tissue will also be determined. In addition, it may be possible to
increase the level of opioid peptide production in cells using
molecular manipulations. A goal of this proposal is to develop a
cell line for transplantation that will produce increased levels of
opoid peptides using gene transfer techniques.
StatusFinished
Effective start/end date7/1/878/31/01

Funding

  • National Institutes of Health: $100,146.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $50,000.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Chromaffin Cells
Transplants
Pain
Transplantation
Opioid Peptides
Catecholamines
Acute Pain
Peptides
Subarachnoid Space
Spinal Cord
Neprilysin
Intractable Pain
Gene Transfer Techniques
Butyric Acid
Organized Financing
PC12 Cells
Cell Surface Receptors
Therapeutic Uses
Safety
Allografts

ASJC

  • Medicine(all)
  • Neuroscience(all)