Imaging activity in nerves that mediate pain from gastrointestinal organs
Peter Lipták1, Nikoleta Pavelková2,3, Jana Harsányiová2,3, Peter Bánovčin Jr1, Marián Kollárik3
1 Interná klinika gastroenterologická JLF UK a UN Martin, Slovenská republika
2 Ústav patologickej fyziológie, JLF UK v Bratislave, Slovenská republika
3 Department of Molecular Pharmacology & Physiology, Morsani Col lege of Medicine, University of South Florida, USA
Background: Visceral afferent nerves project from internal organs and provide information to the central nervous system. The role of afferent nerves in the pathogenesis and symptoms of gastrointestinal diseases is often underappreciated. Nonetheless, pain, heartburn, fullness, nausea, and vomiting are all mediated by visceral afferent nerves. Furthermore, stimulation of visceral afferent nerves by inflammation in diseases disrupts the normal regulation of gastrointestinal secretion and motility, thereby contributing to symptoms ranging from dysphagia to diarrhea and constipation. Thus, therapeutic targeting of visceral afferent nerves may aid the treatment of many gastrointestinal diseases. However, the development of novel drugs targeting visceral afferent nerves is hindered by the limited knowledge of these nerves. For example, the identities of the acid receptors in esophageal nerves that cause heartburn and the ion channels responsible for mechanical activation in nerves that mediate colic pain have not been fully elucidated. The limited knowledge of visceral afferent nerves is largely attributable to difficulties associated with their study; only one nerve fiber can typically be studied at a time by classical electrophysiology. Purpose: Here, we report the adaptation of a cutting-edge high-throughput method to study gastrointestinal afferent nerves that allows the activity in hundreds of neurons to be imaged simultaneously. This method is based on genetic expression of the fluorescent calcium indicator GCaMP6 and multiphoton microscopy in transgenic mice. In addition to providing fundamental information about visceral afferent nerves, future iterations of this method are expected to enable studies of nerve activity in biopsies from patients with gastrointestinal diseases.
Keywordspain, gastrointestinal tract, innervation, microscopy
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