To further understand the mechanism of analgesic activity and structural requirements of pyrrolidinoindoline alkaloids identified in Psychotria colorata, we here report the analgesic activity of the trimer hodgkinsine on thermal and chemical models of analgesia. Results show that hodgkinsine produces a dose-dependent naloxone reversible analgesic effect in thermal models of nociception, suggesting that activation of opioid receptors participates in hodgkinsine's mode of action. Hodgkinsine shows a potent dose-dependent analgesic activity against capsaicin-induced pain, indicating the participation of NMDA receptors in hodgkinsine-induced analgesia. Such a dual mechanism of action may be of interest for developing innovative analgesics.