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

The hypothesis that the nociceptive state and opiate-induced antinociception are generally regulated by Ca2+ brain levels has been tested. In this context, the effects of intracerebroventricular injections of CaCl2 (0.1-0.5 mumol), D600 (5.0-10.0 micrograms) and EGTA (0.5-1.0 mumol) on ethylketocyclazocine (EKC), ketocyclazocine (KC), Mr-2033, 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 kappa-agonists: EKC, KC and Mr-2033, whilst the activities of PTC, BMC and SKF 10,047 remained unchanged. CaCl2 readily blocked the activities of all benzomorphans tested except that of SKF 10,047 against which CaCl2 was less effective. In addition a dose-related hyperalgesia was observed when CaCl2 was given alone. Although the results obtained from the kappa-agonists and CaCl2 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.