Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China.
Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing 400037, China.
Biochem Pharmacol. 2021 Jan;183:114340. doi: 10.1016/j.bcp.2020.114340. Epub 2020 Nov 13.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a type of chronic bladder inflammation characterized by increased voiding frequency, urgency and pelvic pain. The sensitization of bladder afferents is widely regarded as one of the pathophysiological changes in the development of IC/BPS. There is evidence that adenosine A receptors are involved in regulating the sensitization of sensory afferents. However, the effect of adenosine A receptors on cystitis remains unknown. In the present study, a rat model of chronic cystitis was established by intraperitoneal injection with cyclophosphamide (CYP). Cystometry and behavioral tests were performed to investigate bladder micturition function and nociceptive pain. The rats with chronic cystitis showed symptoms of bladder overactivity, characterized by an increase in bladder voiding frequency and voiding pressure. CYP treatment significantly increased the expression of the A receptor in bladder afferent fibers and dorsal root ganglion (DRG) neurons. The A receptor antagonist ZM241385 prevented bladder overactivity and hyperalgesia elicited by CYP-induced cystitis. In addition, the A receptor and TRPV1 were coexpressed on DRG neurons. The TRPV1 antagonist capsazepine blocked bladder overactivity induced by the A receptor agonist CGS21680. In contrast, ZM241385 significantly inhibited the capsaicin-induced increase in intracellular calcium concentration in DRG neurons. These results suggest that suppression of adenosine A receptors in bladder afferents alleviates bladder overactivity and hyperalgesia elicited by CYP-induced cystitis in rats by inhibiting TRPV1, indicating that the adenosine A receptor in bladder afferents is a potential therapeutic target for the treatment of IC/BPS.
间质性膀胱炎/膀胱疼痛综合征（IC/BPS）是一种慢性膀胱炎症，其特征为排尿频率增加、尿急和盆腔疼痛。膀胱传入纤维的敏化被广泛认为是 IC/BPS 发展的一种病理生理变化。有证据表明，腺苷 A 受体参与调节感觉传入纤维的敏化。然而，腺苷 A 受体对膀胱炎的影响尚不清楚。在本研究中，通过腹腔注射环磷酰胺（CYP）建立了大鼠慢性膀胱炎模型。进行膀胱测压和行为学测试，以研究膀胱排尿功能和疼痛感受。慢性膀胱炎大鼠表现出膀胱过度活动的症状，表现为膀胱排空频率和排空压力增加。CYP 处理显著增加了膀胱传入纤维和背根神经节（DRG）神经元中 A 受体的表达。A 受体拮抗剂 ZM241385 可预防 CYP 诱导的膀胱炎引起的膀胱过度活动和痛觉过敏。此外，A 受体和 TRPV1 在 DRG 神经元上共表达。TRPV1 拮抗剂辣椒素阻断了由 A 受体激动剂 CGS21680 引起的膀胱过度活动。相反，ZM241385 显著抑制了辣椒素诱导的 DRG 神经元细胞内钙离子浓度的增加。这些结果表明，抑制膀胱传入纤维中的腺苷 A 受体通过抑制 TRPV1 缓解 CYP 诱导的膀胱炎引起的大鼠膀胱过度活动和痛觉过敏，表明膀胱传入纤维中的腺苷 A 受体是治疗 IC/BPS 的潜在治疗靶点。
