Effects of intravesical instillation of ATP on rat bladder primary afferent activity and its relationship with capsaicin-sensitivity
Faculty of Medicine and Health Sciences
Neurourology and urodynamics. - New York
, p. 163-168
University of Antwerp
Aims 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. Methods Female SpragueDawley 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. Results 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. Conclusions 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.