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Updated: Apr 17, 2026
Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
Published on: October 16, 2013
Transient receptor potential A1 activation prolongs isoflurane induction latency and impairs respiratory function in
Fengxian Li1, Changxiong J Guo, Cheng-Chiu Huang
1From the Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri (F.L., C.J.G., C.-C.H., G.Y., Q.L.); Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China (F.L., S.X.); School of Basic Medical Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China (G.Y.); and Departments of Pediatrics, Anesthesiology, and Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, Missouri (S.M.B.).
Background:
Isoflurane is a potent volatile anesthetic; however, it evokes airway irritation and neurogenic constriction through transient receptor potential (TRP) A1 channels and sensitizes TRPV1 channels, which colocalizes with TRPA1 in most of the vagal C-fibers innervating the airway. However, little is known about the precise effects of these two channels on the respiratory function during isoflurane anesthesia.
Methods:
By using a rodent behavioral model and whole-body plethysmograph, the authors examined the response of Trpa1 and Trpv1 mice to isoflurane anesthesia and monitored their respiratory functions during anesthesia.
Results:
This study showed that Trpa1 mice (n = 9), but not Trpv1 mice (n = 11), displayed a shortened induction latency compared with wild-type mice (n = 10) during isoflurane anesthesia (33 ± 2.0 s in wild-type and 33 ± 3.8 s in Trpv1 vs. 17 ± 1.8 in Trpa1 at 2.2 minimum alveolar concentrations). By contrast, their response to the nonpungent volatile anesthetic sevoflurane is indistinguishable from wild-type mice (24 ± 3.6 s in wild-type vs. 26 ± 1.0 s in Trpa1 at 2.4 minimum alveolar concentrations). The authors discovered that Trpa1 mice inhaled more anesthetic but maintained better respiratory function. Further respiration pattern analysis revealed that isoflurane triggered nociceptive reflexes and led to prolonged resting time between breaths during isoflurane induction as well as decreased dynamic pulmonary compliance, an indicator of airway constriction, throughout isoflurane anesthesia in wild-type and Trpv1 mice, but not in Trpa1 mice.
Conclusion:
Activation of TRPA1 by isoflurane negatively affects anesthetic induction latency by altering respiratory patterns and impairing pulmonary compliance.
