Cover Image

Abstract

The cover image, by K.‐S. Ng et al., is based on the Original Article Quantification and neurochemical coding of the myenteric plexus in humans: No regional variation between the distal colon and rectum, DOI: .

Human visceral nociception: findings from translational studies in human tissue

“…One alternative method we, and others, have employed to address the challenge of conducting translational studies on visceral pain is to utilise macroscopically normal tissue obtained following pathological inspection from the margins of surgically resected human bowel (42, 51,54,56,80). This is obtained from consenting patients undergoing surgery as part of their clinical treatment for GI diseases, most commonly bowel cancer.…”

“…This is obtained from consenting patients undergoing surgery as part of their clinical treatment for GI diseases, most commonly bowel cancer. Using suction and wire electrode approaches, neuronal activity can be recorded from mesenteric nerves innervating ileum, colon or rectum and receptive fields identified and studied in flat-sheet preparations (54,56). Alternatively, mesenteric nerve activity can be recorded from the human appendix when cannulated as a tubular preparation, which enables luminal distension in a manner comparable to similar approaches in rodent tissue (36).…”

“…Specifically, the nerve endings studied are stimuli, no significant difference was observed between those stored overnight at 4C compared to those used straight from surgery (51). Importantly, all groups report immediate extraction from surgery into pre-oxygenated Krebs buffer for transport to laboratories and gross dissection (42, 51,54,56,80). Whilst the effects of cessation of blood supply on the tissues cannot be directly evaluated,…”

“…Vascular afferents, unlike muscular or mucosal subtypes, have activation thresholds to mechanical distension (>40 mmHg) that are painful in humans, and they are also activated by algogenic chemical mediators such as capsaicin, bradykinin, and ATP. A recent study by our group using single-cell RNA sequencing of colonic sensory neurones has identified molecular markers for 7 molecularly distinct subtypes, further facilitating the investigation of those fibres responsible for transducing noxious stimuli (38).By understanding which sensory afferents are responsible for transducing pain, we can not only focus drug discovery efforts on mechanisms capable of modulating the neuronal sensitivity in these afferents, but also focus basic research specifically on how these afferents change in disease.Studies of human bowel afferents have identified, in addition to spontaneous activity, receptive fields responsive to von Frey hair probe(54,56), light mucosal stroke (42) and circumferential stretch (42, 80) suggesting that a comparable repertoire of afferent subtypes to those found in rodents is also present in humans(Fig. 1).…”