Sensitivity of vagal afferent endings to chemical irritants in the rat lung
Introduction
Morphological studies showed that the majority (∼75%) of vagal afferents innervating the lungs are nonmyelinated (C-) fibers (Agostoni et al., 1957). Increasing evidence suggests that these pulmonary C-fiber afferents play an important role in regulating airway functions and in defending the lungs against inhaled irritants (Coleridge and Coleridge, 1984, Coleridge and Coleridge, 1994, Lee and Pisarri, 2001). Because of the high sensitivity of these afferents to capsaicin, a pungent ingredient of hot pepper, ‘capsaicin-sensitive lung afferents’ are often considered synonymous with ‘pulmonary C-fiber afferents’. However, the functional evidence to support this contention has not been established. In fact, a stimulatory effect of capsaicin has been demonstrated recently on some of the thin myelinated (Aδ) afferents innervating the guinea pig trachea (Riccio et al., 1996). Similar effects of capsaicin on Aδ-fiber nociceptors in various somatic and visceral organ systems have been reported in other species (Holzer, 1991). Furthermore, it has been well documented that rapidly adapting pulmonary receptors (RARs) whose activities are conducted by thin myelinated fibers can also be activated by other chemical irritants (Sampson and Vidruk, 1975, Widdicombe, 1981, Kou and Lee, 1990).
The primary purpose of this study was to investigate the relationship between the conduction velocity of the vagal afferents arising from the lungs and their sensitivities to capsaicin, other chemical irritants, and lung inflation. In addition, we sought to answer the following specific questions: (1) What are the primary features of afferent properties of pulmonary C fibers, besides the conduction velocity, that may serve as reliable criteria for distinguishing them from myelinated pulmonary afferents? (2) Can thin myelinated afferents arising from the lungs, such as RARs, be stimulated by right-atrial injection of capsaicin? If so, are the capsaicin-sensitive myelinated afferents also sensitive to other chemical irritants? We conducted these experiments on rats because this species has been used extensively and increasingly as an animal model for the studies of neural control of breathing.
Section snippets
Animal preparation
The procedures described below were performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health and were approved by the University of Kentucky Institutional Animal Care and Use Committee.
Male Sprague-Dawley rats (weight: 320–495 g) were anesthetized initially with an intraperitoneal injection of α-chloralose (100 mg/kg; Sigma) and urethane (500 mg/kg; Sigma) dissolved in a 2% borax solution;
Results
A total of 205 vagal bronchopulmonary afferents (109 pulmonary C fibers, 55 RARs and 41 SARs) were studied in 122 anesthetized, open-chest rats; only the receptors whose conduction velocities were determined were included in our study. The average conduction velocities were 1.06±0.03, 17.1±1.0, and 18.2±1.1 m/sec for C fibers, RARs, and SARs, respectively; no significant difference was found between those of RARs and SARs. These receptors were distributed in all four lobes of the right lung,
Discussion
Capsaicin has been used extensively as a tool for identifying nonmyelinated afferents arising from various visceral and somatic organ systems because of its well-documented potent and selective stimulatory effect on these nociceptive endings (Holzer, 1991). However, an excitatory action of capsaicin on some thin myelinated (Aδ) afferents in other organ systems has also been reported in different species; for example, capsaicin has been shown to stimulate Aδ-fiber polymodal nociceptors (or group
Acknowledgements
The authors would like to thank Robert Morton for technical assistance. This study was supported in part by NIH grant HL58686 (USA) to L.Y. Lee, and NSC grant 89-2314-B-075-060 (Republic Of China) to C.Y. Ho.
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