REVIEW ARTICLE - THE HYPERSENSITIVE GUT - PERIPHERAL KAPPA-AGONISTS AS A NEW PHARMACOLOGICAL APPROACH

Hypersensitivity to pain is a common component of functional bowel dis orders. Hyperalgesia may be induced by various stimuli which produce a cocktail of inflammatory mediators that decrease the pain threshold. Drugs able to block these peripheral events within the gut may offer a new pharmacological approach for treating functional bowel disorders. Kappa opioids have been shown to inhibit somatic pain through a perip heral mechanism of action, acting directly on receptors located on per ipheral sensory endings. They can block both the nociceptive messages as well as the release of sensory peptides. This paper reviews the eff ects of opioid agonists on gut visceral pain and motility anomalies in duced by visceral pain. Kappa opioids have strong effects on all model s tested, with a peripheral mechanism of action allowing the design of drugs acting only in the periphery and having no central nervous syst em side-effects. This contrasts with mu agonists which are centrally a ctive on pain and worsen the subsequent transit and motility anomalies .