Professor David Grundy: Research
Neurogastroenterology – The Neural control of Gut function
Our research is focused on the neural control of gut function. The term "neurogastroenterology" has been coined to describe the field of brain-gut interactions. This field has under gone rapid expansion recently for a number of reasons.
Firstly, contained within the gut wall is an enteric nervous system that is capable of autonomous activity. This enteric nervous system contains many of the transmitters and neuromodulators found in the central nervous system (CNS) and is organised into "hard-wired" circuits that control muscle and mucosal function.
These circuits contain sensory neurones, motorneurones and, like the CNS, a vast number of interneurones that enable the assimilation of information and the generation of appropriate reflex responses.
This "gut brain" is thought to allow the routine mechanisms of digestion to proceed without the involvement of the CNS, allowing the latter to concentrate on more important functions like the search for food or a sexual partner.
However, the CNS has not devolved all control to the periphery and the gut has a rich afferent innervation that sends sensory information to the brain and spinal cord and is used as a basis of reflexes through parasympathetic and sympathetic pathways that serve to co-ordinate regions of the gut that can be several metres apart and which ensure that one´s digestive needs are met.
The organisation of these interactions between local enteric mechanisms and neural controls from outside the gut wall poses questions of a fundamental nature.
Secondly, most of the sensory traffic from the gut goes unperceived but is nevertheless crucial to homeostasis. Gut afferents are also involved in nausea and vomiting, feeding and satiety and in addition generate sensations particularly under pathophysiological circumstances when the bowel can become hypersensitive.
These gut-brain communications therefore have clinical relevance to a number of gastrointestinal complaints and represent a therapeutic target for the treatment of conditions as diverse as chemotherapy-induced nausea and vomiting, inflammatory bowel disease and functional gut syndromes like the Irritable Bowel Syndrome (IBS).
Thirdly, the gastrointestinal tract must balance the ostensibly conflicting tasks of absorption and protection against potentially harmful antigenic, toxic or infectious material.
The gut performs important immune functions and a vast array of inflammatory mediators can influence the recruitment of lymphocyes and other immune cells to the gut wall, and at the same time modulate the activity of the enteric nervous system.
This coalition between immunology and enteric neurobiology, often referred to as neuroimmunophysiology, works in 2 directions. Inflammatory mediators influence the function of the local and extrinsic reflex mechanisms that regulate gut function while neural mechanisms are recognised as playing a modulatory role in the organisation of immune responses.
The latter possibly contributing to the cycles of relapse and remission in inflammatory bowel disease and IBS, relapse that is often associated with major life events; bereavement, divorce, redundancy, etc.
Finally, the enteric nervous system has the remarkable ability of being able to restore relatively normal function following pertubations in its extrinsic innervation.
A better understanding of such plasticity will be of enormous clinical implication since a failure to adapt to the ever-changing environment both from within the gastrointestinal tract and from its extrinsic innervation may underlie many disease situations.
The research group in Sheffield is internationally recognised for its work on visceral sensory mechanisms and is making in-roads into our understanding of visceral sensation mainly from a basic science standpoint.
Our experimental approaches includes immunocytochemistry, in vivo and in vitro electrophysiology, and molecular biology. We utilize knockout animals and experimental models of disease including ischaemia, inflammation and nerve injury models to provoke visceral hypersensitivity.