title: Irritant volatile anesthetics induce neurogenic inflammation through TRPA1 and TRPV1 channels in the isolated mouse trachea.
abstract: BACKGROUND
  Irritating effects of volatile general anesthetics on tracheal nerve endings and resulting spastic reflexes in the airways are not completely understood with respect to molecular mechanisms. Neuropeptide release and neurogenic inflammation play an established role.
  
  
  METHODS
  The basal and stimulated calcitonin gene-related peptide (CGRP) release from the isolated superfused mouse trachea was analyzed as an index of sensory neuron activation, applying irritant (desflurane and isoflurane) and nonirritant (sevoflurane) volatile anesthetics as stimuli. Various gas concentrations (0.5-, 1-, or 2-fold minimum alveolar concentration [MAC]) and different O2 atmospheres were used for tracheal stimulation at 38°C. Null mutants of the capsaicin receptor TRPV1 and of the chemoreceptor TRPA1, as well as double knockout mice, were used as tissue donors.
  
  
  RESULTS
  Desflurane and, less so, isoflurane caused a concentration-dependent tracheal CGRP release, both saturating at 1 MAC (human), that is, 6% and 1.25%, respectively. With desflurane, the O2 concentration (25% or 94%) did not make a difference. Sevoflurane 1 MAC did not activate tracheal CGRP release. TRPV1 mice showed 75% reduced desflurane responses, and TRPA1 and double-null mutants showed no responses at all.
  
  
  CONCLUSIONS
  Our results confirm the clinical experience that desflurane is more irritating than isoflurane at equal anesthetic gas concentration, whereas sevoflurane does not activate tracheobronchial sensory nerves to release neuropeptides and induce neurogenic inflammation. Both irritant receptor channels, TRPA1 more than TRPV1, are involved in mediating the adverse effects that may even extend to systemic proinflammatory sequelae.
authors.affiliation: From the *Institute of Physiology and Pathophysiology and †Department of Anesthesiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; and ‡Clinic of Anesthesia and Critical Care Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Tatjana I
authors.initials: TI
authors.lastname: Kichko
authors.forename: Florian
authors.initials: F
authors.lastname: Niedermirtl
authors.forename: Andreas
authors.initials: A
authors.lastname: Leffler
authors.forename: Peter W
authors.initials: PW
authors.lastname: Reeh
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D000077335:Desflurane; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced*; D007530:Isoflurane / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009443:Neuritis / Q000139:chemically induced*; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000187:drug effects* / Q000235:genetics; D014132:Trachea / Q000187:drug effects*; D014136:Tracheitis / Q000139:chemically induced*; D050051:Transient Receptor Potential Channels / Q000187:drug effects* / Q000235:genetics
chemical_list: D018685:Anesthetics, Inhalation; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D000077335:Desflurane; D007530:Isoflurane; D015740:Calcitonin Gene-Related Peptide