Allergic inflammation-induced neuropeptide production in rapidly adapting afferent nerves in guinea pig airways.
In the vagal-sensory system, neuropeptides such as substance P and calcitonin gene-related peptide (CGRP) are synthesized nearly exclusively in small-diameter nociceptive type C-fiber neurons. By definition, these neurons are designed to respond to noxious or tissue-damaging stimuli. A common feature of visceral inflammation is the elevation in production of sensory neuropeptides. Little is known, however, about the physiological characteristics of vagal sensory neurons induced by inflammation to produce substance P. In the present study, we show that allergic inflammation of guinea pig airways leads to the induction of substance P and CGRP production in large-diameter vagal sensory neurons. Electrophysiological and anatomical evidence reveals that the peripheral terminals of these neurons are low-threshold Adelta mechanosensors that are insensitive to nociceptive stimuli such as capsaicin and bradykinin. Thus inflammation causes a qualitative change in chemical coding of vagal primary afferent neurons. The results support the hypothesis that during an inflammatory reaction, sensory neuropeptide release from primary afferent nerve endings in the periphery and central nervous system does not require noxious or nociceptive stimuli but may also occur simply as a result of stimulation of low-threshold mechanosensors. This may contribute to the heightened reflex physiology and pain that often accompany inflammatory diseases.
Myers
Allen C
AC
Department of Medicine, The Johns Hopkins Asthma and Allergy Center, JHU School of Medicine, 5501 Hopkins Bayview Circle A162, Baltimore, MD 21224, USA.
Kajekar
Radhika
R
Undem
Bradley J
BJ
D000222:Adaptation, Physiological / Q000276:immunology; D000542:Alveolitis, Extrinsic Allergic / Q000378:metabolism*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D006168:Guinea Pigs; D008168:Lung / Q000276:immunology* / Q000294:innervation* / Q000378:metabolism; D008297:Male; D008465:Mechanoreceptors / Q000276:immunology / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009412:Nerve Fibers / Q000276:immunology / Q000378:metabolism; D016900:Neurofilament Proteins / Q000032:analysis; D009475:Neurons, Afferent / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D009620:Nodose Ganglion / Q000166:cytology; D013373:Substance P / Q000378:metabolism*
D016900:Neurofilament Proteins; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin