Airway nociceptors activated by pro-inflammatory cytokines

Yu, Jerry; Lin, Shuxin; Zhang, Jingwen; Otmishi, Peyman; Guardiola, Juan

doi:10.1016/j.resp.2006.11.005

Cited by 65 publications

(42 citation statements)

References 10 publications

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“…For example, pronounced increases in the plasma levels of tumor necrosis factor-␣ (TNF-␣), interleukin (IL)-1, IL-6, and IL-10 have been reported in the studies when hemorrhage of similar intensity and duration of hypotension as that in our study was induced (1). Some of these cytokines such as TNF-␣ and IL-1␤ are known to exert potent stimulatory and/or sensitizing effects on vagal pulmonary C-fiber afferents (16,22,31).…”

Section: Discussionsupporting

confidence: 65%

Hemorrhagic hypotension-induced hypersensitivity of vagal pulmonary C-fibers to chemical stimulation and lung inflation in anesthetized rats

Lin

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Lin RL, Lin YJ, Xu F, Lee LY. Hemorrhagic hypotensioninduced hypersensitivity of vagal pulmonary C-fibers to chemical stimulation and lung inflation in anesthetized rats. Am J Physiol Regul Integr Comp Physiol 308: R605-R613, 2015. First published January 14, 2015 doi:10.1152/ajpregu.00424.2014.-This study was carried out to investigate whether hemorrhagic hypotension (HH) altered the sensitivity of vagal pulmonary C-fibers. The fiber activity (FA) of single vagal pulmonary C-fiber was continuously recorded in anesthetized rats before, during, and after HH was induced by bleeding from the femoral arterial catheter into a blood reservoir and lowering the mean systemic arterial pressure (MSAP) to ϳ40 mmHg for 20 min. Our results showed the following. First, after MSAP reached a steady state of HH, the peak FA response to intravenous injection of capsaicin was elevated by approximately fivefold. The enhanced C-fiber sensitivity continued to increase during HH and sustained even after MSAP returned to baseline during the recovery, but slowly returned to control ϳ20 min later. Second, responses of FA to intravenous injections of other chemical stimulants of pulmonary C-fibers (phenylbiguanide, lactic acid, and adenosine) and a constantpressure lung hyperinflation were all significantly potentiated by HH. Third, infusion of sodium bicarbonate alleviated the systemic acidosis during HH, and it also attenuated, but did not completely prevent, the HH-induced C-fiber hypersensitivity. In conclusion, the pulmonary C-fiber sensitivity was elevated during HH, probably caused by the endogenous release of chemical substances (e.g., lactic acid) that were produced by tissue ischemia during HH. This enhanced C-fiber sensitivity may heighten the pulmonary protective reflexes mediated through these afferents (e.g., cough, J reflex) during hemorrhage when the body is more susceptible to other hazardous insults and pathophysiological stresses.hemorrhage; pulmonary; C-fiber; hypoxia; hypersensitivity VAGAL BRONCHOPULMONARY C-fibers represent ϳ75% of the vagal afferents arising from the lung and airways (17). These unmyelinated afferents innervate the entire respiratory tract and play an important role in regulating the respiratory functions under various physiological and pathophysiological conditions (5, 21). Activation of these afferents elicits centrally mediated protective reflex responses via the cholinergic pathway, which include laryngeal closure, bronchoconstriction and airway hypersecretion, accompanied by cough, airway irritation, dyspneic sensation, and J reflex (5, 21). Activation of these sensory nerves can also trigger release of tachykinins and calcitonin gene-related peptide from the sensory terminals, which can act on a number of effector cells in the respiratory tract (e.g., smooth muscles, cholinergic ganglia, mucous glands, immune cells), and elicit the local "axon reflexes" such as bronchoconstriction, protein extravasation, and inflammatory cell chemotaxis (5, 18, 21).Tissue ischemia is known to activate C-fib...

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Section: Discussionsupporting

confidence: 65%

Hemorrhagic hypotension-induced hypersensitivity of vagal pulmonary C-fibers to chemical stimulation and lung inflation in anesthetized rats

Lin

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Although airway sensory nerves, such as C fibers (21) and HTA-delta fibers (42), play a central role in airway regulation, recent studies (12) show that NPY, a cotransmitter and neuromodulator in sympathetic nerves, also plays an important role in the regulation of physiological and pathophysiological processes in the respiratory system. However, previous studies examining age-related changes in airway innervation and neurotransmitter expression in young animals and children are very limited.…”

Section: Discussionmentioning

confidence: 99%

Early postnatal exposure of mice to side-steam tobacco smoke increases neuropeptide Y in lung

Benders

Hunter

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Wu ZX, Benders KB, Hunter DD, Dey RD. Early postnatal exposure of mice to side-steam tobacco smoke increases neuropeptide Y in lung. Am J Physiol Lung Cell Mol Physiol 302: L152-L159, 2012. First published October, 14, 2011 doi:10.1152/ajplung.00071.2011.-Our recent study showed that prenatal and early postnatal exposure of mice to sidesteam tobacco smoke (SS), a surrogate to environmental tobacco smoke (ETS), leads to increased airway responsiveness and sensory innervation later in life. However, the underlying mechanism initiated in early life that affects airway responses later in life remains undefined. The concomitant increase in nerve growth factor (NGF) after exposures suggests that NGF may be involved the regulation of airway innervation. Since NGF regulates sympathetic nerve responses, as well as sensory nerves, we extended previous studies by examining neuropeptide Y (NPY), a neuropeptide associated with sympathetic nerves. Different age groups of mice, postnatal day (PD) 2 and PD21, were exposed to either SS or filtered air (FA) for 10 consecutive days. The level of NPY protein in lung and the density of NPY nerve fibers in tracheal smooth muscle were significantly increased in the PD2-11SS exposure group compared with PD2-11FA exposure. At the same time, the level of NGF in lung tissue was significantly elevated in the PD2-11SS exposure groups. However, neither NPY (protein or nerves) nor NGF levels were significantly altered in PD21-30SS exposure group compared with the PD21-30FA exposure group. Furthermore, pretreatment with NGF antibody or K252a, which inhibits a key enzyme (tyrosine kinase) in the transduction pathway for NGF receptor binding, significantly diminished SS-enhanced NPY tracheal smooth muscle innervation and the increase in methacholine-induced airway resistance. These findings show that SS exposure in early life increases NPY tracheal innervation and alters pulmonary function and that these changes are mediated through the NGF. airway innervation; asthma; secondhand smoke; neurotrophic factor ENVIRONMENTAL TOBACCO SMOKE (ETS) is an environmental trigger factor that leads to airway inflammation and asthma symptoms in susceptible individuals and animals (25,33,34). Exposure to ETS in utero or during early postnatal development increases the incidence of respiratory illnesses (11,13,28,31,35) later in life. Epidemiological studies (11,13,25,28,(32)(33)(34)(35) show that the probability of developing or exacerbating childhood asthma increases in children of mothers who smoke cigarettes. These results suggest that the prenatal and early postnatal periods are critical periods of developmental sensitivity to cigarette smoke exposure. Indeed, our recent study (40) showed that exposure to side-steam tobacco smoke (SS) during prenatal and early postnatal life produces changes in lung function and airway innervation later in life, supporting the concept of an early life critical period of susceptibility. However, the underlying mechanism initiated by early life exposures that affect lung st...

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“…Recent reports have shown that nociceptors in the airways express receptors for IL-1␤ and TNF-␣ and are stimulated by cytokines. C-fibers respond to stimulation with IL-1␤ and TNF-␣ by increasing their electrical activities and vagal afferent activity (18,35,37). Submucosal glands are stimulated by C-fibers throughout axon reflex and anterograde release of the neurotransmitter substance P and, possibly, VIP and Ach (5,12,17).…”

Section: Discussionmentioning

confidence: 99%

The cytokines interleukin-1β and tumor necrosis factor-α stimulate CFTR-mediated fluid secretion by swine airway submucosal glands

Baniak

Luan

Grunow

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Airway nociceptors activated by pro-inflammatory cytokines

Cited by 65 publications

References 10 publications

Hemorrhagic hypotension-induced hypersensitivity of vagal pulmonary C-fibers to chemical stimulation and lung inflation in anesthetized rats

Hemorrhagic hypotension-induced hypersensitivity of vagal pulmonary C-fibers to chemical stimulation and lung inflation in anesthetized rats

Early postnatal exposure of mice to side-steam tobacco smoke increases neuropeptide Y in lung

The cytokines interleukin-1β and tumor necrosis factor-α stimulate CFTR-mediated fluid secretion by swine airway submucosal glands

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