Pain is a complex and subjective experience. Previous studies have shown that 
mice lacking the dopamine D3 receptor (D3RKO) exhibit hypoalgesia, indicating a 
role of the D3 receptor in modulation of nociception. Given that there are sex 
differences in pain perception, there may be differences in responses to 
nociceptive stimuli between male and female D3RKO mice. In the current study, we 
examined the role of the D3 receptor in modulating nociception in male and 
female D3RKO mice. Acute thermal pain was modeled by hot-plate test. This test 
was performed at different temperatures including 52°C, 55°C, and 58°C. The von 
Frey hair test was applied to evaluate mechanical pain. And persistent pain 
produced by peripheral tissue injury and inflammation was modeled by formalin 
test. In the hot-plate test, compared with wild-type (WT) mice, D3RKO mice 
generally exhibited longer latencies at each of the three temperatures. 
Specially, male D3RKO mice showed hypoalgesia compared with male WT mice when 
the temperature was 55°C, while for the female mice, there was a statistical 
difference between genotypes when the test condition was 52°C. In the von Frey 
hair test, both male and female D3RKO mice exhibited hypoalgesia. In the 
formalin test, the male D3RKO mice displayed a similar nociceptive behavior as 
their sex-matched WT littermates, whereas significantly depressed late-phase 
formalin-induced nociceptive behaviors were observed in the female mutants. 
These findings indicated that the D3 receptor affects nociceptive behaviors in a 
sex-specific manner and that its absence induces more analgesic behavior in the 
female knockout mice. © 2016 Wiley Periodicals, Inc.