The receptor, which is tied in with calcium metabolism pathways, turns out to have an active role in two very important areas. It appears to play a central role in initiating inflammatory responses AND integrating painful stimuli.

Afferent impulses involved in signaling from normal bladder are transmitted by myelinated A? fibers which respond to distention and bladder filling, whereas noxious stimuli are transmitted by unmyelinated C-fibers. TRPV1 is expressed predominantly by primary sensory neurons involved in nociception and neurogenic inflammation. These neurons can be activated and desensitized by vanilloids, a group of chemicals which include the neurotoxin capsaicin and related compounds such as resiniferatoxin. Liu and colleagues from Sydney, Australia studied possible changes in TRPV1 mRNA expression in different regions of the bladder from female patients with sensory urgency (SU) and compared the findings with those of female patients with idiopathic detrusor overactivity (DO) and asymptomatic women. The hypothesis was that there would be an upregulation in patients with hypersensitivity disorders.

The results showed that TRPV1 mRNA from SU trigonal mucosa was significantly higher than control trigonal mucosa or SU bladder body mucosa. In contrast, in DO patients, there was no difference between trigonal mucosa and body mucosa. TRPV1 mRNA expressed in SU trigonal mucosa was significantly inversely correlated with the bladder volume at first sensation of filling during cystometry. No such relationship was seen for DO trigonal mucosa. Bladder body mucosa failed to show changes in women with disease versus controls.

The authors conclude that their data is in line with a role for TRPV1 as a sensory integrator of chemical, physical, or inflammatory stimuli in the storage phase of bladder filling. Thus, there is a scientific basis to pursue the therapeutic use of vanilloids in disorders manifested by bladder hypersensitivity and urgency, despite failure of resiniferatoxin in initial phase 2 trials for interstitial cystitis.

Lu Liu, Kylie J. Mansfield, Ika Kristiana, Kenneth J. Vaux, Richard J. Millard, Elizabeth Burcher

Neurourology and Urodynamics: Early View

Written by Philip M. Hanno, MD, a Contributing Editor with UroToday.

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