*5.2. Disrupt Barrier*

#### 5.2.1. Protamine Sulfate

Protamine sulfate, an arginine-rich protein, can increase permeability in the apical membrane to both cations and anions by altering the membrane conductance in different concentrations and by damage to the surface of the bladder mucosa [16,17]. In addition, protamine sulfate also has analgesic effects, tissue-protective effects, and pro-inflammatory response suppression for relieving bladder pain in mice [18].

In a study, rats with spinal cord injuries received 1 mL of 1% protamine sulfate bladder instillation, followed by 1 mL of onaBoNTA (20 U). By using this procedure, Khera et al. reported that onaBoNTA could inhibit vesical sensory mechanisms but could not alter bladder motor function in rats. These results denoted that onaBoNTA could not penetrate across the urothelium into detrusor muscle, even after the urothelium was disrupted by protamine sulfate instillation [13].
