Mu and delta opioid receptor knockout mice show increased colonic sensitivity

Area of Science:

• Neuroscience
• Gastroenterology
• Pharmacology

Background:

• Opiates modulate pain via opioid receptors.
• Investigated endogenous mu (MOR) and delta (DOR) opioid receptor activity in colonic pain control.

Purpose of the Study:

• To determine if global or peripheral MOR and DOR activity influences visceral sensitivity.
• To assess the role of endogenous opioid tone in visceral pain and colitis.

Main Methods:

• Compared global MOR/DOR knockout mice, conditional knockout mice (Nav1.8 neurons), and controls.
• Assessed visceromotor responses to colorectal distension (CRD) in naïve and colitis models.
• Measured opioid gene and cytokine expression via quantitative RT-PCR.

Main Results:

• Global MOR/DOR knockout mice exhibited increased visceral sensitivity, unlike conditional knockouts.
• MOR and preproenkephalin were highly expressed in the colon.
• Colitis induced comparable hypersensitivity across mouse lines, indicating insufficient endogenous analgesia.

Conclusions:

• Global MOR and DOR activity, not peripheral activity, affects visceral sensitivity in naïve mice.
• Endogenous MOR and DOR tones are insufficient for analgesia in DSS-induced colitis.
• Endogenous mu and delta opioid analgesia presents potential therapeutic targets for chronic intestinal pain.