To the Editor:

Recent discoveries in the mechanism of action of ragweed sensitivity may have a bearing on the choice of anesthetic agent. We review some pathways that affect bronchial motor tone and how they may influence the choice of anesthetic agent. Bronchial motor tone is regulated by the parasympathetic nervous system, which exerts a contractile action through activation of M3 receptors, and by the nonadrenergic noncholinergic pathways having both inhibitory and excitatory effects. The bronchial response to stimulation is in part due to C-fibers in the bronchial wall that are responsible for a local axon reflex, with irritant stimulation of nerve endings leading to the release of bronchoconstricting tachykinins such as substance P, neurokinin A, and calcitonin gene-related peptide.1,2  While sevoflurane does not induce increased airway resistance, desflurane-elicited airway constriction appears to be mediated by the release of these tachykinins.3 

The transient receptor potential (TRP) family of cation channels is highly expressed by a subset of C-fiber nociceptors, including those in the lung.4,5  TRPA1 is expressed in sensory neurons, and colocalizes with TRPV1, calcitonin gene-related peptide, substance P, and bradykinin receptors.6  TRPA1 is activated by the pungent ingredients in mustard and garlic extracts, allyl isothiocyanate 7  and allicin.8  Sensory neurons from TRPA1-deficient mice show greatly diminished responses to each of these compounds, demonstrating that the TRPA1 channel is the primary molecular site by which they activate the irritant and pain pathway,9,10  as well as initiate the asthmatic airway inflammation.11  TRPA1 receptors are activated by desflurane and isoflurane,3,7,12  similar to the effects of several air pollutants and chemicals that cause airway constriction, such as αβ-unsaturated aldehydes and acrolein that activate the axon reflex release of tachykinins.8,13 

It has been recently reported that the TRPA1 receptor is also activated by the sesquiterpenoids present in the pollen from common ragweed (Ambrosia artemisiifolia), and activation of this receptor may contribute to the various respiratory symptoms caused by inhalation of this pollen.14  The sensitivity of a patient to ragweed suggests enhanced response of the TRPA1-activated tachykinin pathway. This sensitivity may have implications for anesthetic choice in patients with allergy to ragweed and possibly other pollens. Activation of TRPA1 by desflurane and isoflurane may be more likely in this setting of heightened sensitivity, leading to increased airway resistance and decreased lung compliance15  as well as causing bronchospasm and cough.16,17  These effects may in part be counteracted by volatile anesthetics’ ability to directly relax airway smooth muscle18  and by desensitization of the TRPA1 receptor during sustained exposure.19  Nevertheless, the activation of TRPA1 receptors in the upper airway has been suggested to be in part responsible for the clinical observation of cough and laryngospasm due to desflurane.3,4,13 

The role of TRPA1 receptor in irritant-induced cough and increased airway resistance and their stimulation by desflurane and isoflurane could account for some of the clinical side effects of these drugs. Clinicians may want to take these findings into consideration when choosing an anesthetic for their patients. The lack of stimulation of TRPA1 receptors by sevoflurane3,12  may explain its relative lack of irritation16,17  and make it a less irritating choice in patients who have demonstrated heightened airway sensitivity to ragweed pollen or other chemical irritants.

1.
Canning
BJ
:
Reflex regulation of airway smooth muscle tone.
J Appl Physiol
2006
;
101
:
971
85
2.
Lamb
JP
,
Sparrow
MP
:
Three-dimensional mapping of sensory innervation with substance P in porcine bronchial mucosa: Comparison with human airways.
Am J Respir Crit Care Med
2002
;
166
:
1269
81
3.
Satoh
J
,
Yamakage
M
:
Desflurane induces airway contraction mainly by activating transient receptor potential A1 of sensory C-fibers.
J Anesth
2009
;
23
:
620
3
4.
Nassenstein
C
,
Kwong
K
,
Taylor-Clark
T
,
Kollarik
M
,
Macglashan
DM
,
Braun
A
,
Undem
BJ
:
Expression and function of the ion channel TRPA1 in vagal afferent nerves innervating mouse lungs.
J Physiol (Lond)
2008
;
586
:
1595
604
5.
Banner
KH
,
Igney
F
,
Poll
C
:
TRP channels: Emerging targets for respiratory disease.
Pharmacol Ther
2011
;
130
:
371
84
6.
Chen
J
,
Joshi
SK
,
DiDomenico
S
,
Perner
RJ
,
Mikusa
JP
,
Gauvin
DM
,
Segreti
JA
,
Han
P
,
Zhang
XF
,
Niforatos
W
,
Bianchi
BR
,
Baker
SJ
,
Zhong
C
,
Simler
GH
,
McDonald
HA
,
Schmidt
RG
,
McGaraughty
SP
,
Chu
KL
,
Faltynek
CR
,
Kort
ME
,
Reilly
RM
,
Kym
PR
:
Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation.
Pain
2011
;
152
:
1165
72
7.
Eilers
H
,
Cattaruzza
F
,
Nassini
R
,
Materazzi
S
,
Andre
E
,
Chu
C
,
Cottrell
GS
,
Schumacher
M
,
Geppetti
P
,
Bunnett
NW
:
Pungent general anesthetics activate transient receptor potential-A1 to produce hyperalgesia and neurogenic bronchoconstriction.
Anesthesiology
2010
;
112
:
1452
63
8.
Bautista
DM
,
Jordt
SE
,
Nikai
T
,
Tsuruda
PR
,
Read
AJ
,
Poblete
J
,
Yamoah
EN
,
Basbaum
AI
,
Julius
D
:
TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents.
Cell
2006
;
124
:
1269
82
9.
Kwan
KY
,
Allchorne
AJ
,
Vollrath
MA
,
Christensen
AP
,
Zhang
DS
,
Woolf
CJ
,
Corey
DP
:
TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction.
Neuron
2006
;
50
:
277
89
10.
McNamara
CR
,
Mandel-Brehm
J
,
Bautista
DM
,
Siemens
J
,
Deranian
KL
,
Zhao
M
,
Hayward
NJ
,
Chong
JA
,
Julius
D
,
Moran
MM
,
Fanger
CM
:
TRPA1 mediates formalin-induced pain.
Proc Natl Acad Sci USA
2007
;
104
:
13525
30
11.
Caceres
AI
,
Brackmann
M
,
Elia
MD
,
Bessac
BF
,
del Camino
D
,
D’Amours
M
,
Witek
JS
,
Fanger
CM
,
Chong
JA
,
Hayward
NJ
,
Homer
RJ
,
Cohn
L
,
Huang
X
,
Moran
MM
,
Jordt
SE
:
A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma.
Proc Natl Acad Sci USA
2009
;
106
:
9099
104
12.
Matta
JA
,
Cornett
PM
,
Miyares
RL
,
Abe
K
,
Sahibzada
N
,
Ahern
GP
:
General anesthetics activate a nociceptive ion channel to enhance pain and inflammation.
Proc Natl Acad Sci USA
2008
;
105
:
8784
9
13.
Geppetti
P
,
Patacchini
R
,
Nassini
R
,
Materazzi
S
:
Cough: The emerging role of the TRPA1 channel.
Lung
2010
;
188
(
suppl 1
):
S63
8
14.
Taglialatela-Scafati
O
,
Pollastro
F
,
Minassi
A
,
Chianese
G
,
De Petrocellis
L
,
Di Marzo
V
,
Appendino
G
:
Sesquiterpenoids from common ragweed (Ambrosia artemisiifolia L.), an invasive biological polluter.
Eur J Org Chem
2012
;
2012
:
5162
70
15.
von Ungern-Sternberg
BS
,
Saudan
S
,
Petak
F
,
Hantos
Z
,
Habre
W
:
Desflurane but not sevoflurane impairs airway and respiratory tissue mechanics in children with susceptible airways.
Anesthesiology
2008
;
108
:
216
24
16.
Klock
PA
Jr
,
Czeslick
EG
,
Klafta
JM
,
Ovassapian
A
,
Moss
J
:
The effect of sevoflurane and desflurane on upper airway reactivity.
Anesthesiology
2001
;
94
:
963
7
17.
Arain
SR
,
Shankar
H
,
Ebert
TJ
:
Desflurane enhances reactivity during the use of the laryngeal mask airway.
Anesthesiology
2005
;
103
:
495
9
18.
Mazzeo
AJ
,
Cheng
EY
,
Bosnjak
ZJ
,
Coon
RL
,
Kampine
JP
:
Differential effects of desflurane and halothane on peripheral airway smooth muscle.
Br J Anaesth
1996
;
76
:
841
6
19.
Raisinghani
M
,
Zhong
L
,
Jeffry
JA
,
Bishnoi
M
,
Pabbidi
RM
,
Pimentel
F
,
Cao
D-S
,
Evans
MS
,
Premkumar
LS
:
Activation characteristics of transient receptor potential ankyrin 1 and its role in nociception.
Am J Physiol Cell Physiol
2011
;
301
:
C587
600