Background: Increasing evidence suggests that chronic stress plays an important role in the pathophysiology of several functional gastrointestinal disorders. We investigated whether CB1 and TRPV1 receptors are involved in stress induced visceral hyperalgesia.
Methods: Male rats were exposed to 1-hour water avoidance (WA) stress daily for 10 consecutive days. The visceromotor response (VMR) to colorectal distension (CRD) was measured. Immunofluorescence and Western blot analysis were used to assess the expression of CB1 and TRPV1 receptors in DRG neurons.
Results: WA stressed rats demonstrated a significant increase in the serum corticosterone levels and fecal pellet output compared to controls supporting stimulation of the HPA axis. The VMR increased significantly at pressures of 40 and 60 mmHg in WA stress rats compared with controls, respectively, and was associated with hyperalgesia. The endogenous CB1 agonist anandamide was increased significantly in DRGs from stressed rats. Immunofluorescence and Western blot analysis showed a significant decrease in CB1 and reciprocal increase in TRPV1 expression and phosphorylation in colon DRG neurons from stressed rats. These reciprocal changes in CB1 and TRPV1 were reproduced by treatment of control DRGs with anandamide in vitro. In contrast, treatment of control DRGs in vitro with the CB1 agonist WIN 55,212-2 decreased the levels of TRPV1 and TRPV1 phosphorylation. Treatment of WA stress rats in situ with WIN or the TRPV1 antagonist capsazepine prevented the development of visceral hyperalgesia and blocked the up-regulation of TRPV1.
Conclusions: These results suggest that the endocannabinoid (CB1) and TRP (TRPV1) pathways may play a potentially important role in stress-induced visceral hyperalgesia.
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