Effects of endokinin A/B and endokinin C/D on the antinociception properties of hemopressin in mice

Abstract

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.