To assess the penile sensory pathway abnormalities of the patients with primary premature ejaculation (PPE) and effects of prilocaine-lidocaine (PLA) cream, we enrolled 82 PPE patients and 34 normal potent male volunteers. Somatosensory evoked potentials of dorsal nerve (DNSEP) and glans penis (GPSEP) were performed in each subject. In addition, among the 82 patients, 60 were selected and randomly divided into PLA and placebo subgroups, each with 30 patients. Cream was applied evenly on the glans penis for 10 min and washed off just before DNSEP and GPSEP were repeatedly measured. Mean latencies of DNSEP and GPSPE were both remarkably shorter in the patients than those in the normal potent men (P<0.001, both). Compared with the control group, the mean amplitudes of GPSEP were significantly greater in the patient group (P<0.001), but not considerably on the amplitudes of DNSEP (P=0.229). After cream application, the latencies and amplitudes of both DNSEP and GPSEP were significantly prolonged and reduced, respectively, in the PLA cream subgroup (P<0.001, all). These results showed that hyperexcitable ejaculatory reflex neurological factor was linked to PPE, because of hypersensitivity of the penile, accelerated conduction and cortical amplification of the genital stimuli. The PLA cream could delay sensory latency and decrease glans penile hyperexcitability, which may be the mechanism for PPE treatment.