Bronchoconstriction capsaicin-induced

Recently, a third generation of B2-receptor antagonists was developed examples are FR 173657, FR 172357, and NPC 18884. These antagonists block both human and animal B2 receptors and are orally active. They have been reported to inhibit bradykinin-induced bronchoconstriction in guinea pigs, carrageenin-induced inflammatory responses in rats, and capsaicin-induced nociception in mice. These antagonists have promise for the treatment of inflammatory pain in humans. 

Capsaicin causes transient bronchoconstriction and induces coughing, especially in individual with severe asthma, potentially triggering fatal crises [37]. These adverse respiratory effects are probably due to the limited capacity of respiratory tissues to metabolize capsaicin (see Section 4.3) [38], and are a major problem with the use of pepper sprays as antiriot agents [37]. Smokers are less sensitive to the respiratory effects of capsaicin, but asthmatic patients should avoid chilies and hot cuisine, as should people using drugs such as ACE-inhibitors, which have an intrinsic capacity to induce cough. 

In children, capsaicin spray was demonstrated to cause a severe bronchospasm and pulmonary edema (Winograd, 1977 Bdlmire et al, 1996). In the Billmire study, a 4-week-old infant was exposed to 5% pepper spray after discharge from a self-defense device. The infant suffered respiratory failure and hypoxemia, requiring immediate extracorporeal membrane oxygenation. Inhaled capsaicin causes an immediate increase in airway resistance (Fuller, 1991). This dose-dependent bronchoconstriction after capsaicin inhalation in humans is the same as that demonstrated in asthmatics and smokers (Fuller et al, 1985). The capsaicin-induced bronchoconstriction and release of substance P is due to stimulation of nonmyelinated afferent C-fibers. 

Buchan, P. and Adcock, J.J., Capsaicin-induced bronchoconstriction in the guinea pig Contribution of vagal cholinergic reflexes, local axon reflexes and their modulation by BW 443C81, Br. J. Pharmacol, 1 105, 448, 1992. 

Cook AJ, Woolf CJ, Wall PD, McMahon SB (1987) Dynamic receptive field plasticity in rat spinal cord dorsal horn following C-primary afferent input. Nature 325 151-153 Corboz MR, RiveUi MA, Egan RW, Tulshian D, Matasi J, Fawzi AB, Benbow L, Smith-Torhan A, Zhang H, Hey JA (2000) Nociceptin inhibits capsaicin-induced bronchoconstriction in isolated guinea pig lung. Eur J Pharmacol 402 171-179... 

Midgren B, Hansson L, Karlsson J-A, Simonsson BG, Persson CG (1992) Capsaicin-induced cough in humans. Am Rev Respir Dis 146 347-351 Mochizuki H, Shimizu T, Maeda S, Tokuyama K, Morikawa A, Kuruome T (1995) Relationship between ultrasonically nebulized distilled water-induced bronchoconstriction and acetic acid-induced cough in asthmatic children. J Allergy Chn Immunol 96 193-199 Morice AH, Higgins KS, Yeo WW (1992) Adaptation of the cough reflex with different types of stimulation. Eur Respir J 5 841-847... 

The biological actions of capsaicin are primarily attributable to release of the neuropeptide substance P, calcitonin gene-related peptide (CGRP), and neurokinin A from sensory neurons. These transmitters from primary sensory neurons communicate witir other cell types. They produce alterations in the airway mucosa and neurogenic inflammation of the respiratory epithelium, airway blood vessels, glands, and smooth muscle. Alterations in multiple effector organs lead to bronchoconstriction, increased vascular permeability, edema of the tracheobronchial mucosa, elevated mucosal secretion, and neutrophil chemotaxis (Tominack and Spyker, 1987). Capsaicin-induced effects of bronchoconstriction, vasodilation, and plasma protein extravasation are mediated by substance P. In addition, substance P can cause bronchoconstriction through stimulation of c-fibers in pulmonary and bronchial circulation. 

An occasional common side effect of capsaicin exposure is bronchoconstriction, in asthmatic people, caused by inhaled airborne particles. In nonasthmatic people, this induces a cough. This is prevented by washing the skin surface where capsaicin was applied after 30-40 minutes of exposure. Chronic overdosage can cause chronic gastritis, kidney and liver toxicity, and neurotoxic effects. 

Capsaicin, like the other irritant RCAs, also causes bronchoconstriction, but the mechanism is uncertain. Capsaicin releases substance P that can cause bronchoconstriction directly by activation of specific receptors or by release of histamine or other mediators. It may also cause reflex bronchoconstriction by stimulating C fibers in both pulmonary and bronchial circulation. Therefore, bronchoconstriction may be secondary to substance P release, or to a vagal reflex. The altered neurophysiology of sensory neurons in the airway mucosa induces the release of tachykinins and neurokinin A, which causes neuro-mediated inflammation of the epithelium, airway, blood vessels, glands, and smooth muscles. This leads to bronchoconstriction, mucus secretion, enhanced vascular permeability, and neutrophil chemotaxis. 

Fujimura M, Sakamoto S, Kamio Y, Matsuda T (1992) Effects of methacholine induced bronchoconstriction and procaterol induced bronchodilation on cough receptor sensitivity to inhaled capsaicin and tartaric acid. Thorax 47 441 45... 

Fontana GA, Lavorini E, Pistolesi M (2005) water aerosols and cough. In Redington AE, Morice AH (eds) Acute and chronic cough. Taylor Francis, Boca Raton, USA, pp 195-214 Freestone C, Eccles R (1997) Assessment of the antitussive efficacy of codeine in cough associated with the common cold. J Pharm Pharmacol 49 1045-1049 Fujimura M, Sakamoto S, Kamio Y, Matsuda T (1992) Effects of methachoUne-induced bronchoconstriction and procaterol-induced bronchodilation on cough receptor sensitivity to inhaled capsaicin and tartaric acid. Thorax 47 441 145... 

Russell, J. A, and Lai-Fook, S. J., 1979, Reflex bronchoconstriction induced by capsaicin in the dog,/. Appl. Physiol. Respir. Environ. Exercise Physiol. 47 961-967. 

A randomized, placebo controlled trial examined the effects of menthol (10 mg nebulized twice daily for 4 week on airway hyperresponsiveness in 23 patients with mild to moderate asthma. The diurnal variation in the peak expiratory ow rate (a value re ecting airway hyperexcitability) was decreased but the forced expiratory volume was not signi cantly altered. This indicated an improvement of airway hyperresponsiveness without affecting air ow limitation (Tamaoki et al., 1995). Later in vivo research examined the effect of menthol on airway resistance caused by capsaicin- and neurokinin induced bronchoconstriction there was a signi cant decrease in both cases by inhalation of menthol at 7.5 pg/L air concentration. The in vitro effect of menthol on bronchial rings was also studied. It was concluded that menthol attenuated bronchoconstriction by a direct action on bronchial smooth muscle (Wright et al., 1997). 

Wright CE, Laude EA, Grattan TJ, Morice AH (1997) Capsaicin and neurokinin A-induced bronchoconstriction in the anaesthetised guinea-pig evidence for a direct action of menthol on isolated bronchial smooth muscle. J Pharmacol 121 164516... 

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