A needleless or high-pressure injection system for injecting treatment or therapeutic fluid to tissue of the lower urinary tract, such as the prostate or bladder, is provided. The systems or devices can release the therapeutic fluid or “injectate” at high-pressure out of one or more orifices at the end of an elongate shaft inserted into the urethra. Various embodiments can include a pneumatic or fully-pneumatic system adapted to selectively release the high-pressure injectate, while also providing firing or triggering protection.