New Oral Peptide Therapy Targets Chronic Abdominal Pain Without Opioid Risks

Chronic abdominal pain, a debilitating symptom of conditions like irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD), has long relied on opioids for relief—despite their severe side effects and addiction risks. A team at the University of Vienna, led by medicinal chemist Markus Muttenthaler, has introduced a groundbreaking alternative: a class of oral peptide therapeutics that specifically target oxytocin receptors in the gut. Published in Angewandte Chemie, this innovation could transform the management of chronic abdominal pain by offering a safe, non-opioid option.

A Gut-Specific Solution to an Ongoing Problem

Current treatments for abdominal pain often involve opioids, which come with significant drawbacks, including addiction, sedation, nausea, and constipation. By affecting the central nervous system, opioids compromise patients’ quality of life and contribute to the global opioid crisis. The new therapeutic approach developed by Muttenthaler’s team sidesteps these issues by targeting oxytocin receptors localized in the gut.

While oxytocin—the “love hormone”—is better known for its role in social bonding, it also plays a role in modulating pain. By stimulating gut-specific oxytocin receptors, the new peptides effectively reduce pain signals without systemic side effects. The researchers overcame a significant hurdle: oxytocin is typically degraded in the gastrointestinal tract and cannot be administered orally. Through advanced medicinal chemistry, the team developed gut-stable, orally available oxytocin analogs that retain their potency and selectivity.

Why This Matters

This innovation has the potential to radically improve care for patients with chronic abdominal pain. Unlike opioids, which act systemically and carry significant risks, this gut-restricted therapy offers a localized solution with a reduced side effect profile. Additionally, its oral formulation represents a significant step forward compared to most peptide drugs, such as insulin and GLP-1 analogs, which require injection.

Muttenthaler noted that their research highlights “the therapeutic potential of gut-specific peptides and offers a new, safe alternative to existing pain medications, particularly for those suffering from chronic gut disorders and abdominal pain.” This approach not only addresses an unmet need in chronic pain management but also opens new avenues for peptide therapeutics in gastrointestinal diseases.

Future Implications

The research team has already patented the drug leads and is working to bring these peptides to market, with support from the European Research Council. They are now seeking industrial partners and investors to accelerate clinical development. If successful, this innovation could revolutionize the treatment landscape for gastrointestinal disorders by establishing oral, gut-specific peptide drugs as a new therapeutic paradigm.

With its focus on gut-stable peptides, this approach could expand beyond pain management to address other gastrointestinal conditions, opening the door to a new era of peptide-based treatments.