POSTСOLITIS ALTERATIONS IN NOCICEPTIVE PROPERTIES OF NEURONS IN THE RAT RAPHE MAGNUS AND DORSAL RAPHE NUCLEI

Abstract

Dysfunction of the brain serotonergic system is thought to play a leading role in the pathogenesis of chronic abdominal pain and comorbid somatic hyperalgesia, which disturb a significant proportion of patients with digestive tract diseases, even in remission. However, the specific changes in the serotonergic structures nociceptive properties that can be initiated by organic pathology and persist after its resolution remain unclear. The aim of our neurophysiological study on anesthetized rats – healthy and recovered from colitis – was to identify the alterations in the raphe magnus (RMg) and dorsal raphe (DR) nuclei neuronal responses to visceral (colorectal distension) and somatic (squeezing of the tail) noxious stimulations that persist after resolution of intestinal inflammation. It has been shown that both nuclei contain different groups of nociceptive neurons: 1) responding with activation only to colorectal distension (visceral); 2) excited only by tail squeezing (somatic); 3) reacting with excitation to the both irritations (general); 4) responding with discharge inhibition to any of the stimulations (inhibited). Compared with healthy animals, in RMg of colitis-exposed rats the number of the inhibited cells was increased and the total proportion of excited nociceptive neurons was reduced. Distension of the inflammation-undergone intestine caused enhanced RMg neuronal inhibition, whereas squeezing of the pathology-unaffected tail led to increased excitation of the RMg selective somatic and general nociceptive cells. In turn, in the DR of postcolitis rats the inhibited neuron proportion was reduced, while the increased population of excited neurons included fewer visceral and more somatic selective cells. This was accompanied by an increase in the selective reactions of the latter to somatic pain stimuli and by an increase in non-selective DR neuron excitation by visceral and somatic pain signals. The identified neuronal alterations can contribute to the postcolitis impairment of the studied raphe nuclei functions in the endogenous control of visceral and somatic pain sensitivity.