title: Desflurane but not sevoflurane augments laryngeal C-fiber inputs to nucleus tractus solitarii neurons by activating transient receptor potential-A1.
abstract: OBJECTIVE
  Volatile anesthetics have distinct odors and some are irritating to the upper airway and may cause cough and laryngospasm, which may result, in part, from stimulation of C-fiber reflex. Local exposure of such anesthetics increases the sensitivity of capsaicin-sensitive laryngeal C-fiber endings compatible with airway irritability presumably by activation of transient receptor potential (TRP) ion channels, but the physiological relevance of this sensitization transmitted to the higher-order neurons in the central reflex pathway and output is unknown.
  
  
  METHODS
  In anesthetized young guinea pigs, baseline and left atrial capsaicin evoked changes in the extracellular unit activity of laryngeal C-fiber-activated neurons in the nucleus tractus solitarii (NTS) and phrenic nerve activity were compared between irritant (desflurane) and non-irritant (sevoflurane) anesthetic gas exposure to the isolated larynx.
  
  
  RESULTS
  Desflurane significantly augmented the peak and duration (p<0.01) of the NTS neuronal responses and the prolongation of expiratory time (p=0.017). The effect was enhanced by iontophoretic application of the TRPA1 agonist allyl-isothiocyanate (p<0.05), inhibited by TRPA1 antagonist HC-030031 (p<0.01), but not by TRPV1 antagonist BCTC. Sevoflurane did not affect the central pathway.
  
  
  CONCLUSIONS
  Thus, the sensitization of the laryngeal C-fiber endings by irritant volatile anesthetics is transmitted to the NTS via activation of the TRPA1 and is associated with a prolonged reflexively evoked expiratory apnea. The findings may help to explain local deleterious effects of irritant volatile general anesthetics on the airways during inhaled induction or bronchodilator therapy for status asthmatics.
authors.affiliation: Department of Surgical Neurology, Research Institute for Brain and Blood Vessels-AKITA, Akita, Japan. tmutoh@tiara.ocn.ne.jp
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Mutoh
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Taki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tsubone
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D000077335:Desflurane; D006168:Guinea Pigs; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D017879:Isothiocyanates / Q000494:pharmacology; D007823:Laryngeal Nerves / Q000187:drug effects / Q000378:metabolism; D007830:Larynx / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011687:Purines / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D000077149:Sevoflurane; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D050051:Transient Receptor Potential Channels / Q000187:drug effects* / Q000378:metabolism
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D018685:Anesthetics, Inhalation; D017879:Isothiocyanates; D008738:Methyl Ethers; C475772:N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide; D011687:Purines; D011719:Pyrazines; D011725:Pyridines; D050051:Transient Receptor Potential Channels; D000077149:Sevoflurane; C004471:allyl isothiocyanate; D000077335:Desflurane; D007530:Isoflurane; D002211:Capsaicin