Visceral perception: inflammatory and non-inflammatory mediators

Abstract

Visceral hypersensitivity is currently the most widely accepted mechanism responsible for abdominal pain. Inflammatory mediators are known to sensitise primary afferents and to recruit silent nociceptors. Recent evidence suggests that non-inflammatory mediators also have the potential to trigger visceral pain. This sequence of events may constitute part of an alerting system which prompts the central nervous system to correct gastrointestinal responses to ingestion.

Figure 1

Substances and major local pathways involved in triggering hyperalgesia to distension within the gut. Note that several mediators such as substance P (SP) may directly and indirectly influence the threshold of response of afferent fibres to a mechanical stimulus. CGRP, calcitonin gene related peptide; C5a, complement 5a; fMLP, formyl-methionyl-leucyl-phenylanine; IL, interleukin; NGF, nerve growth factor; NPY, neuropeptide Y; PGI₂, prostacyclin I₂; PGE ₂, prostaglandin E₂; TNF, tumour necrosis factor; VIP, vasoactive intestinal peptide; 5-HT, serotonin; 8(R),15(S)-diHETE, 8(R),15(S)-dihydroxyeicosatetraenoic acid. Modified from Coelho and colleagues.³⁴

Figure 2

Pathways, structures, and mediators involved in stress induced hyperalgesia to visceral (rectal) mechanical stimulus. ANS, autonomic nervous system; CRF, corticotrophin releasing factor; DRG, dorsal root ganglia; NKA, neurokinin A; SP, substance P; 5-HT, serotonin.