A selective, high affinity 5-HT_2Breceptor antagonist inhibits visceral hypersensitivity in rats

Abstract

These results suggest that 5-HT(2B)receptors are involved in signaling from the colon in rats in which there is visceral hypersensitivity and that a selective 5-HT(2B)receptor antagonist could have therapeutic potential for the treatment of gut disorders characterized by visceral hypersensitivity.

Antinociceptive effect of peripheral serotonin 5-HT2B receptor activation on neuropathic pain

“…In conclusion, our study shows for the first time that peripheral 5-HT 2B R activation can both prevent and cure CCI-induced neuropathic pain, whereas previous studies have reported opposite findings in other pain models, such as migraine [29,50,51] and visceral pain [45,47]. In these cases, the etiology of pain is quite different from that of neuropathic pain.…”

Activation of Colonic Mucosal 5-HT4 Receptors Accelerates Propulsive Motility and Inhibits Visceral Hypersensitivity

“…34,35 5-HT 2B R antagonists suppress VMR responses in Wistar Kyoto rats 35 and in a model of trinitrobenzene sulfonic acid (TNBS)–induced colonic hypersensitivity. 36 Also, tegaserod is an antagonist at the 5-HT 2B R, in addition to its more potent action as a 5-HT 4 R agonist. 37 However, previous studies of rats with acetic acid–induced colonic hypersensitivity showed that the tegaserod-induced attenuation of VMR was partially inhibited by 5-HT 4 R antagonism, but no additional inhibition of the antinociceptive response was observed after co-administration of a 5-HT 2B R antagonist.…”

Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey

“…Milnacipran, a dual 5-HT/NA uptake inhibitor (1-30mg/kg/i.p), reversed repeated forced-swim stress-induced muscle hyperalgesia (Suarez-Roca et al, 2006a) suggesting the same effect. Similarly, in WKY rats, intracerebroventricular administration of a 5-HT2B antagonist reduced pain behaviours during colorectal distension (O'Mahony et al, 2010) and 5-HT2B receptors mediate restraint stress-induced visceral hypersensitivity in mice (Ohashi-Doi et al, 2010). Treatments using drugs regulating monoamines in hyperalgesia and negative effect are very well established but the underlying mechanism is yet to be determined.…”