Augé Céline, Vogt Mathieu, Martin Vincent, Lezmi Stéphane, Gamé Xavier, Lluel Philippe, Maignel Jacquie
Urosphere, Toulouse, France.
Ipsen Innovation, 5 Avenue du Canada, 91940, Les Ulis, France.
J Neural Transm (Vienna). 2025 Mar 15. doi: 10.1007/s00702-025-02906-2.
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), 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.
虽然间质性膀胱炎合并膀胱疼痛综合征（IC/BPS）的治疗效果仍然不佳，但已发表的临床证据表明，膀胱逼尿肌内注射A型肉毒毒素（天然A型肉毒杆菌神经毒素（BoNT/A））对IC/BPS有效。然而，由于膀胱灌注可能是一种更安全、更方便的给药途径，我们旨在研究无针注射BoNT/A在IC/BPS啮齿动物模型中的效果。使用环磷酰胺（CYP）诱导大鼠发生IC/BPS。所产生的症状模拟了人类非溃疡性IC/BPS的主要关键特征。通过尿道将阿泊肉毒毒素A（aboBoNT-A）或临床使用的参考化合物作为单次膀胱内给药注入膀胱。在诱导膀胱疼痛前后，使用von Frey细丝在腹部水平评估内脏痛觉过敏和痛觉超敏。还使用免疫组织化学（IHC）对膀胱中BoNT/A切割的SNAP25（c-SNAP25）、总SNAP25（SNAP25）、β-3微管蛋白和降钙素基因相关肽（CGRP）的水平以及组织病理学损伤进行了定量分析。aboBoNT-A在高达30 U/大鼠的剂量下耐受性良好。aboBoNT-A给药后，痛觉过敏和痛觉超敏显著降低，与参考药物相比疗效更高。3个aboBoNT-A组的逼尿肌中c-SNAP25的IHC水平较低且相似。CYP和aboBoNT-A均未引起SNAP25、β-3微管蛋白或CGRP含量的任何变化。一些CYP诱导的组织病理学损伤在aboBoNT-A作用下有改善趋势。aboBoNT-A显示出镇痛特性，有望转化为更好的内脏痛治疗方法。有趣的是，膀胱内（无针）给药似乎是IC/BPS患者肉毒毒素治疗的一种有前景且可重复的途径。
