Neurogenic Inflammation: Literature on Toluene Diisocyanate

William Meggs's recent article, "Neuro-genic Inflammation and Sensitivity to Environmental chemicals" (EHP 101:234-238), provides a useful introduction to a rapidly growing area of knowledge in physiology and posits a number of interesting hypotheses regarding the health effects of airborne chemicals. Some specific technical points, however, merit comment. Meggs describes the common chemical sense as "a nasal sensation provoked by airborne chemicals" (p. 234, my emphasis). This statement is correct as far as it goes, but it neglects to mention that the trigemi-nal nerve also innervates the oral cavity and that ingested irritants (e.g., capsaicin, the irritant in hot peppers, and allyl isothio-cyanate, the irritant in horseradish) trigger some of the same reflexes as inhaled irri-tants. Thus, so-called gustatory rhinitis involves rhinorrhea, nasal congestion, and facial sweating after ingestion of "hot" (spicy) foods (1). As to whether the common chemical sense was only "recently separated" from olfaction as a sensory modality (p. 235), the 1990 study of odor and nasal pungency in anosmics cited by Meggs (2) is but the latest in a series stretching back over 80 years and utilizing various tools to separate the two sensory systems (3). Neuropeptide release occurs in relation to other types of airway reflexes, some of which do, indeed, involve an efferent limb coming from the central nervous system, as portrayed in Meggs's Figure 2. Gustatory rhinitis, for example, involves afferent trigeminal sensory fibers and efferent facial nerve cholinergic fibers and is blocked by the preadministration of atropine (1). In contrast to Figure 2, however, the axon reflex (whereby neuropeptides are released) is a primarily afferent process, involving release of neuropeptides from varicosities in sensory nerves (4). Thus, neuropeptide release can be thought of as a local, as opposed to a central, reflex. What is clear is that a complex interrelationship exists between local (neuropeptide-mediated) and central (adrenergic, cholinergic, and nonadrenergic/noncholinergic) airway reflexes. Each of these mechanisms, as well as mast-cell degranulation (atopy), is subject to various regulatory factors, ultimately influencing upper and lower airway reactivity to environmental stimuli. Meggs briefly mentions the variety of neuropeptides documented in human airways (substance P, calcitonin gene-related protein, neurokinin A, and others), but then goes on to focus on the role of substance P. The relative distribution of neu-ropeptides and their physiological actions appear to vary across species, making generalizations difficult at this time (5). For example, whereas substance P promotes neutrophil and eosinophil chemotaxis and adhesion, …