Effects of intravesical instillation of ATP on rat bladder primary afferent activity and its relationship with capsaicin‐sensitivity

Abstract

Previous studies have suggested that ATP has a role in mechano-afferent transduction, at least partly mediated by nerves other than capsaicin (Cap)-sensitive nerves. We investigated the direct effect of ATP on single fiber activity (SFA) of the primary bladder afferent nerves and its relationship with Cap-sensitivity. Female Sprague-Dawley rats were used. On the basis of conduction velocities, SFA was grouped as Aδ- or C-fibers. First, SFA and intravesical pressure were measured during filling as the baseline. Then, Cap (10(-5) M) was instilled intravesically and the SFA response was monitored. To desensitize Cap-sensitive nerves, resiniferatoxin (RTX) (10(-6) M) was administered intravesically, and then Cap was again administered to confirm the desensitization effect. Thereafter, ATP (10(-3) M) or its vehicle was instilled intravesically and another filling cycles recorded. Thirty-two single afferent fibers were discriminated. Aδ-fibers did not respond to intravesical instillation of Cap, RTX or ATP. Based on Cap-sensitivity, C-fibers could be divided into two subtypes: Cap-sensitive (n=8) and Cap-insensitive (n=16). In the Cap-sensitive C-fibers, the response to bladder filling mostly disappeared after RTX desensitization, no matter if the bladder was filled with vehicle or ATP. On the other hand, in the Cap-insensitive C-fibers, even after RTX-treatment, the response was preserved and more enhanced when the bladder was filled with ATP compared to vehicle. Mechanosensitive bladder afferents can be classified as (1) Aδ-fibers, (2) Cap-insensitive, and (3) Cap-sensitive C-fibers. The activation of the bladder afferents induced by intravesical application of ATP is mediated mainly through Cap-insensitive C-fibers.