Related Experiment Video
Updated: Jul 26, 2025
14:09
In vitro Functional Characterization of Mouse Colorectal Afferent Endings
Published on: January 21, 2015
9.6K
Evolving acidic microenvironments during colitis provide selective analgesic targets for a pH-sensitive opioid.
Claudius E Degro1,2, Nestor Nivardo Jiménez-Vargas1, Quentin Tsang1
1Gastrointestinal Diseases Research Unit, Kingston General Hospital, Queen´s University, Kingston, ON, Canada.
Pain
|June 16, 2023
Summary
A novel pH-sensitive opioid, N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP), effectively manages colitis pain throughout inflammation. NFEPP targets acidified tissues, offering analgesia without common opioid side effects.
Area of Science:
- Pharmacology
- Gastroenterology
- Pain Management
Background:
- Inflammatory conditions like colitis create an acidified microenvironment.
- pH-dependent opioids offer a novel strategy for visceral pain management with potentially fewer side effects.
- The efficacy of pH-dependent opioids during evolving inflammation and their effect on human nociceptors remain unstudied.
Purpose of the Study:
- To investigate the analgesic efficacy and side-effect profile of a pH-sensitive fentanyl analog, NFEPP, during the progression of dextran sodium sulfate-induced colitis in mice.
- To determine if NFEPP can inhibit human colonic nociceptors under acidified conditions.
- To compare the effects of NFEPP with fentanyl in the context of colitis.
Main Methods:
- Colitis was induced in mice using dextran sodium sulfate, with inflammation progression monitored.
- Visceromotor responses to colorectal distension were measured to assess nociception.
- NFEPP and fentanyl efficacy and side effects (gastrointestinal transit, defecation, hypoxemia) were evaluated.
- NFEPP's effect on mechanically provoked human colonic nociceptor activation under acidic conditions was tested.
Main Results:
- NFEPP demonstrated dose-dependent antinociceptive effects throughout colitis evolution, peaking at peak inflammation.
- Fentanyl provided analgesia irrespective of disease stage but caused significant side effects.
- NFEPP exhibited no significant gastrointestinal or respiratory side effects observed with fentanyl.
- NFEPP successfully inhibited human colonic nociceptors under simulated inflamed, acidic conditions.
Conclusions:
- NFEPP provides effective analgesia during acute colitis, with maximal efficacy during peak inflammation.
- The targeted action of NFEPP in acidified colonic tissues minimizes systemic side effects.
- NFEPP represents a promising therapeutic candidate for safe and effective pain management in conditions like ulcerative colitis flares.
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