A critical re‐evaluation of the specificity of action of perivagal capsaicin

• Published in: The Journal of physiology Vol. 591; no. 6; pp. 1563 - 1580
• Main Authors: Browning, K. N., Babic, T., Holmes, G. M., Swartz, E., Travagli, R. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2013; Wiley Subscription Services, Inc; Blackwell Science Inc
• Subjects: Action Potentials - drug effects; Animals; Brain Stem - metabolism; Brain Stem - physiology; Calcium - metabolism; Capsaicin - pharmacology; Choline O-Acetyltransferase - genetics; Choline O-Acetyltransferase - metabolism; Dendrites - physiology; Gastrointestinal Motility - drug effects; Gene Expression - drug effects; Integrative; Motor Neurons - physiology; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase - metabolism; Potassium - metabolism; Rats; Rats, Sprague-Dawley; Thyrotropin-Releasing Hormone - pharmacology; Vagotomy; Vagus Nerve - drug effects; Vagus Nerve - metabolism; Vagus Nerve - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2012.246827

Key points Perivagal application of capsaicin (1% solution) is considered to cause selective degeneration of vagal afferent (sensory) C fibres and has been used extensively to examine the site of action of many gastrointestinal (GI) neuropeptides. The actions of both capsaicin and GI neuropeptides may not be restricted to vagal afferent fibres, however, as other non‐sensory neurones displayed sensitivity to capsaicin and brainstem microinjections of these neuropeptides induce GI effects similar to those obtained upon systemic application. The present study used immunohistochemical, biophysical and functional approaches to test the hypothesis that perivagal capsaicin induces degeneration of vagal efferents controlling GI functions. Our data indicate that perivagal application of capsaicin induces degeneration of vagal efferent motoneurones and decreased vagal motor responses. Treatment with perivagal capsaicin cannot therefore be considered selective for vagal afferent C fibres and, consequently, care is needed when using perivagal capsaicin to assess the mechanism of action of GI neuropeptides.   Perivagal application of capsaicin (1% solution) is considered to cause a selective degeneration of vagal afferent C fibres and has been used extensively to examine the site of action of many gastrointestinal (GI) neuropeptides. The actions of both capsaicin and GI neuropeptides may not be restricted to vagal afferent fibres, however, as other non‐sensory neurones have displayed sensitivity to capsaicin and brainstem microinjections of these neuropeptides induce GI effects similar to those obtained upon systemic application. The aim of the present study was to test the hypothesis that perivagal capsaicin induces degeneration of vagal efferents controlling GI functions. Experiments were conducted 7–14 days after 30 min unilateral perivagal application of 0.1–1% capsaicin. Immunohistochemical analyses demonstrated that, as following vagotomy, capsaicin induced dendritic degeneration, decreased choline acetyltransferase but increased nitric oxide synthase immunoreactivity in rat dorsal motor nucleus of the vagus (DMV) neurones. Electrophysiological recordings showed a decreased DMV input resistance and excitability due, in part, to the expression of a large conductance calcium‐dependent potassium current and the opening of a transient outward potassium window current at resting potential. Furthermore, the number of DMV neurones excited by thyrotrophin‐releasing hormone and the gastric motility response to DMV microinjections of TRH were decreased significantly. Our data indicate that perivagal application of capsaicin induced DMV neuronal degeneration and decreased vagal motor responses. Treatment with perivagal capsaicin cannot therefore be considered selective for vagal afferent C fibres and, consequently, care is needed when using perivagal capsaicin to assess the mechanism of action of GI neuropeptides.