Sensory denervation by neonatal capsaicin treatment exacerbates
mycoplasma pulmonis infection in rat airways.
Bowden, Jeffrey J., Peter Baluk, Peter M. Lefevre, Trenton R. Schoeb,
J. Russell Lindsey, and Donald M. McDonald.
Cardiovascular Research Institute and Department of Anatomy,
University of California, San Francisco, CA 94143, Department of
Comparative Medicine, University of Florida, Gainsville, FL 32610 and
The Birmingham Veterans Administration Medical Center and Department
of Comparative Medicine, University of Alabama at Birmingham,
Birmingham, AL 35294
APStracts 2:0190L, 1995.
Mycoplasma pulmonis infection in rats results in life-long disease,
characterized by chronic inflammation of the airway mucosa, with
widespread accumulation of lymphoid tissue, mucous cell hyperplasia,
and mucosal thickening. In addition, there is angiogenesis and
increased sensitivity of mucosal blood vessels to substance P, so
tachykinins released from sensory nerve fibers cause an abnormally
large amount of plasma leakage. We sought to learn whether the
sensory nerves influence the severity of the chronic inflammatory
response of M. pulmonis infection. Our strategy was to destroy the
nerves by capsaicin pretreatment at birth, infect the rats with M.
pulmonis at 8 weeks of age, and then study the animals 6 weeks later.
We found that capsaicin pretreatment increased the severity of the
infection, exaggerated the pathological changes in the tracheal
mucosa, and increased the amount of substance P-induced plasma
leakage, as quantified with Monastral blue. The thickness of the
tracheal mucosa in these infected rats was 80% greater than in their
vehicle pretreated counterparts and 200% greater than in the
pathogen-free controls. The area density of Monastral blue-labeled
blood vessels averaged 20% in the infected rats pretreated with
capsaicin, which represented a 40-fold increase over the leakage in
the pathogen-free group. By comparison, the amount of Monastral blue
labeling was only 13% in rats pretreated with vehicle (P <
0.05), which was a 22-fold increase over the corresponding pathogen
-free group. The number of substance P-immunoreactive nerves fibers
was reduced both by neonatal capsaicin and by infection (87% and 63%
reductions respectively), but when the two conditions were combined,
their effects were not additive (79% reduction), perhaps because of
nerve regrowth. We conclude that destruction of sensory nerves
increases the severity of infection-induced chronic inflammation in
the airway mucosa, with exaggerated mucosal thickening, angiogenesis,
plasma leakage, and nerve remodeling.
Received 20 October 1994; accepted in final form 27 September
1995.
APS Manuscript Number L301-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95