I. Receptors on visceral afferents

Abstract

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 enhance 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.

Neuroanatomy of visceral nociception: vagal and splanchnic afferent

“…Bradykinin and prostaglandins interact in a potentiating way to modulate the sensitivity of spinal afferent endings, reducing the threshold for activation to cause hypersensitivity. 12 Previously insensitive afferents have also been shown to develop mechanosensitivity during inflammation. A wide range of chemical mediators are implicated in this sensitisation process.…”

Adrenergic β2-Receptors Mediates Visceral Hypersensitivity Induced by Heterotypic Intermittent Stress in Rats

“…Both the central sensitization and peripheral sensitization have been implicated in the development of visceral hypersensitivity [17], [18]. The peripheral sensitization involves an enhanced excitability of primary afferent nociceptors, which are the information superhighway from the gut to the spinal cord and convey peripheral stimuli into action potentials that propagate to the central nervous system [17]. Sensitization of primary sensory afferents is maintained by a number of membrane receptors and ion channels.…”

Altered expression of P2X3 in vagal and spinal afferents following esophagitis in rats

“…The excitability of primary sensory neuron innervating the gastrointestinal (GI) tract is enhanced following injury, ischemia, and visceral inflammation (Cooke et al 2003; Holzer 2001; Kirkup et al 2001). In recent years, purinergic neurotransmitter adenosine tri-phosphate (ATP) has been widely recognized as a fast synaptic neurotransmitter in both peripheral and central neurons and activation of various purinergic receptors is reported to play an important role in nociceptive signaling (Bardoni et al 1997; Evans 1996; Khakh et al 1995; Sawynok and Reid 1997).…”