Antinociceptive properties of intravesical/needle-free administration of abobotulinumtoxinA in a rodent model of chronic visceral pain: in vivo and histological evidence.

Abstract

While interstitial cystitis along with bladder pain syndrome (IC/BPS) is still poorly treated, published clinical evidence suggests that onabotulinumtoxinA (natural botulinum neurotoxin type A (BoNT/A)) intradetrusor injections is efficient in IC/BPS. However, as bladder instillation could be a safer and more convenient administration route, we aimed to investigate the effect of BoNT/A needle-free administration in an IC/BPS rodent model. Cyclophosphamide (CYP) was used to induce IC/BPS in rats. The resulting symptoms mimicked the main key features of human non-ulcerative IC/BPS. AbobotulinumtoxinA (aboBoNT-A) or reference compounds used in the clinic were delivered as a single intravesical administration into the bladder via the urethra. Visceral allodynia and hyperalgesia were assessed at the abdominal level with von Frey filaments before and after bladder pain induction. The levels of BoNT/A-cleaved SNAP25 (c-SNAP25), total SNAP25 (SNAP25^N-ter), beta-3 tubulin and CGRP in bladders were also quantified using immunohistochemistry (IHC), as well as the histopathological lesions. AboBoNT-A was well tolerated up to 30 U/rat. Allodynia and hyperalgesia were significantly decreased after aboBoNT-A dosing, with higher efficacy compared to references. c-SNAP25 IHC levels were low and similar in the detrusor for the 3 aboBoNT-A groups. Neither CYP or aboBoNT-A induced any change in the amount of SNAP25, beta-3 tubulin or CGRP. Some CYP-induced histopathological lesions showed a trend in improvement under aboBoNT-A. AboBoNT-A displayed analgesic properties that could translate into better therapies for visceral pain. Interestingly, intravesical (needle-free) administration seems like a promising and reproducible route for botulinum toxin therapy in patients with IC/BPS.