Project: Research project

Project Details


DESCRIPTION: (Applicant's Abstract)

The transplantation of cells or tissue into the CNS is a potential means of
achieving sustained delivery of naturally derived pharmacologically active
substances for the alleviation of chronic disorders. Work in our laboratory
has demonstrated that adrenal medullary or chromaffin cell transplants in
the spinal subarachnoid space can alleviate pain symptoms in several animal
models. This most likely involves the release of pain-reducing neuroactive
substances, such as opioid peptides and catecholamines, from the
transplanted cells. A significant advantage of the transplant approach for
the chronic pain patient is the potential ability to provide a continually
renewable source of analgesic agents, reducing or eliminating the need for
repeated narcotic administration. As a result of promising findings in
animal studies, clinical studies have been initiated at several centers in
patients with cancer pain, with encouraging results. The goals of the
proposed studies are to understand the mechanisms, long-term consequences,
and potential limitations of these transplants in the CNS. Pharmacologic
and biochemical analyses will be done in order to determine transplant
interactions with host spinal receptors, the contribution of opioid and
other neuropeptides to pain reduction, and tolerance and cross-tolerance to
traditional pharmacotherapies. The mechanisms of the transplants in
reducing both acute and chronic pain processes may be distinct, and will be
evaluated using selective nociceptor activation and acute and chronic pain
models. It is thought that chronic pain such as that consequent to
peripheral nerve injury or inflammation results from a cascade of
neuropathological events leading to persistent hyperexcitability, including
activation of NMDA receptors and the production of nitric oxide and cyclic
GMP. Clinically, in spite of advances in pain management, some of the most
debilitating disorders are those associated with peripheral or central nerve
lesions and chronic inflammation, and are poorly or inadequately controlled
by traditional pharmacotherapies. Recent studies in our laboratory have
suggested that adrenal medullary or chromaffin cell transplants can
alleviate symptoms of chronic pain due to peripheral nerve injury and
inflammation, and may do so via intervening in the NMDA/NO cascade. Thus,
if successful, the findings from these studies could lead to a novel
approach in the long term therapeutic intervention for alleviation of
chronic pain syndromes, particularly those refractory to traditional
pharmacotherapies, who would benefit greatly by improved quality of life
free from pain.
Effective start/end date4/10/971/31/04


  • National Institute on Drug Abuse: $254,292.00
  • National Institute on Drug Abuse
  • National Institute on Drug Abuse: $246,888.00
  • National Institute on Drug Abuse
  • National Institute on Drug Abuse
  • National Institute on Drug Abuse
  • National Institute on Drug Abuse


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