The function of vagal nociceptors in the esophagus
Comenius University Martin
Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius University
Prof. Milos Tatar, MD. CSc.
Associate Prof. Marian Kollarik, MD. PhD.
4 weeks
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
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Type of Research Project
- Basic science
What is the background of the project?
Diseases of the esophagus present an important health and social burden, but the neural mechanisms of the esophageal pain/heartburn and reflex dysregulation of the esophagus are incompletely understood. Our group recently discovered that in addition to traditionally described low threshold mechanosensors, the vagal afferent innervation of the esophagus consists also of large populations of nociceptors. The vagal esophageal nociceptors selectively detect noxious physical, chemical and inflammatory stimuli relevant for esophageal pathophysiology, and likely critically contribute to esophageal nociception and reflex responses to tissue inflammation and damage. However, this role of vagal esophageal nociceptors has not been established and their function is at present unknown. During my training at Johns Hopkins University I developed and evaluated novel techniques for acute and chronic noxious mechanical and chemical stimulation of the esophagus in animal models. I also adapted methods essential for the study of nociceptive function including in vivo virus vector-delivered shRNA silencing-mediated selective inhibition of vagal nerves and evaluation of the nocicefensive behavior. I aim to utilize this expertise to advance the understanding of the role of vagal nociceptors in esophageal sensations and reflex regulation of the esophagus. This knowledge is predicted to aid the identification of novel neural drug targets for treatment of visceral pain and neural dysregulation.
What is the aim of the project?
The aim of the project: 1. To evaluate the role of vagal esophageal nociceptive subtypes in acute nocifensive responses evoked by noxious mechanical and chemical stimulation of the esophagus. 2. To evaluate the role of vagal esophageal nociceptive subtypes in selected reflexes influencing the gastroesophageal reflux. In order to evaluate the contribution of vagal and spinal nociceptors to investigated phenomena (nocifensive behavior and selected reflexes) I will use two independent methods for selective inhibition of vagal or spinal nociceptive pathways and their combination: in vivo virus vector-delivered shRNA silencing-mediated selective inhibition of vagal nerves and selective neurotoxic denervation. The results will be corroborated in specific instances by selective stimulation of vagal nociceptive subtypes. ad 1) I will initially focus on the responses evoked by noxious (>100mmHg) distention of the esophagus and the responses evoked by nociceptive activator capsaicin. ad 2) I will initially focus on the non-swallow initiated relaxation of the lower esophageal sphincter evoked by gastric distention as a model of transient LES relaxation (TLESR).
What techniques and methods are used?
electrophysiology methods, patch clamp, PCR, behavioural methods, shRNA virus silencing
What is the role of the student?
What are the tasks expected to be accomplished by the student?
no specific requirement
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
basic laboratory work, physiology of vagal nerve and esophagus, pain physiology and pathophysiology
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts:
- Medical students
- Yu S; Undem BJ; Kollarik M. Vagal afferent nerves with nociceptive properties in guinea- pig oesophagus. J Physiol 2005;563(Pt 3):831-42
- Kollarik M; Carr MJ; Ru F; Ring CJ; Hart VJ; Murdock P; Myers AC; Muroi Y; Undem BJ. Transgene expression and effective gene silencing in vagal afferent neurons in vivo using recombinant adeno-associated virus vectors. J Physiol. 2010 Nov 1;588(Pt 21):4303-15. Epub 2010 Aug 24