Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain

Table 1 The different methods for pain stimulation of the human GI tract

Stimulationmodality	Stimulatedstructures	Advantages	Limitations
Electrical	Nerve fibers primarily in mucosa and muscle layers dependent of the stimulation intensity (not a specific activation of the nociceptors)	Excellent for repeated stimulation, suitable for neurophysiologic assessments of the pain	The electrical threshold depends on the fiber diameter, i.e. small-diameter nerves cannot be excited without exciting others. May induce arrhythmias in areas near the heart
Mechanical	Mechanoreceptors located in different layers	Imitates a bolus, reproducible stimulus	Problems with estimating the transmural pressure and change in circumference
Thermal	Thermal sensitive receptors preferentially in the luminal layers	Activation of unmyelinated afferents in the mucosa selectively	Temperature stimuli in the range that can be felt are normally only relevant for sensation in the upper GI tract.
Chemical	Chemo-sensitive receptors, primarily in the mucosa	Resembles clinical inflammation, chemical stimuli activate predominantly unmyelinated C-fibres	Require a relative long latency time to the onset of effects, and that they are often not reproducible when repeated