Visceral pain is both different and similar to somatic pain - different in being poorly localized and usuallyreferred elsewhere to the body wall, but similar in many of the molecular mechanisms it employs (like TRP channels) andthe specialization of afferent endings to detect painful stimuli. TRPV1 is sensitive to low pH. pH is lowest in gastric juice,which may cause severe pain when exposed to the oesophageal mucosa, and probably works via TRPV1. TRPV1 is foundin afferent fibres throughout the viscera, and the TRPV1 agonist capsaicin can recapitulate symptoms experienced indisease. TRPV1 is also involved in normal mechanosensory function in the gut. Roles for TRPV4 and TRPA1 have alsobeen described in visceral afferents, and TRPV4 is highly enriched in them, where it plays a major role in bothmechanonociception and chemonociception. It may provide a visceral-specific nociceptor target for drug development.TRPA1 is also involved in mechano-and chemosensory function, but not as selectively as TRPV4. TRPA1 is colocalizedwith TRPV1 in visceral afferents, where they influence each other's function. Another modulator of TRPV1 is thecool/mint receptor TRPM8, which, when activated can abrogate responses mediated via TRPV1, suggesting that TRPM8agonists may provide analgesia via this pathway. In all, the viscera are rich in TRP channel targets on nociceptiveneurones which we hope will provide opportunities for therapeutic analgesia.
展开▼
