Establishing a novel model to study human visceral sensory signalling: P027

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Aim:The investigation of gastrointestinal sensory signalling has relied on animal models limiting translation to humans.Method:We describe a method of recording afferent discharge from resected human bowel and initial characterisation of their mechano-and chemosensitivity. Isolated segments of human colorectum were obtained from patients with bowel cancer following informed patient consent and ethical approval. 2-4cm segment distant from the tumour was pinned flat, mucosa uppermost, in a bath perfused with (34°C) physiological buffer. A mesenteric paravascular nerve bundle was attached to a suction electrode for afferent recording.Results:Successful recordings were obtained from 4/27 bowel specimens and five single units characterised. All units responded to blunt mucosalprobing, two of these showed spontaneous bursts of firing and responded to circumferential stretch but not light mucosal stroking, one responded to both stroking and stretch. 2/5 units responded to the TRPV1 agonist capsaicin (10 mM) applied to the receptive field, one of these responded to stroking. Tissue viability was confirmed histologically.Conclusions:Our data pioneer the use of human tissue for recording sensory signalling from both the mucosa and deeper layers of intestine andprovide a framework for investigating the molecular basis of human visceral sensitivity in health and disease. Funded by the BDRF.

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