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

Pub Date : 2024-08-29 DOI:10.1134/s002209302404015x

B. M. Sushkevich, I. B. Sivachenko, O. A. Lyubashina

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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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在正常情况下和肠道炎症后刺激大鼠腹侧文丘里核对痛觉神经元的影响

摘要大剑突核（RMg）是内源性痛觉系统的一个关键结构，其活动受5-羟色胺5-HT1A受体的调节。尾部腹外侧髓质（cVLM）是RMg降序投射的受体，也是处理内脏和躯体疼痛信号的第一个棘上中心。众所周知，肠道病变会引起 RMg 的持续功能性改变，这与内脏和躯体痛觉减退的发生有关。据推测，这种改变的后果可能是 RMg 对 cVLM 痛觉活动的调节作用发生了变化。然而，这种影响在正常情况下的具体神经元和分子机制，以及它们在病理情况下的变化仍有待探索。我们在麻醉的成年雄性 Wistar 大鼠身上进行神经生理学实验的目的是比较 RMg 电刺激对内脏（结肠直肠胀气）和躯体（尾部胀气）诱发的 cVLM 神经元活动的影响、同时评估脑室内丁螺环酮激活脊髓上 5-HT1A 受体对这些过程的贡献。研究表明，RMg 可对 cVLM 神经元对不同疼痛刺激的非选择性和差异性反应产生抑制作用，导致神经元对 CRD 的兴奋性反应减弱和抑制性反应增强，同时抑制对尾部挤压的两种反应。在丁螺环酮激活脊髓上5-HT1A受体的情况下，RMg诱发的尾髓神经元痛觉兴奋抑制作用增强。已经证实，在结肠炎后时期，RMg 对 cVLM 不同神经元群的抑制作用显著减弱，表明该神经核的抗痛觉功能受损。在这些情况下，RMg 下降影响失去了 5-HT1A 受体依赖成分。所述变化可能与炎症后腹痛和合并躯体痛觉减退的超脊髓发病机制有关。

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