Neurochemical bases of visceral nociception: mathematical model.

A mathematical model of visceral perception was constructed, comprising primary sensory, motor, intestinofugal and principal neurons, interstitial cells of Cajal and smooth muscle elements that are arranged in a functional circuit through chemical synapses. The mathematical description of constructive elements was based on detailed morphological, anatomical, electrophysiological and neuropharmacological characteristics of cells and chemical processes of electrochemical coupling. Emphasis was given to signal transduction mechanisms that involved multiple neurotransmitters and receptor polymodality. The role of co-transmission by acetylcholine (ACh), serotonin (5-HT), noradrenalin (NA), N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and their corresponding receptors-muscarinic and nicotinic type ACh receptors, beta-adrenoceptors, 5-HT(3/4) type serotonergic receptors, NMDA and AMPA receptors in pathogenesis of nociception was studied numerically. Results of computer simulations reproduced patterns of electrical activity of neurons and mechanical responses of the smooth muscle similar to those observed in in vivo and in vitro experiments when ACh, 5-HT, NA, NMDA and AMPA were acting either alone or co-jointly. The results provide neurochemical bases for explanation of pathophysiological mechanisms of visceral nociception, which cannot be elucidated by existing experimental methods. Care should be taken though when extrapolating the numerical results onto the actual system because of limiting assumptions of the model.