Gender, age and ethnic differences in pain perception have been reported in clinical and experimental research. However, it is not known whether cold and ischemia-induced pain models can explain ethnic-related variability in pain perception. The current study was designed to investigate the effect of ethnicity on pain perception in healthy Nigerians and to assess whether the variability in pain perception is dependent on the circulating level of β-Endorphin. One hundred and sixty healthy volunteers were randomly selected from the four main ethnic groups (Fulani, Hausa, Igbo and Yoruba) in Nigeria. There were 40 volunteers per group. The selected individuals were informed on what they should expect during the study after which their informed consents were requested. Questionnaires were used to obtain the socio-demographic and biodata of each of the consented volunteers. Cold, ischemia and cold+ischemia- induced pains were administered, after which the pain threshold and tolerance were estimated by monitoring the time (seconds) taken for pain to occur and the point at which the subject can no longer withstand the pain. Our results show that Igbo ethnic group has significantly lower threshold in cold-induced pain and significantly higher threshold/tolerance in ischemia-induced pain. No significant difference in pain threshold of all the four ethnic groups during cold+ischemia-induced pain. However, the pain tolerance was significantly higher in Igbo ethnic group when compared with Hausa, Fulani and Yoruba ethnic groups. In addition, the pain tolerance significantly decreased in Hausa and Yoruba compared to Fulani ethnic group, while the pain tolerance was significantly higher in Yoruba ethnic group compared with Hausa ethnic group. Also, the circulating β-Endorphin decreases in all the subjects. The present study demonstrates that ethnicity causes variability in pain perception and this is accompanied with alteration in circulating level of β-Endorphin