Optical nerve stimulation (ONS) is being explored as an alternative to electrical nerve stimulation (ENS) for use as an intra-operative diagnostic method for identification and preservation of prostate cavernous nerves (CNs) during radical prostatectomy. Nerve priming and fatigue studies were performed to further characterize CNs and provide insight into the different ONS and ENS mechanisms. ONS studies were conducted using a 1455-nm diode laser, coupled to fiber optic probe, and delivering a collimated, 1-mm-diameter laser spot on CNs. For nerve priming studies, laser power was escalated in 5 mW increments (15 - 60 mW) with each stimulation lasting 15 s, until a strong ICP response was observed, and then power was similarly de-escalated. For ONS fatigue studies, a constant laser power was delivered for a period of 10 min. ENS studies were conducted for comparison, with standard parameters (4 V, 5 ms, 16 Hz) for fatigue studies (10 min. duration), but incrementally increasing/decreasing voltage (0.1 - 4.0 V) for priming studies with 15 s stimulations. ONS threshold was approximately 20% higher during initial escalating laser power steps (6.4 W/cm2) than in subsequently de-escalating laser power steps (5.1 W/cm2), demonstrating a nerve priming effect. Evidence of nerve priming during ENS was not observed. For nerve fatigue studies, ONS of CNs showed a peak ICP response at about 60 s, followed by a gradual decay in ICP, while ENS maintained a strong, but cyclical ICP. Nerve priming may allow repetitive ONS of CNs at lower and hence safer laser power settings. Both nerve priming and fatigue studies revealed different mechanisms for ONS and ENS.