Effects of the Nucleus Raphe Magnus Stimulation on Nociceptive Neurons of the Rat Caudal Ventrolateral Medulla in Normal Conditions and after Intestinal Inflammation

The nucleus raphe magnus (RMg) is a key structure of the endogenousantinociceptive system, the activity of which is regulated by serotonin5-HT1A receptors. A recipient of the RMg descending projectionsis the caudal ventrolateral medulla (cVLM)—the first supraspinalcenter for processing visceral and somatic pain signals. Intestinalpathology is known to cause persistent functional alterations inthe RMg, which are associated with the development of visceral andsomatic hyperalgesia. Presumably, a consequence of the alterationsmay be changes in the RMg modulating effects on cVLM nociceptiveactivity. However, the specific neuronal and molecular mechanismsunderlying such influence in normal conditions, as well as theirchanges in pathology remain unexplored. The aim of our neurophysiologicalexperiments performed in anesthetized adult male Wistar rats wasto compare the effects of RMg electrical stimulation on the activityof cVLM neurons evoked by visceral (colorectal distension, CRD)and somatic (tail squeezing) pain stimulations that occur in normalconditions and after intestinal inflammation (colitis), with anassessment of the contribution to these processes of the supraspinal5-HT1A receptor activation with intracerebroventricular buspirone.It has been shown that RMg can exert an inhibitory effect on bothnon-selective and differential responses of the cVLM neurons todiverse pain stimuli, causing a weakening of excitatory neuronalreactions and an increase in inhibitory responses to CRD while inhibitingboth types of reactions to tail squeezing. The RMg-evoked suppressionof nociceptive excitation in the caudal medullary neurons is enhancedunder activation of supraspinal 5-HT1A receptors by buspirone. Ithas been established that in postcolitis period the RMg inhibitoryaction on different populations of cVLM neurons are significantlydiminished, indicating an impairment of the nucleus’ antinociceptivefunction. In these conditions, the RMg descending influence losesits 5-HT1A receptor-dependent component. The changes described maycontribute to the supraspinal mechanisms underlying pathogenesisof post-inflammatory abdominal pain and comorbid somatic hyperalgesia.