Are there any agents being developed specifically for visceral pain?
Linaclotide, a guanylate cyclase inhibitor, and lubiprostone, a chloride channel activator, have demonstrated analgesic efficacy in both animal models of visceral pain and patients with constipation-predominant irritable bowel syndrome. In humans, the analgesic efficacy of these drugs is closely tied to their promotility effects. Serotonin receptor subtype 3 (5HT3R) antagonists, like alosetron, have similar visceral analgesic effects; however, severe restrictions have been placed on its use due to adverse effects of ischemic colitis. Eluxadoline, a mixed agonist/antagonist at mu-, delta-, and kappa-opioid receptors, has recently been demonstrated to be effective for both pain and diarrhea in patients with IBS diarrhea-predominant subtypes. P2X purinoreceptor 3 antagonists are undergoing animal studies. The P2X3 receptor functions as a ligand-gated ion channel that may transduce ATP-evoked nociceptor activation, thought to be involved in visceral pain mediation. Antagonism results in pain relief in mouse models of visceral pain.
