Extrinsic primary afferent signalling in the gut

Abstract

Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors, and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that there are just five structurally distinct types of sensory endings in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators.Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.2

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

“…[57] There are a number of different types of afferent spinal nerve endings that innervate the gastrointestinal tract, where they may detect the release of neuroactive compounds. [67] Signals from these neurons may then reach the amygdala via the brainstem (spinoparabrachial pathway) and the thalamus (spinothalamic pathway). [68] Importantly, it is now known that the gut microbiota can directly produce many neurotransmitters used for communication in the ENS and CNS (e.g., gammaaminobutyric acid [GABA], norepinephrine, dopamine, acetylcholine, serotonin) and stimulate the production of others.…”

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

“…These afferent nerves respond linearly to increasing levels of distension and signal into the noxious range. They also express putative nociceptive channels, including members of the Transient Receptor Potential (TRPV1, TRPA1) and Acid Sensing Ion Channel 6 (ASIC3) families, implying they act as intensity encoders and modulate the sensory processing of pain (Brierley et al, 2009;Brookes et al, 2013;Gebhart, 2000;Jones et al, 2005). Immune derived mediators are known to excite viscerosensory nerves and have previously been implicated in the heightened sensitivity to distension of the colo-rectum experienced by IBS patients (Hughes et al, 2009a;Hughes et al, 2013b).…”

Effects of Inflammation on the Innervation of the Colon

“…The remaining spinal afferent neurons convey information to the CNS on the contractile and chemical state of GI organs. The nerve terminals of spinal afferent neurons are located in the muscle layers, the mucosa, and along blood vessels (Brookes et al 2013). The mucosal endings can be excited by the release of enteroendocrine substances, such as serotonin released in response to luminal stimuli, or by direct mechanical stimulation.…”

“…There are 2 populations of extrinsic afferent neurons that innervate the GI tract: those that synapse in the brain stem and those that synapse in the spinal cord (Brookes et al 2013;Furness 2012). The axons of the neurons that synapse in the brain stem are contained in the vagus nerve; thus the neurons are called vagal afferent neurons.…”