Skip to main content

Advertisement

Log in

Neurology of allergic inflammation and rhinitis

  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Afferent nerves, derived from the trigeminal ganglion, and postganglionic autonomic nerves, derived from sympathetic and parasympathetic ganglia expressing many different neurotransmitters, innervate the nose. Reflexes that serve to optimize the air-conditioning function of the nose by altering sinus blood flow, or serve to protect the nasal mucosal surface by mucus secretion, vasodilatation, and sneezing, can be initiated by a variety of stimuli, including allergen, cold air, and chemical irritation. Activation of nasal afferent nerves can also have profound effects on respiration, heart rate, blood pressure, and airway caliber (the diving response). Dysregulation of the nerves in the nose plays an integral role in the pathogenesis of allergic rhinitis. Axon reflexes can precipitate inflammatory responses in the nose, resulting in plasma extravasation and inflammatory cell recruitment, while allergic inflammation can produce neuronal hyper-responsivenesss. Targeting the neuronal dysregulation in the nose may be beneficial in treating upper airway disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Baraniuk JN: Neural control of human nasal secretion. Pulm Pharmacol 1991, 4:20–31.

    Article  PubMed  CAS  Google Scholar 

  2. Stjarne P, Rinder J, Heden-Blomquist E, et al.: Capsaicin desensitization of the nasal mucosa reduces symptoms upon allergen challenge in patients with allergic rhinitis. Acta Otolaryngol 1998, 118:235–239.

    Article  PubMed  CAS  Google Scholar 

  3. Intranasal anticholinergic treatment of nasal disorders. J. Allergy Clin. Immunol 1992, 90:1041-1086.

  4. Allergic rhinitis and its impact on asthma. Workshop Report. J Allergy Clin. Immunol 2001, 108:S147-S333. This workshop report offers a comprehensive overview of the pathogenesis and treatment of allergic rhinitis and its potential influence on asthma.

  5. Baroody FM, Ford S, Lichtenstein LM, et al.: Physiologic responses and histamine release after nasal antigen challenge. Effect of atropine. Am J Respir Crit Care Med 1994, 149:1457–1465.

    PubMed  CAS  Google Scholar 

  6. Togias A, Naclerio RM, Proud D, et al.: Studies on the allergic and nonallergic nasal inflammation. J Allergy Clin Immunol 1988, 81:782–790.

    Article  PubMed  CAS  Google Scholar 

  7. Casale TB: Anti-immunoglobulin e (omalizumab) therapy in seasonal allergic rhinitis. Am J Respir Crit Care Med 2001, 164:S18-S21.

    PubMed  CAS  Google Scholar 

  8. Baroody FM, Naclerio RM: Antiallergic effects of H1-receptor antagonists. Allergy 2000, 55:17–27.

    Article  PubMed  Google Scholar 

  9. Meltzer EO, Malmstrom K, Lu S, et al.: Concomitant montelukast and loratadine as treatment for seasonal allergic rhinitis: a randomized, placebo-controlled clinical trial. J Allergy Clin Immunol 2000, 105:917–922.

    Article  PubMed  CAS  Google Scholar 

  10. Baraniuk JN, Silver PB, Kaliner MA, Barnes PJ: Perennial rhinitis subjects have altered vascular, glandular, and neural responses to bradykinin nasal provocation. Int Arch Allergy Immunol 1994, 103:202–208.

    Article  PubMed  CAS  Google Scholar 

  11. Riccio MM, Proud D: Evidence that enhanced nasal reactivity to bradykinin in patients with symptomatic allergy is mediated by neural reflexes. J Allergy Clin Immunol 1996, 97:1252–1263. This paper provides clear evidence for neuronal hyper-responsiveness associated with allergic inflammation produced by allergic rhinitis.

    Article  PubMed  CAS  Google Scholar 

  12. Sanico AM, Philip G, Proud D, et al.: Comparison of nasal mucosal responsiveness to neuronal stimulation in non-allergic and allergic rhinitis: effects of capsaicin nasal challenge. Clin Exp Allergy 1998, 28:92–100.

    Article  PubMed  CAS  Google Scholar 

  13. Sanico AM, Atsuta S, Proud D, Togias A: Dose-dependent effects of capsaicin nasal challenge: in vivo evidence of human airway neurogenic inflammation. J Allergy Clin Immunol 1997, 100:632–641.

    Article  PubMed  CAS  Google Scholar 

  14. Baraniuk JN, Ali M, Yuta A, et al.: Hypertonic saline nasal provocation stimulates nociceptive nerves, substance P release, and glandular mucous exocytosis in normal humans. Am J Respir Crit Care Med 1999, 160:655–662. This paper demonstrates the potential role of the axon reflex in rhinitis.

    PubMed  CAS  Google Scholar 

  15. Kratschmer F: On reflexes from the nasal mucous membrane on respiration and circulation. Respir Physiol 2001, 127:93–104. This paper, originally published in German in 1870, came from the lab of Ewald Hering in Vienna, a pioneering scientist who facilitated discovery of several reflexes of the upper and lower airways. The paper provides clear evidence for the profound influence nasal afferent nerves have on cardiorespiratory function, and provides definitive evidence for the role of trigeminal afferent nerves in these reflex responses.

    Article  PubMed  CAS  Google Scholar 

  16. Stjarne P, Lundblad L, Anggard A, et al.: Tachykinins and calcitonin gene-related peptide: co-existence in sensory nerves of the nasal mucosa and effects on blood flow. Cell Tissue Res 1989, 256:439–446.

    Article  PubMed  CAS  Google Scholar 

  17. Hunter DD, Dey RD: Identification and neuropeptide content of trigeminal neurons innervating the rat nasal epithelium. Neuroscience 1998, 83:591–599.

    Article  PubMed  CAS  Google Scholar 

  18. Canning BJ, Widdicombe JG: Innervation of the airways. Respir Physiol 2001, 125:1–154.

    Article  PubMed  CAS  Google Scholar 

  19. Stjarne P, Lundblad L, Lundberg JM, Anggard A: Capsaicin and nicotine-sensitive afferent neurones and nasal secretion in healthy human volunteers and in patients with vasomotor rhinitis. Br J Pharmacol 1989, 96:693–701.

    PubMed  CAS  Google Scholar 

  20. McCulloch PF, Panneton WM: Fos immunohistochemical determination of brainstem neuronal activation in the muskrat after nasal stimulation. Neuroscience 1997, 78(3):913–925.

    Article  PubMed  CAS  Google Scholar 

  21. Lacroix JS, Auberson S, Morel DR, et al.: Vascular control of the pig nasal mucosa: distribution and effect of somatostatin in relation to noradrenaline and neuropeptide Y. Regul Pept 1992, 40:373–387.

    Article  PubMed  CAS  Google Scholar 

  22. Hanazawa T, Tanaka K, Chiba T, Konno A: Distribution and origin of nitric oxide synthase-containing nerve fibers in human nasal mucosa. Acta Otolaryngol 1997, 117:735–737.

    PubMed  CAS  Google Scholar 

  23. Revington M, Lacroix JS, Potter EK: Sympathetic and parasympathetic interaction in vascular and secretory control of the nasal mucosa in anaesthetized dogs. J Physiol 1997, 505:823–831.

    Article  PubMed  CAS  Google Scholar 

  24. Lacroix JS, Potter EK, McLachlan E: Nitric oxide and parasympathetic vascular and secretory control of the dog nasal mucosa. Acta Otolaryngol 1998, 118:257–263.

    Article  PubMed  CAS  Google Scholar 

  25. Kondo T, Inokuchi T, Ohta K, et al.: Distribution, chemical coding and origin of nitric oxide synthase-containing nerve fibres in the guinea pig nasal mucosa. J Auton Nerv Syst 2000, 80:71–79.

    Article  PubMed  CAS  Google Scholar 

  26. Baraniuk JN, Lundgren JD, Okayama M, et al.: Vasoactive intestinal peptide in human nasal mucosa. J Clin Invest 1990, 86:825–831.

    PubMed  CAS  Google Scholar 

  27. Baraniuk JN, Lundgren JD, Okayama M, et al.: Substance P and neurokinin A in human nasal mucosa. Am J Respir Cell Mol Biol 1991, 4:228–236.

    PubMed  CAS  Google Scholar 

  28. Baraniuk JN, Silver PB, Kaliner MA, Barnes PJ: Neuropeptide Y is a vasoconstrictor in human nasal mucosa. J Appl Physiol 1992, 73:1867–1872.

    PubMed  CAS  Google Scholar 

  29. Mullol J, Raphael GD, Lundgren JD, et al.: Comparison of human nasal mucosal secretion in vivo and in vitro. J Allergy Clin Immunol 1992, 89:584–592.

    Article  PubMed  CAS  Google Scholar 

  30. Mullol J, Rieves RD, Baraniuk JN, et al.: The effects of neuropeptides on mucous glycoprotein secretion from human nasal mucosa in vitro. Neuropeptides 1992, 21:231–238.

    Article  PubMed  CAS  Google Scholar 

  31. Takeda M, Matsumoto S, Tanimoto T: C-Fos-like immunoreactivity in the upper cervical spinal dorsal horn neurons following noxious chemical stimulation of the nasal mucosa in pentobarbital-anesthetized rats. Arch Histol Cytol 1998, 61:83–87.

    PubMed  CAS  Google Scholar 

  32. Anton F, Herdegen T, Peppel P, Leah JD: c-FOS-like immunoreactivity in rat brainstem neurons following noxious chemical stimulation of the nasal mucosa. Neuroscience 1991, 41:629–641.

    Article  PubMed  CAS  Google Scholar 

  33. Suzuki N, Hardebo JE, Owman C: Trigeminal fibre collaterals storing substance P and calcitonin gene-related peptide associate with ganglion cells containing choline acetyltransferase and vasoactive intestinal polypeptide in the sphenopalatine ganglion of the rat. An axon reflex modulating parasympathetic ganglionic activity? Neuroscience 1989, 30:595–604.

    Article  PubMed  CAS  Google Scholar 

  34. Riccio MM, Reynolds CJ, Hay DW, Proud D: Effects of intranasal administration of endothelin-1 to allergic and nonallergic individuals. Am J Respir Crit Care Med 1995, 152:1757–1764.

    PubMed  CAS  Google Scholar 

  35. Figueroa JM, Mansilla E, Suburo AM: Innervation of nasal turbinate blood vessels in rhinitic and nonrhinitic children. Am J Respir Crit Care Med 1998, 157:1959–1966. This paper presents evidence that the mucosa of rhinitic patients become hyperinnervated.

    PubMed  CAS  Google Scholar 

  36. Hunter DD, Satterfield BE, Huang J, et al.: Toluene diisocyanate enhances substance P in sensory neurons innervating the nasal mucosa. Am J Respir Crit Care Med 2000, 161:543–549.

    PubMed  CAS  Google Scholar 

  37. Undem BJ, Carr MJ: Pharmacology of airway afferent nerve activity. Respir Res 2001, 2:234–244.

    Article  PubMed  CAS  Google Scholar 

  38. Bradding P, Mediwake R, Feather IH, et al.: TNF alpha is localized to nasal mucosal mast cells and is released in acute allergic rhinitis. Clin Exp Allergy 1995, 25:406–415.

    Article  PubMed  CAS  Google Scholar 

  39. Woolf CJ, Allchorne A, Safieh-Garabedian B, Poole S: Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumour necrosis factor alpha. Br J Pharmacol 1997, 121:417–424.

    Article  PubMed  CAS  Google Scholar 

  40. Oh SB, Tran PB, Gillard SE, et al.: Chemokines and glycoprotein120 produce pain hypersensitivity by directly exciting primary nociceptive neurons. J Neurosci 2001, 21:5027–5035.

    PubMed  CAS  Google Scholar 

  41. Lee LY, Gu Q, Gleich GJ: Effects of human eosinophil granule-derived cationic proteins on C-fiber afferents in the rat lung. J Appl Physiol 2001, 91:1318–1326.

    PubMed  CAS  Google Scholar 

  42. Erjefalt JS, Greiff L, Andersson M, et al.: Allergen-induced eosinophil cytolysis is a primary mechanism for granule protein release in human upper airways. Am J Respir Crit Care Med 1999, 160:304–312.

    PubMed  CAS  Google Scholar 

  43. Carr MJ, Hunter DD, Undem BJ: Neurotrophins and asthma. Curr Opin Pulm Med 2001, 7:1–7. A comprehensive review of the emerging appreciation of the potential role of neurotrophins in airways diseases.

    Article  PubMed  CAS  Google Scholar 

  44. Bonini S, Lambiase A, Bonini S, et al.: Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma. Proc Natl Acad Sci U S A 1996, 93:10955–10960.

    Article  PubMed  CAS  Google Scholar 

  45. Virchow JC, Julius P, Lommatzsch M, et al.: Neurotrophins are increased in bronchoalveolar lavage fluid after segmental allergen provocation. Am J Respir Crit Care Med 1998, 158:2002–2005.

    PubMed  CAS  Google Scholar 

  46. Sanico AM, Stanisz AM, Gleeson TD, et al.: Nerve growth factor expression and release in allergic inflammatory disease of the upper airways. Am J Respir Crit Care Med 2000, 161:1631–1635.

    PubMed  CAS  Google Scholar 

  47. Hoyle GW, Graham RM, Finkelstein JB, et al.: Hyperinnervation of the airways in transgenic mice overexpressing nerve growth factor. Am J Respir Cell Mol Biol 1998, 18:149–157.

    PubMed  CAS  Google Scholar 

  48. Fischer A, McGregor GP, Saria A, et al.: Induction of tachykinin gene and peptide expression in guinea pig nodose primary afferent neurons by allergic airway inflammation. J Clin Invest 1996, 98:2284–2291.

    PubMed  CAS  Google Scholar 

  49. Hunter DD, Myers AC, Undem BJ: Nerve growth factorinduced phenotypic switch in guinea pig airway sensory neurons. Am J Respir Crit Care Med 2000, 161:1985–1990.

    PubMed  CAS  Google Scholar 

  50. Black PN, Ghatei MA, Takahashi K, et al.: Formation of endothelin by cultured airway epithelial cells. FEBS Lett 1989, 255:129–132.

    Article  PubMed  CAS  Google Scholar 

  51. Nan B, Getchell ML, Partin JV, Getchell TV: Leukemia inhibitory factor, interleukin-6, and their receptors are expressed transiently in the olfactory mucosa after target ablation. J Comp Neurol 2001, 435:60–77.

    Article  PubMed  CAS  Google Scholar 

  52. Einarsson O, Geba GP, Zhu Z, et al.: Interleukin-11: stimulation in vivo and in vitro by respiratory viruses and induction of airways hyperresponsiveness. J Clin Invest 1996, 97:915–924.

    Article  PubMed  CAS  Google Scholar 

  53. Sant’Ambrogio G, Tsubone H, Sant’Ambrogio FB: Sensory information from the upper airway: role in the control of breathing. Respir Physiol 1995, 102:1–16.

    Article  PubMed  CAS  Google Scholar 

  54. Togias A: Mechanisms of nose-lung interaction. Allergy 1999, 54(Suppl 57):94–105.

    PubMed  Google Scholar 

  55. Gastroesophageal Reflux Disease and Airway Disease. Edited by Stein, MR. New York: Marcel Dekker; 1999.

  56. Irwin RS, Madison JM: The diagnosis and treatment of cough. N Engl J Med 2000, 343:1715–1721.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Canning, B.J. Neurology of allergic inflammation and rhinitis. Curr Allergy Asthma Rep 2, 210–215 (2002). https://doi.org/10.1007/s11882-002-0021-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-002-0021-2

Keywords

Navigation