The transient receptor potential vanilloid 1 receptor (TRPV1) is an important nociceptor involved in
neurogenic inflammation. We aimed to examine the role of TRPV1 in experimental
colitis and in the development of visceral
hypersensitivity to mechanical and chemical stimulation. Male Sprague-Dawley rats received a single dose of
trinitrobenzenesulfonic acid (TNBS) in the distal colon. In the preemptive group, rats received the
TRPV1 receptor antagonist
JYL1421 (10 mumol/kg, i.v.) or vehicle 15 min prior to TNBS followed by daily doses for 7 days. In the post-
inflammation group, rats received
JYL1421 daily for 7 days starting on day 7 following TNBS. The visceromotor response (VMR) to colorectal distension (CRD), intraluminal
capsaicin,
capsaicin vehicle (pH 6.7) or acidic saline (pH 5.0) was assessed in all groups and compared with controls and naïve rats. Colon
inflammation was evaluated with H&E staining and
myeloperoxidase (MPO) activity. TRPV1 immunoreactivity was assessed in the thoraco-lumbar (TL) and lumbo-sacral (LS) dorsal root ganglia (DRG) neurons. In the preemptive vehicle group, TNBS resulted in a significant increase in the VMR to CRD, intraluminal
capsaicin and acidic saline compared the JYL1421-treated group (P<0.05). Absence of
microscopic colitis and significantly reduced MPO activity was also evident compared with vehicle-treated rats (P<0.05). TRPV1 immunoreactivity in the TL (69.1+/-4.6%) and LS (66.4+/-4.2%) DRG in vehicle-treated rats was increased following TNBS but significantly lower in the preemptive JYL1421-treated group (28.6+/-3.9 and 32.3+/-2.3 respectively, P<0.05).
JYL1421 in the post-
inflammation group improved
microscopic colitis and significantly decreased the VMR to CRD compared with vehicle (P<0.05, >/=30 mm Hg) but had no effect on the VMR to chemical stimulation. TRPV1 immunoreactivity in the TL and LS DRG was no different from vehicle or naïve controls. These results suggest an important role for TRPV1 channel in the development of
inflammation and subsequent mechanical and chemical visceral
hyperalgesia.