The current study evaluated the effects of
hemopressin (HP) on
pain modulation by endokinin A/B (EKA/B) and endokinin C/D (EKC/
D) at the supraspinal level in mice. Intracerebroventricular administration of HP (10 nmol) fully antagonized the
hyperalgesia induced by EKA/B (10, 30, and 100 pmol), and induced a dose-dependent potent
analgesic effect. HP at different concentrations (10 pmol, 100 pmol, and 1 nmol) showed varying effects on the
analgesic effect of EKA/
B (3 nmol). HP extended the duration of the
analgesic effect of EKC/D (3 nmol). Moreover, HP at different concentrations (10 pmol, 5 pmol, 1 pmol, and 100 fmol) co-administered with EKC/D (30 pmol) induced significant
analgesia at two different time points: 5 min and 50 min. To investigate the antinociceptive mechanism, we used
SR140333B and
SR142801. HP (1 pmol) potentiated the
analgesic effect of
SR140333B (100 pmol)+EKA/B (30 pmol) in 5-10 min, while HP (100 pmol) had no effect in the
analgesia induced by
SR140333B (3 nmol)+EKA/
B (3 nmol). HP (1 nmol) fully inhibited the
analgesic effect of
SR140333B (3 nmol)+EKC/D (3 nmol) or
SR142801 (3 nmol)+EKC/D (3 nmol). HP (1 pmol) weakened the
analgesic effect of
SR142801 (100 pmol)+EKA/B (30 pmol), but HP (100pmol) strengthened the
analgesic effect of
SR142801 (3 nmol)+EKA/
B (3 nmol). These findings may pave the way for a new strategy on investigating the interaction between
tachykinins and
opioids on
pain modulation.