Jejunal afferent nerve sensitivity in wild-type and TRPV1 knockout mice

Area of Science:

• Neuroscience
• Gastroenterology
• Physiology

Background:

• The transient receptor potential vanilloid 1 (TRPV1) receptor is implicated in sensory neurotransmission.
• Its role in mediating jejunal afferent sensitivity within the murine intestine requires further elucidation.

Purpose of the Study:

• To investigate the contribution of the TRPV1 receptor to jejunal afferent sensitivity in the murine intestine.
• To determine the specific mechanisms by which TRPV1 influences gut mechanosensation and chemosensation.

Main Methods:

• In vitro multiunit activity recording from mesenteric afferents of wild-type (WT) and TRPV1 knockout (TRPV1(-/-)) mice.
• Stimulation via gut distension (0-60 mmHg), intraluminal hydrochloric acid (20 mM), and bradykinin (1 µM).
• Administration of TRPV1 antagonist capsazepine and agonist capsaicin.

Main Results:

• TRPV1(-/-) mice exhibited significantly lower afferent responses to distension compared to WT mice.
• Wide dynamic range afferent fibers showed a downward shift in pressure-response curves in TRPV1(-/-) mice.
• Responses to intraluminal acid were attenuated in TRPV1(-/-) mice, while bradykinin responses were unaffected.
• Capsazepine attenuated responses to distension, acid, and bradykinin in WT mice.
• WT jejunal afferents responded to capsaicin, but TRPV1(-/-) afferents did not.

Conclusions:

• TRPV1 activation sensitizes small intestinal afferent neurons, playing a key role in jejunal afferent signaling.
• TRPV1 is crucial for mediating responses to mechanical distension and chemical stimuli like acid.
• TRPV1 does not appear to mediate responses to bradykinin in this context.