Analgesic effect of metorphamide on skin pain and visceral pain

Skin pain model (mouse hot plate test and rabbit potassium iontophoretic colorimetry) and visceral pain model (rabbit splanchnic nerve stimulation test) were used to measure the analgesia of metorphamide (MET), an endogenous opioid peptide isolated recently from bovine caudate nucleus and human pheochromocytoma tumor. MET elicited a potent analgesia in both models injected intracerebroventricularly (icv). The ED50 for MET icv on skin pain model were 0.86+/-0.35 nmol/mouse and 65+/-33 nmol/rabbit; while ED50 for morphine were 0.42+/-0.13 nmol/mouse and 20+/-7 nmol/rabbit, respectively. The analgesic effect of MET was slightly milder and shorter than that of morphine. The analgesic effect of MET was prevented by naloxone (1 mg/kg, ip 10 min before icv MET in mice) and anloxonazine (50 microg, icv 22 h before icv of MET in rabbits), a selective blocker of mu 1 opiate receptor, indicating that the analgesic effect of MET is mainly mediated by mu 1 opiate binding site. Bestatin, an inhibitor of aminopeptidase, potentiated the analgesic effect of MET. It suggests that aminopeptidases play an important role in MET degradation in vivo.