Neuroanatomy of visceral nociception: vagal and splanchnic afferent

Abstract

Afferent fibres convey sensory information from the upper gastrointestinal tract to the central nervous system but the nature of this information is different for vagal and spinal pathways. Vagal afferents convey predominantly physiological information while spinal afferents are able to encode noxious events. Because of the different response profiles following activation of these pathways, it is likely that vagal and splanchnic afferents play different roles in mediating sensation.

Figure 1

Arrangement of the primary afferent neurones within the intestine. DRG, dorsal root ganglion. Reproduced with permission from Furness and colleagues.¹

Figure 2

Potential receptor mechanisms underlying activation (depolarisation) and sensitisation of visceral sensory afferents. Some mediators, for example, serotonin (5-HT) acting on 5-HT₃ receptors, cause activation while some (prostaglandin E₂ (PGE₂)) cause sensitisation. Others, for example adenosine, cause both stimulation and sensitisation. Bradykinin has a self sensitising action, stimulating discharge through activation of phospholipases (PLs) and enhancing excitability via PGs. Inflammatory mediators can be released from a variety of cell types (for example, sympathetic varicosities, mast cells, and blood vessels) present in or around the afferent nerve terminal. 5-HT, adenosine triphosphate (ATP), and capsaicin can directly activate non-selective cation channels (NSCCs) while adenosine, histamine, PGs (not PGE₂), and proteases such as tryptase and thrombin act on G protein coupled receptors leading to a Ca²⁺ dependent modulation of ion channel activity. Sensitisation may be mediated via cyclic adenosine 3,5-monophosphate (cAMP). Adenosine and PGE₂ can generate cAMP directly through G protein coupled stimulation of adenyl cyclase (AC). In contrast, histamine may act indirectly through generation of PGs. The actions of cAMP downstream are currently unknown but may involve modulation of ion channels, interaction with other second messengers, such as Ca²⁺, or even changes in receptor expression. COX, cyclooxygenase; DAG, diacylglycerol; IP₃, inositol 1,4,5-triphosphate; PARs, protease activated receptors; PLC, phospholipase C; PLA₂, phospholipase A₂; PKC, protein kinase C. Modified from Kirkup and colleagues.¹²