# NEUROGENIC CONTRIBUTION TO JOINT INJURY IN ARTHRITIS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1988 · $158,362

## Abstract

Focal neurological lesions are known to dramatically attenuate the later
development of rheumatoid arthritis (RA) in humans and experimental
arthritis (EA) in animals.  in preliminary experiments we have found that
joints at higher risk of developing EA are more densely innervated by
small-diameter substance P-containing nociceptive afferent neurons.  In
addition, we found that prior treatment of the nerves in one extremity with
capsaicin, which selectively depletes substance P and other transmitters in
small-diameter primary afferents, results in unilateral arthritis.  A
pathogenetic role for substance P (SP) in the development of arthritis is
suggested by the fact that SP can be released into the peripheral tissues,
where it exerts a pro-inflammatory effect.  We propose to confirm these
observations and to test the hypothesis that the modulation of the
development of arthritis in the rat is mediated by neural influences on the
blood flow and vascular permeability of the synovial membrane.  There is no
pathognomonic laboratory test for RA.  Its diagnosis is based on the
presence of a constellation of signs and symptoms.  The bilateral symmetry
of RA, an important diagnostic clinical feature which also appears in all
forms of experimental arthritis in animals, is not explained by any
hypothesized pathogenetic mechanism.  We propose to test the hypothesis
that production of bilaterally symmetric disease requires activity of
somato-sympathetic nociceptive reflexes.  In preliminary experiments we
have found that contralateral swelling, induced by the injection of a
noxious stimulus into the paw; can be blocked by pretreating nerves in the
injected paw with capsaicin.  We propose to extend our studies of the
neural mechanisms of this contralateral swelling reflect (CSR) and to test
the hypothesis that establishment of bilateral symmetry in EA requires
activity in such a somatosympathetic nociceptive reflex.  There are many
important gaps in our knowledge of the neurobiology of the joint.  The
proposed experiments will employ recent advances in peptide neurobiology to
study the role of the peripheral nervous system in the pathogenesis of
experimentally-induced arthritis in the rat.

## Key facts

- **NIH application ID:** 3156366
- **Project number:** 5R01AR032634-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** JON DAVID LEVINE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $158,362
- **Award type:** 5
- **Project period:** 1983-08-01 → 1992-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156366

## Citation

> US National Institutes of Health, RePORTER application 3156366, NEUROGENIC CONTRIBUTION TO JOINT INJURY IN ARTHRITIS (5R01AR032634-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156366. Licensed CC0.

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