Capsaicin-induced mucus secretion in rat airways assessed in vivo and non-invasively by magnetic resonance imaging.
OBJECTIVE
An up-regulation of the sensory neural pathways in the lung has been implicated in asthma and chronic obstructive pulmonary disease (COPD) and is thought to contribute to mucus hypersecretion, an essential feature of both diseases. The aim of this study was to assess non-invasively the acute effects (up to 60 min) of sensory nerve stimulation by capsaicin in the lung, using magnetic resonance imaging (MRI).


METHODS
Male Brown Norway rats were imaged prior to and 10, 30 and 60 min after intra-tracheal challenge with capsaicin (30 microg kg(-1)) or vehicle (0.5% ethanol solution). In subsequent studies, pre-treatment with the transient receptor potential vanilloid (TRPV)-1 antagonist, capsazepine; the dual neurokinin (NK) 1 and NK2 receptor antagonist, DNK333 and the mast cell stabilizer, di-sodium cromoglycate (DSCG) was used to modulate the effects of capsaicin.


RESULTS
Diffuse fluid signals were detected by MRI in the lung as early as 10 min after capsaicin, remaining constant 30 and 60 min after treatment. Broncho-alveolar lavage (BAL) fluid analysis performed 60 min after capsaicin revealed increased mucin concentration. Capsazepine (3.5 mg kg(-1)), DNK333 (10 mg kg(-1)) but not DSCG (10 mg kg(-1)) administered prophylactically were able to block the effect of capsaicin in the airways.


CONCLUSIONS
These observations suggest that the fluid signals detected by MRI after capsaicin administration reflected predominantly the release of mucus following activation of sensory nerves. They point to the opportunity of non-invasively assessing with MRI the influence of neuronal mechanisms in animal models of asthma and COPD.
Karmouty-Quintana
H
H
Discovery Technologies, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Cannet
C
C
Sugar
R
R
Fozard
J R
JR
Page
C P
CP
Beckmann
N
N
D000818:Animals; D001372:Aza Compounds / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004205:Cromolyn Sodium / Q000494:pharmacology; D020397:Goblet Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009093:Mucus / Q000378:metabolism*; D009475:Neurons, Afferent / Q000187:drug effects*; D051381:Rats; D011914:Rats, Inbred BN; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000187:drug effects / Q000378:metabolism; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D001372:Aza Compounds; D001549:Benzamides; C448383:DNK 333; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C071423:capsazepine; D004205:Cromolyn Sodium; D002211:Capsaicin