ROLE OF PERIPHERAL CRF DURING INFLAMMATION AND PAIN

Project: Research project

Project Details

Description

Previous studies have demonstrated that a peripheral corticotropin
releasing factor (PCRF), which possesses CRF-like immunological and
biological activity, is released from injured tissue during inflammation.
Additional studies have demonstrated that synthetic CRF possesses potent
antinociceptive and anti-inflammatory activity when injected directly into
inflamed tissue. However, there is a gap in knowledge regarding the
identity and regulation of release of peripheral CRF and regarding the
mechanism(s) of action for the antinociceptive and anti-inflammatory
effects of synthetic CRF. The objectives of this proposal will 1) identify
the peripheral origin of CRF released during inflammation; 2) characterize
the regulation of peripheral CRF release; 3) determine the effects of CRF
on modulating the peripheral release of markers of primary afferents
(immunoreactive substance P, CGRP), sympathetic fibers (immunoreactive NPY)
and leukocytes (immunoreactive LTB4 and beta-endorphin); and 4) determine
whether CRF-induced modulation of primary afferents, sympathetics or
leukocytes contributes to its mechanism of action. Samples of PCRF and
inflammatory mediators will be collected by subcutaneous placement of
microdialysis probes into carrageenan-inflamed hindpaws of rats. The PCRF
will be compared to synthetic CRF for its physicochemical similarity (HPLC
elution profile, protease and oxidation susceptibility) and quantitated for
CRF-like immunoreactivity (using a CRF radioimmunoassay) and CRF-like
biological activity (using release of immunoreactive beta-endorphin from
pituitary cultures). Levels of immunoreactive substance P, CGRP, NPY, LTB4
and beta-endorphin will be measured by previously validated
radioimmunoassays. Collectively, this research proposal will evaluate the
hypothesis of a new peripheral neuroendocrine axis, in which the process of
inflammation leads to the local release and actions of an
antinociceptive/anti-inflammatory peptide, CRF.
StatusFinished
Effective start/end date4/1/923/31/97

Funding

  • National Institutes of Health: $87,528.00
  • National Institutes of Health
  • National Institutes of Health: $99,404.00
  • National Institutes of Health
  • National Institutes of Health: $85,248.00

ASJC

  • Medicine(all)
  • Dentistry(all)

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