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Visceral pain is the most common form of pain produced by disease and is thus of interest in the study of gastrointestinal (GI) complaints such as irritable bowel syndrome, in which sensory signals perceived as GI pain travel in extrinsic afferent neurones with cell bodies in the dorsal root ganglia (DRG). The DRG from which the primary spinal afferent(More)
The gastrointestinal tract contains most of the body's 5-hydroxytryptamine (5-HT) and releases large amounts after meals or exposure to toxins. Increased 5-HT release occurs in patients with irritable bowel syndrome (IBS) and their peak plasma 5-HT levels correlate with pain episodes. 5-HT(3) receptor antagonists reduce symptoms of IBS clinically, but their(More)
The aim of this study was to investigate the contribution of the TRPV1 receptor to jejunal afferent sensitivity in the murine intestine. Multiunit activity was recorded in vitro from mesenteric afferents supplying segments of mouse jejunum taken from wild-type (WT) and TRPV1 knockout (TRPV1(-/-)) animals. In WT preparations, ramp distension of the gut (up(More)
Lumbar splanchnic (LSN) and sacral pelvic (PN) nerves convey different mechanosensory information from the colon to the spinal cord. Here we determined whether these pathways also differ in their chemosensitivity and receptor expression. Using an in vitro mouse colon preparation, individual primary afferents were tested with selective P2X and transient(More)
1. Recordings of the activity of the large conductance Ca2+-activated K+ (BK) channel from over 90 % of inside-out patches excised from acutely dissociated hippocampal CA1 neurones revealed an inactivation process dependent upon the presence of at least 1 microM intracellular Ca2+. Inactivation was characterized by a sudden switch from sustained high open(More)
Irritable bowel syndrome (IBS) is a multifactorial condition with principal symptoms of pain and altered bowel function. The kappa-opioid agonist asimadoline is being evaluated in Phase III as a potential treatment for IBS. Asimadoline, to date, has shown a good safety profile and the target Phase III population - diarrhea-predominant IBS patients with at(More)
Despite its beneficial effect in IBS patients, the mechanism of action of the 5-HT3 receptor (5-HT3R) antagonist alosetron is still incompletely understood. We aimed to characterize the effect and site(s) of action in a model of stress-induced sensitization of visceral nociception in rats. Adult male Wistar rats were equipped for recording of visceromotor(More)
Opioid receptors in the gastrointestinal (GI) tract mediate the effects of endogenous opioid peptides and exogenously administered opioid analgesics, on a variety of physiological functions associated with motility, secretion and visceral pain. The studies reviewed or reported here describe a range of in vivo activities of opioid receptor antagonists upon(More)
BACKGROUND & AIMS Octreotide inhibits visceral sensations in clinical studies, but the site of action and the receptor type(s) involved are unknown. Our aim was to investigate the effects of octreotide, the selective sst(2) receptor agonist (BIM 23027), and the sst(2) antagonist (Cyanamid154806) on the activity of mesenteric afferent fibers innervating the(More)
The presence of 5-hydroxytryptamine(3) receptors on enteric neurons is known from pharmacological data that date back more than 40 years. However, an adequate account of which neurons bear these receptors has not been made because suitable antisera have not been available. We have found that the majority of antisera that have been raised against sequences(More)