I. Receptors on visceral afferents

Anthony J. Kirkup, Alan M. Brunsden, David Grundy
2001 American Journal of Physiology - Gastrointestinal and Liver Physiology  
Kirkup, Anthony J., Alan M. Brunsden, and David Grundy. Receptors and Transmission in the Brain-Gut Axis: Potential for Novel Therapies. I. Receptors on visceral afferents. Am J Physiol Gastrointest Liver Physiol 280: G787-G794, 2001.-Visceral afferents are the information superhighway from the gut to the central nervous system. These sensory nerves express a wide range of membrane receptors that can modulate their sensitivity. In this themes article, we concentrate on those receptors that
more » ... ce the excitability of visceral afferent neurons. Some receptors are part of a modality-specific transduction pathway involved in sensory signaling. Others, which are activated by substances derived from multiple cellular sources during ischemia, injury, or inflammation, act in a synergistic fashion to cause acute or chronic sensitization of the afferent nerves to mechanical and chemical stimuli. Such hypersensitivity is the hallmark of conditions such as irritable bowel syndrome. Accordingly, these receptors represent a rational target for drug treatments aimed at attenuating both the inappropriate visceral sensation and the aberrant reflex activity that are the foundation for alterations in bowel function. spinal afferents; sensitization THERE ARE TWO REASONS WHY receptors on the peripheral processes of afferent neurons are a rational target for treating conditions of visceral hyperalgesia like irritable bowel syndrome (IBS). First, these afferent nerve terminals initiate the sensory signals that are transmitted from the gut to the brain and ultimately bring about the perception of visceral events including nausea, satiety, and pain. Second, these same visceral afferents, through local and central reflexes, modulate gastrointestinal motor and secretory activity that ensures that the digestive needs of the individual are met and that, under certain circumstances, may be disturbed, leading to diarrhea or constipation. Therefore, the "Holy Grail" is a single therapeutic target with the potential to attenuate both visceral sensation and aberrant reflex activity and so restore motility and secretion to normal. The properties of visceral afferents have been dealt with extensively in recent themes articles, and we do not propose to cover this ground. Instead, we focus on the excitatory receptors expressed on the afferent terminals in the gut wall and consider the role these receptors play in visceral sensation and how this may relate to the development of novel therapies. In this context, we exclusively consider the receptor mechanisms present in extrinsic afferent nerves of the gastrointestinal tract, which send processes to the central nervous system. The activation pathways of primary afferent neurons or intestinofugal fibers that are a component of the enteric nervous system are not covered because, although they may modulate conscious sensation indirectly through changing the environment around extrinsic afferent nerves, they do not themselves impinge on consciousness directly. The mechanisms involved in visceral perception are generally less well understood than their corresponding sensations in the somatic realm, but there are a number of common features. Similar types of nerve, e.g., small-diameter unmyelinated (C) or thinly myelinated (A␦) fibers convey both visceral and somatic painful sensations. However, visceral pain is poorly localized and is often referred to somatic sites because their inputs converge in the dorsal horn of the spinal cord. In addition, the thoracic and abdominal viscera project sensory information to the brain stem via vagal afferent pathways. From what we describe below, the available evidence indicates that these two classes of visceral extrinsic nerves (vagal and spinal) exhibit a number of contrasting properties, which in turn reflect their diverse roles in sensory signaling. RECEPTORS ON SENSORY NEURONS An enormous range of chemical mediators have been implicated in sensory signal transduction in the vis-
doi:10.1152/ajpgi.2001.280.5.g787 pmid:11292585 fatcat:vvk7mlxbk5efbkju4qio74idnm