Background: This study evaluated the effects of the imidazoline I2 receptor (I2R) agonist 2BFI on lower urinary tract dysfunction (LUTD) in a mouse spinal cord injury (SCI) model. Methods: Female mice were divided into three groups: spinal intact (SI), SCI with vehicle, and SCI with 2BFI beginning two weeks post-injury. SCI was induced by complete Th8–9 spinal transection. Four weeks after SCI, conscious cystometrograms (CMG) and external urethral sphincter (EUS) electromyography (EMG) were recorded. L6–S1 dorsal root ganglia (DRG) were collected for qPCR analysis of TRPV1, TNF-α, and iNOS. In a separate group of animals, intrathecal (i.t.) 2BFI was tested during CMG/EMG in SCI. Organ bath studies assessed 2BFI-induced relaxation in bladder strips precontracted with KCl or carbachol. Results: SCI mice showed increased non-voiding contractions (NVCs) and reduced voiding efficiency versus SI. 2BFI significantly decreased NVCs, improved voiding efficiency, and prolonged EUS relaxation evident as reduced EMG activity compared with vehicle. SCI-induced upregulation of TRPV1, TNF-α, and iNOS in DRG was significantly attenuated by 2BFI. I.t. 2BFI reduced residual urine and NVCs and increased EUS relaxation in SCI mice. In organ baths, 2BFI produced significant relaxation of precontracted bladder strips from both SI and SCI mice. Conclusion: I2R activation in the lumbosacral spinal cord and bladder may provide an effective therapeutic strategy for SCI-induced LUTD.
Hashimoto et al. (Sat,) studied this question.