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Human hemokinin-1 (h HK-1) and its truncated form h HK-1(4-11) are mammalian tachykinin peptides encoded by the recently identified TAC4 gene in human, and the biological functions of these peptides have not been well investigated. In the present study, an attempt has been made to investigate the effects and mechanisms of action of h HK-1 and h HK-1(4-11) in pain modulation at the supraspinal level in mice using the tail immersion test. Intracerebroventricular (i.c.v.) administration of h HK-1 (0.3, 1, 3 and 6nmol/mouse) produced a dose- and time-related antinociceptive effect. This effect was significantly antagonized by the NK₁ receptor antagonist SR140333, but not by the NK₂ receptor antagonist SR48968, indicating that the analgesic effect induced by i.c.v. h HK-1 is mediated through the activation of NK₁ receptors. Interestingly, naloxone, β-funaltrexamine and naloxonazine, but not naltrindole and nor …