Disclaimers: None.
You have free access to this content
The neurophysiology of dyspnea
Article first published online: 18 DEC 2008
DOI: 10.1111/j.1476-4431.2008.00372.x
© Veterinary Emergency and Critical Care Society 2008
Issue

Journal of Veterinary Emergency and Critical Care
Volume 18, Issue 6, pages 561–571, December 2008
Additional Information
How to Cite
Mellema, M. S. (2008), The neurophysiology of dyspnea. Journal of Veterinary Emergency and Critical Care, 18: 561–571. doi: 10.1111/j.1476-4431.2008.00372.x
Publication History
- Issue published online: 18 DEC 2008
- Article first published online: 18 DEC 2008
References
- 1ATS. Dyspnea. Mechanisms, assessment, and management: a consensus statement. American Thoracic Society. Am J Respir Crit Care Med 1999; 159 (1):321–340.
- 2, , Humane and practical implications of using carbon dioxide mixed with oxygen for anesthesia or euthanasia of rats. Lab Anim Sci 1997; 47 (4):376–385.
- 3
- 4, Assessment of animal pain in farm animals using behavioral and physiological measurements. J Anim Sci 1997; 75 (1):266–272.
- 5
- 6, , When it's hard breathe, maybe pain doesn't matter. J Neurophysiol 2007; 97:959–960.
- 7, , The course of symptom frequency and intensity in advanced cancer patients followed at home. J Pain Symptom Manage 2000; 20 (2):104–112.
- 8
- 9, , , et al. The relationship of nausea and dyspnea to pain in seriously ill patients. Pain 1997; 71 (2):149–156.
- 10, , , et al. Experimental pain augments experimental dyspnea, but not vice versa in human volunteers. Anesthesiology 1999; 91 (6):1633–1638.
- 11, , , et al. Dyspnea as a noxious sensation: inspiratory threshold loading may trigger diffuse noxious inhibitory controls in humans. J Neurophysiol 2007; 97:1396–1404.
- 12, , , et al. CO2 consensus report, In: Newcastle Consensus Meeting on Carbon Dioxide Euthanasia of Laboratory Animals. UK: University of Newcastle upon Tyne; 2006: 1–17.
- 13, , . Brain responses associated with consciousness of breathlessness (air hunger). Proc Natl Acad Sci USA 2001; 98 (4):2035–2040.
- 14, , Aversion to carbon dioxide. Lab Anim 2005; 39 (4):453–455.
- 15, , . Hypoxic and hypercapnic drives to breathe generate equivalent levels of air hunger in humans. J Appl Physiol 2003; 94 (1):141–154.
- 16Behaviour of pigs exposed to mixtures of gases and the time required to stun and kill them: welfare implications. Vet Rec 1999; 144 (7):165–168.
- 17, , . Chemosensitivity and perception of dyspnea in patients with a history of near-fatal asthma. N Engl J Med 1994; 330 (19):1329–1334.
- 18, , . The use of reliever medication in asthma: the role of negative mood and symptom reports. J Asthma 2003; 40 (4):357–365.
- 19, Patient mislabeling of symptoms and rehospitalization in asthma. J Asthma 1983; 20 (1):43–44.
- 20, , The risk of hospitalization and near-fatal and fatal asthma in relation to the perception of dyspnea. Chest 2002; 121 (2):329–333.
- 21, Perception of asthma. Lancet 1976; 1:882–884.
- 22, , , et al. Respiratory-related evoked potentials in children with life-threatening asthma. Am J Respir Crit Care Med 2000; 161 (6):1830–1835.
- 23, P3-specific amplitude reductions to respiratory and auditory stimuli in subjects with asthma. Am J Respir Crit Care Med 2002; 166 (1):47–52.
- 24, , . Perception of bronchial obstruction in asthmatic patients. Relationship with bronchial eosinophilic inflammation and epithelial damage and effect of corticosteroid treatment. J Clin Invest 1995; 96 (1):12–21.
- 25Airway receptors. Respir Physiol 2001; 125 (1–2):3–15.
- 26, , . Cold facial stimulation reduces breathlessness induced in normal subjects. Am Rev Respir Dis 1987; 136 (1):58–61.
- 27, , . Oral mucosal stimulation modulates intensity of breathlessness induced in normal subjects. Am Rev Respir Dis 1991; 144 (2):419–422.
- 28, , . Does cold air affect exercise capacity and dyspnea in stable chronic obstructive pulmonary disease? Chest 1993; 103 (3):693–696.
- 29, An overview of the anatomy and physiology of slowly adapting pulmonary stretch receptors. Respir Physiol 2001; 125 (1–2):17–31.
- 30Overview of neural pathways in allergy and asthma. Pulm Pharmacol Ther 2003; 16 (1):23–30.
- 31, , . Reduced tidal volume increases ‘air hunger’ at fixed PCO2 in ventilated quadriplegics. Respir Physiol 1992; 90 (1):19–30.
- 32, Reflex effects of pulmonary venous congestion: role of vagal afferents. News Physiol Sci 1990; 5:95–99.
- 33, , . Substance P contributes to rapidly adapting receptor responses to pulmonary venous congestion in rabbits. J Physiol 1996; 493 (Part 1):229–238.
- 34Afferent receptors in the airways and cough. Respir Physiol 1998; 114 (1):5–15.
- 35, Stimulation of lung irritant receptors by cigarette smoke, carbon dust, and histamine aerosol. J Appl Physiol 1971; 31 (1):15–19.
- 36, , Exposing guinea pigs to ozone for 1 wk enhances responsiveness of rapidly adapting receptors. J Appl Physiol 1998; 84 (4):1190–1197.
- 37Neurogenic inflammation in the airways. Respir Physiol 2001; 125 (1–2):145–154.
- 38, Afferent vagal C fibre innervation of the lungs and airways and its functional significance. Rev Physiol Biochem Pharmacol 1984; 99:1–110.
- 39, , . Effect of chest wall vibration on breathlessness in normal subjects. J Appl Physiol 1991; 71 (1):175–181.
- 40, , Effect of lung volume on breath holding. J Appl Physiol 1987; 62 (5):1962–1969.
- 41, , . Effects of chest wall vibration on breathlessness during hypercapnic ventilatory response. J Appl Physiol 1998; 84 (5):1487–1491.
- 42, , , et al. Oscillation of the lung by chest-wall vibration. Respir Physiol 2001; 126 (3):245–249.
- 43, , , et al. Gate mechanism in breathlessness caused by chest wall vibration in humans. J Appl Physiol 1984; 56 (1):8–11.
- 44, , . ‘Air hunger’ from increased PCO2 persists after complete neuromuscular block in humans. Respir Physiol 1990; 81 (1):1–17.
- 45, Respiratory-associated rhythmic firing of midbrain neurons is modulated by vagal input. Respir Physiol 1992; 90 (1):31–46.
- 46, , , et al. Dyspnea: a sensory experience. Lung 1990; 168 (4):185–199.
- 47, , Respiratory-associated rhythmic firing of midbrain neurones in cats: relation to level of respiratory drive. J Physiol 1991; 437:305–325.
- 48, , Respiratory-associated thalamic activity is related to level of respiratory drive. Respir Physiol 1992; 90 (1):99–113.
- 49, , . Acute partial paralysis alters perceptions of air hunger, work and effort at constant P(CO(2)) and V(E). Respir Physiol 2000; 122 (1):45–60.
- 50, , . Large lesions in the pre-Botzinger complex area eliminate eupneic respiratory rhythm in awake goats. J Appl Physiol 2004; 97 (5):1629–1636.
- 51, , . BOLD fMRI identifies limbic, paralimbic, and cerebellar activation during air hunger. J Neurophysiol 2002; 88 (3):1500–1511.
- 52, , . Breathlessness in humans activates insular cortex. Neuroreport 2000; 11 (10):2117–2120.
- 53, , . Neural substrates for the perception of acutely induced dyspnea. Am J Respir Crit Care Med 2001; 163 (4):951–957.
- 54, , , et al. Fear and the human amygdala. J Neurosci 1995; 15 (9):5879–5891.
- 55, , , et al. Organization of visceral and limbic connections in the insular cortex of the rat. J Comp Neurol 1991; 311 (1):1–16.
- 56, The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb Cortex 2000; 10 (3):206–219.
- 57The application of positron emission tomography to the study of normal and pathologic emotions. J Clin Psychiatry 1997; 58 (suppl 16):4–12.
- 58, , . The perception of respiratory work and effort can be independent of the perception of air hunger. Am J Respir Crit Care Med 2000; 162 (5):1690–1696.
- 59, , , et al. The Fowler breathholding study revisited: continuous rating of respiratory sensation. Respir Physiol 1994; 95 (1):53–66.
- 60, , , et al. Effects of voluntary constraining of thoracic displacement during hypercapnia. J Appl Physiol 1987; 63 (5):1822–1828.
- 61, , . Breathlessness induced by dissociation between ventilation and chemical drive. Am Rev Respir Dis 1989; 139 (5):1231–1237.
- 62, Pathophysiology of dyspnea. N Engl J Med 1995; 333 (23):1547–1553.
- 63, , . Distinguishable sensations of breathlessness induced in normal volunteers. Am Rev Respir Dis 1989; 140:1021–1027.
- 64, , The effect of respiratory muscle fatigue on respiratory sensations. Clin Sci (Lond) 1981; 60 (4):463–466.
- 65, , , et al. Effect of increased lung volume on perception of breathlessness, effort, and tension. J Appl Physiol 1984; 57 (3):686–691.
- 66, , , et al. “Tightness” sensation of asthma does not arise from the work of breathing. Am J Respir Crit Care Med 2002; 165 (1):78–82.
- 67, Respiratory sensations in asthma: physiological and clinical implications. J Asthma 2001; 38 (6):447–460.
- 68, Respiratory mechanics in airways obstruction associated with inspiratory dyspnoea. Thorax 1976; 31 (6):669–677.
- 69, , , et al. Distinguishable types of dyspnea in patients with shortness of breath. Am Rev Respir Dis 1990; 142 (5):1009–1014.
- 70, , . Quality of dyspnea in bronchoconstriction differs from external resistive loads. Am J Respir Crit Care Med 2000; 162 (2, Part 1):451–455.
- 71, , , et al. Respiratory sensation and ventilatory mechanics during induced bronchoconstriction in spontaneously breathing low cervical quadriplegia. Am J Respir Crit Care Med 2002; 166 (3):370–376.
- 72, , . Protective effect of inhaled furosemide on allergen-induced early and late asthmatic reactions. N Engl J Med 1989; 321 (16):1069–1073.
- 73, , Effect of frusemide on cough responses to chloride-deficient solution in normal and mild asthmatic subjects. Eur Respir J 1993; 6 (6):862–867.
- 74
- 75, Nebulized furosemide as a novel treatment for dyspnea in terminal cancer patients. J Pain Symptom Manage 2002; 23 (1):73–76.
- 76, , , et al. Inhaled furosemide greatly alleviates the sensation of experimentally induced dyspnea. Am J Respir Crit Care Med 2000; 161 (6):1963–1967.
- 77, , Responses of tracheobronchial receptors to inhaled furosemide in anesthetized rats. Am J Respir Crit Care Med 2000; 162 (3, Part 1):971–975.
- 78
- 79, , . Excitatory mechanism of veratridine on slowly adapting pulmonary stretch receptors in anesthetized rabbits. Life Sci 1998; 63 (16):1431–1437.
- 80, , Effects of inhaled furosemide on CO(2) ventilatory responsiveness in humans. Pulm Pharmacol Ther 2002; 15 (4):363–368.
- 81, , . Effect of inhaled furosemide on air hunger induced in healthy humans. Respir Physiol Neurobiol 2007; 156:1–8.
- 82, , Inhaled furosemide inhibits behavioral response to airway occlusion in anesthetized cats. Anesthesiology 2001; 95 (5):1234–1237.
- 83, , Lung opioid receptors: pharmacology and possible target for nebulized morphine in dyspnea. Life Sci 2000; 66 (23):2221–2231.
- 84, , . Effects of dihydrocodeine, alcohol, and caffeine on breathlessness and exercise tolerance in patients with chronic obstructive lung disease and normal blood gases. N Engl J Med 1981; 305 (27):1611–1616.
- 85, Dyspnea: pathophysiology and management. J Pain Symptom Manage 1997; 13:220–232.
- 86
- 87, Management of dyspnea and cough in patients with cancer. Hematol Oncol Clin North Am 1996; 10 (1):157–171.
- 88, Clinical application of nebulized opioids for treatment of dyspnoea in patients with malignant disease. Support Care Cancer 1994; 2 (3):184–187.
- 89, , Nebulised morphine. Lancet 1993; 342 (8879):1123–1124.
- 90, , , et al. Endorphins and the control of breathing. Ability of nalaxone to restore flow-resistive load compensation in chronic obstructive pulmonary disease. N Engl J Med 1981; 304 (20):1190–1195.
- 91, , . Effect of nalaxone on maximal exercise performance and control of ventilation in COPD. Chest 1989; 96 (4):761–766.
- 92, , Modulation of cholinergic neurotransmission in guinea pig airways by opioids. Br J Pharmacol 1990; 100 (1):131–137.
- 93, , Both the cholinergic and non-cholinergic components of airway excitation are inhibited by morphine in the guinea pig. Acta Physiol Scand 1989; 135 (3):411–415.
- 94, Modulation of cholinergic neurotransmission in airways by enkephalin. J Appl Physiol 1985; 58 (3):853–858.
- 95, Peripheral versus central cardiorespiratory effects of morphine. Neuropharmacology 1982; 21 (10):1019–1026.
- 96, , . Influence of beclomethasone and salmeterol on the perception of methacholine-induced bronchoconstriction. Chest 1998; 114 (2):373–379.
- 97, , . The perception of dyspnoea in patients with asthma, before and following treatment with inhaled glucocorticosteroids. Respir Med 2000; 94 (2):161–165.
- 98, , . Inhaled corticosteroids, combined with long-acting beta(2)-agonists, improve the perception of bronchoconstriction in asthma. Am J Respir Crit Care Med 2001; 164 (5):764–769.
- 99, , , et al. Perception of airway narrowing during reduction of inhaled corticosteroids and asthma exacerbation. Thorax 2003; 58 (12):1042–1047.
- 100, , . Effect of budesonide on the perception of induced airway narrowing in subjects with asthma. Am J Respir Crit Care Med 2002; 165 (1):15–21.
- 101, Influence of treatment with beclomethasone, cromoglycate and theophylline on perception of bronchoconstriction in patients with bronchial asthma. Clin Sci (Lond) 1996; 90 (3):227–234.
- 102, , . Impaired perception of dyspnea in patients with severe asthma. Relation to sputum eosinophils. Am J Respir Crit Care Med 1998; 158 (4):1134–1141.
- 103, , . Do inhaled corticosteroids affect perception of dyspnea during bronchoconstriction in asthma? Chest 2001; 120 (3):770–777.
- 104, , , et al. Does an IV bolus of methylprednisolone relieve dyspnea in asthma exacerbations? Chest 2000; 118 (6):1530–1537.
- 105, , . Do steroids interfere in dyspnoea sensation? Respir Med 2002; 96 (7):511–514.
- 106, , . In-phase chest wall vibration decreases dyspnea during arm elevation in chronic obstructive pulmonary disease patients. Intern Med 1998; 37 (10):831–835.
- 107, , , et al. Mechanical chest-wall vibration does not relieve air hunger. Respir Physiol Neurobiol 2003; 134 (3):177–190.
- 108, , . Second-hand exposure to aerosolized intravenous anesthetics propofol and fentanyl may cause sensitization and subsequent opiate addiction among anesthesiologists and surgeons. Med Hypotheses 2006; 66 (5):874–882.

1476-4431/asset/olbannerleft.gif?v=1&s=1198e742bbbdf6a74b8cd41ab80445cebba03d3c)
1476-4431/asset/olbannerright.gif?v=1&s=2f073f06b827aa98d20490e80641e603df213ad0)