The 5-HT 4 receptor-mediated inhibition of visceral nociceptive neurons in the rat caudal ventrolateral medulla

Autor: Ivan B. Sivachenko, O. A. Lyubashina
Rok vydání: 2017
Předmět:
Zdroj: Neuroscience. 359:277-288
ISSN: 0306-4522
DOI: 10.1016/j.neuroscience.2017.07.039
Popis: Activation of the serotonin type 4 (5-HT 4 ) receptors has been reported to improve abdominal pain in patients with functional gastrointestinal disorders and reduce visceral nociception in animal models. Earlier studies have proposed that 5-HT 4 agonist can produce visceral analgesia by acting at the supraspinal level, but the underlying neuronal mechanisms remain unclear. The caudal ventrolateral medulla (CVLM) is the first site for processing of visceral nociceptive signals ascending via spinal pathways and an important component of the endogenous pain modulatory system. Therefore, the objective of the present study was to examine whether activation of 5-HT 4 receptors can affect the visceral pain-related neurons in the CVLM. In urethane-anesthetized adult male Wistar rats, we evaluated the effects of a 5-HT 4 receptor agonist, BIMU8 on ongoing firing of the CVLM neurons and their excitatory responses to noxious colorectal distension (CRD, 80 mmHg). The drug’s effect was also tested on blood pressure reactions induced by CRD–a general physiological measure of visceral nociception. Intravenous administration of BIMU8 (0.5, 1 or 2 mg/kg) produced dose-dependent suppression of both the ongoing and CRD-evoked activities of the CVLM neurons and simultaneously attenuated the depressor hemodynamic reaction to CRD. The compound’s inhibitory effect was almost completely eliminated by intracerebroventricular pretreatment with GR113808, a selective 5-HT 4 antagonist, indicating the preferential involvement of supraspinal 5-HT 4 receptors. Results indicate that visceral nociceptive transmission through the caudal medulla is negatively modulated by descending 5-HT 4 -dependent mechanisms. These findings can contribute to a deeper understanding of supraspinal processing of pain signals from the abdomen.
Databáze: OpenAIRE
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