Effects of the Nucleus Raphe Magnus Stimulation on Nociceptive Neurons of the Rat Caudal Ventrolateral Medulla in Normal Conditions and after Intestinal Inflammation
B. M. Sushkevich, I. B. Sivachenko, O. A. Lyubashina
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引用次数: 0
Abstract
The nucleus raphe magnus (RMg) is a key structure of the endogenous
antinociceptive system, the activity of which is regulated by serotonin
5-HT1A receptors. A recipient of the RMg descending projections
is the caudal ventrolateral medulla (cVLM)—the first supraspinal
center for processing visceral and somatic pain signals. Intestinal
pathology is known to cause persistent functional alterations in
the RMg, which are associated with the development of visceral and
somatic hyperalgesia. Presumably, a consequence of the alterations
may be changes in the RMg modulating effects on cVLM nociceptive
activity. However, the specific neuronal and molecular mechanisms
underlying such influence in normal conditions, as well as their
changes in pathology remain unexplored. The aim of our neurophysiological
experiments performed in anesthetized adult male Wistar rats was
to compare the effects of RMg electrical stimulation on the activity
of cVLM neurons evoked by visceral (colorectal distension, CRD)
and somatic (tail squeezing) pain stimulations that occur in normal
conditions and after intestinal inflammation (colitis), with an
assessment of the contribution to these processes of the supraspinal
5-HT1A receptor activation with intracerebroventricular buspirone.
It has been shown that RMg can exert an inhibitory effect on both
non-selective and differential responses of the cVLM neurons to
diverse pain stimuli, causing a weakening of excitatory neuronal
reactions and an increase in inhibitory responses to CRD while inhibiting
both types of reactions to tail squeezing. The RMg-evoked suppression
of nociceptive excitation in the caudal medullary neurons is enhanced
under activation of supraspinal 5-HT1A receptors by buspirone. It
has been established that in postcolitis period the RMg inhibitory
action on different populations of cVLM neurons are significantly
diminished, indicating an impairment of the nucleus’ antinociceptive
function. In these conditions, the RMg descending influence loses
its 5-HT1A receptor-dependent component. The changes described may
contribute to the supraspinal mechanisms underlying pathogenesis
of post-inflammatory abdominal pain and comorbid somatic hyperalgesia.
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