Effects of elevated calcium and calcium antagonists on 6,7-benzomorphan-induced analgesia

Abstract

The hypothesis that the nociceptive state and opiate-induced antinociception are generally regulated by Ca 2+ brain levels has been tested. In this context, the effects of intracerebroventricular injections of CaCl 2 (0.1–0.5 μmol), D600 (5.0–10.0 μg) and EGTA (0.5–1.0 μmol) on ethylketocyclazocine (EKC), ketocyclazocine (KC), Mr-2023, pentazocine (PTC), bremazocine (BMC) and SKF 10,047-induced antinociception were investigated in the mouse tail immersion test. Simultaneous treatment with either D600 or EGTA resulted in a significant and dose-related enhancement in the activities of the κ-agonists; EKC, KC and Mr-2033, whilst the activities of PTC, BMC and SKF 10,047 remained unchanged. CaCl 2 readily blocked the activities of all benzomorphans tested except that of SKF 10,047 against which CaCl 2 was less effective. In addition a dose-related hyperalgesia was observed when CaCl 2 was given alone. Although the results obtained from the κ-agonists and CaCl 2 per se support the hypothesis in question, data obtained from PTC, BMC and SKF 10,047 tends to oppose it. Additionally the present results taken together indirectly substantiate the notion that benzomorphan-induced analgesia may involve different opiate-sensitive neuronal substrates.