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Papers: 24 Feb 2024 - 1 Mar 2024

2024 Feb 27



Intracerebroventricular Administration of TRH Agonist, RX-77368 Alleviates Visceral Pain Induced by Colorectal Distension in Rats.


Larauche M, Kim YS, Mulak A, Duboc H, Taché Y


Thyrotropin-releasing hormone (TRH) acts centrally to exert pleiotropic actions independently from its endocrine function, including antinociceptive effects against somatic pain in rodents. Whether exogenous or endogenous activation of TRH signaling in the brain modulates visceral pain is unknown. Adult male Sprague-Dawley rats received an intracerebroventricular (ICV) injection of the stable TRH analog, RX-77368 (10, 30 and 100ng/rat) or saline (5µl) or were semi-restrained and exposed to cold (4°C) for 45min. The visceromotor response (VMR) to graded phasic colorectal distensions (CRD) was monitored using non-invasive intracolonic pressure manometry. Naloxone (1mg/kg) was injected subcutaneously 10min before ICV RX-77368 or saline. Fecal pellet output was monitored for 1h after ICV injection. RX-77368 ICV (10, 30 and 100ng) reduced significantly the VMR by 56.7%, 67.1% and 81.1% at 40mmHg and by 30.3%, 58.9% and 87.4% at 60mmHg respectively vs ICV saline. Naloxone reduced RX-77368 (30 and 100ng, ICV) analgesic response by 51% and 28% at 40mmHg and by 30% and 33% at 60mmHg respectively, but had no effect per se. The visceral analgesia was mimicked by the acute exposure to cold. At the doses of 30 and 100ng, ICV RX-77368 induced defecation within 30min. These data established the antinociceptive action of RX-77368 injected ICV in a model of visceral pain induced by colonic distension through recruitment of both opioid and non-opioid dependent mechanisms.