Lyubashina Olga A, Sushkevich Boris M, Sivachenko Ivan B
Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences, Saint Petersburg, Russia.
Eur J Neurosci. 2025 Jan;61(2):e16677. doi: 10.1111/ejn.16677.
The serotonergic raphe magnus (RMg) and dorsal raphe (DR) nuclei are crucial pain-regulating structures, which nociceptive activity is shown to be altered in gut pathology, but the underlying neuroplastic changes remain unclear. Considering the importance of 5-HT1A receptors in modulating both pain and raphe neuronal activity, in this study, we aimed to determine whether 5-HT1A-dependent visceral and somatic nociceptive processing within the RMg and DR is modified in postcolitis conditions. In anaesthetised male Wistar rats, healthy control and recovered from TNBS-induced colitis, the microelectrode recordings of RMg and DR neuron responses to noxious colorectal distension (CRD) or tail squeezing (TS) were performed prior and after intravenous administration of 5-HT1A agonist, buspirone. In postcolitis animals, 5-HT1A autoreceptor- and heteroreceptor-activating high doses of buspirone (2 and 4 mg/kg) lost normally occurring ability to facilitate CRD- and TS-evoked activation of RMg neurons, causing inhibition of the local nociceptive signalling similar to 5-HT1A autoreceptor-activating low doses (0.1 and 0.5 mg/kg). Conversely, the normally inherent property of buspirone at all doses to reduce visceral and somatic pain-related neuronal excitation in the DR was weakened after colitis. These phenomena were associated with a loss of normally occurring inhibitory effect of the compound's high doses on hemodynamic reactions to CRD and TS, revealing deficient antinociceptive action at a systemic level. The data suggest postcolitis changes in buspirone-dependent 5-HT1A autoreceptor- and heteroreceptor-mediated signalling, which can directly or indirectly lead to reduced RMg pain-related activity and increased DR nociceptive excitation, impairing their functioning in the visceral and somatic pain control.
血清素能中缝大核（RMg）和中缝背核（DR）是关键的疼痛调节结构，在肠道病理状态下其伤害性感受活动会发生改变，但潜在的神经可塑性变化仍不清楚。鉴于5-HT1A受体在调节疼痛和中缝神经元活动方面的重要性，在本研究中，我们旨在确定在结肠炎后状态下，RMg和DR内依赖5-HT1A的内脏和躯体伤害性感受处理是否发生改变。在麻醉的雄性Wistar大鼠中，分为健康对照组和从三硝基苯磺酸（TNBS）诱导的结肠炎中恢复的大鼠，在静脉注射5-HT1A激动剂丁螺环酮之前和之后，对RMg和DR神经元对有害结肠扩张（CRD）或尾部挤压（TS）的反应进行微电极记录。在结肠炎后动物中，5-HT1A自身受体和异受体激活的高剂量丁螺环酮（2和4mg/kg）失去了正常促进CRD和TS诱发的RMg神经元激活的能力，导致局部伤害性信号传导受到抑制，类似于5-HT1A自身受体激活的低剂量（0.1和0.5mg/kg）。相反，丁螺环酮在所有剂量下正常具有的减轻DR中内脏和躯体疼痛相关神经元兴奋的特性在结肠炎后减弱。这些现象与该化合物高剂量对CRD和TS血流动力学反应的正常抑制作用丧失有关，揭示了全身水平上抗伤害感受作用的不足。数据表明结肠炎后丁螺环酮依赖的5-HT1A自身受体和异受体介导的信号传导发生改变，这可能直接或间接导致RMg疼痛相关活动减少和DR伤害性兴奋增加，损害它们在内脏和躯体疼痛控制中的功能。
