SENSORY DENERVATION BY NEONATAL CAPSAICIN TREATMENT EXACERBATES MYCOPLASMA-PULMONIS INFECTION IN RAT AIRWAYS

Mycoplasma pulmonis infection in rats results in life-long disease, ch aracterized by chronic inflammation of the airway mucosa with widespre ad accumulation of lymphoid tissue, mucous cell hyperplasia, and mucos al thickening. In addition, there is angiogenesis and increased sensit ivity of mucosal blood vessels to substance P (SP), so tachykinins rel eased from sensory nerve fibers cause an abnormally large amount of pl asma leakage. We sought to learn whether the sensory nerves influence the severity of the chronic inflammatory response of M. pulmonis infec tion. Our strategy was to destroy the nerves by capsaicin pretreatment at birth, infect the rats with M. pulmonis at 8 wk of age, and then s tudy the animals 6 wk later. We found that capsaicin pretreatment incr eased the severity of the infection, exaggerated the pathological chan ges in the tracheal mucosa, and increased the amount of SP-induced pla sma leakage, as quantified with Monastral blue. The thickness of the t racheal mucosa in these infected rats was 80% greater than in their ve hicle-pretreated counterparts and 200% greater than in the pathogen-fr ee controls. The area density of Monastral blue-labeled blood vessels averaged 20% in the infected rats pretreated with capsaicin, which rep resented a 40-fold increase over the leakage in the pathogen-free grou p. By comparison, the amount of Monastral blue labeling was only 13% i n rats pretreated with vehicle (P < 0.05), which was a 22-fold increas e over the corresponding pathogen-free group. The number of SP-immunor eactive nerves fibers was reduced both by neonatal capsaicin and by in fection (87 and 63% reductions, respectively); but when the two condit ions were combined, their effects were not additive (79% reduction), p erhaps because of nerve regrowth. We conclude that destruction of sens ory nerves increases the severity of infection-induced chronic inflamm ation in the airway mucosa, with exaggerated mucosal thickening, angio genesis, plasma leakage, and nerve remodeling.