Different effect of sumatriptan in models of thermal, chemical or cephalalgic pain, in rats

Triptans have represented a real progress in the acute therapy of migraine. The beneficial effect of this new class of drugs depends on their agonist activity on 5-HT1B/1D/1F receptors. However, some sparse experimental data have been produced showing that triptans may have a non specific, systemic analgesic activity in virtue of other mechanisms of action. Aim of our present study was to evaluate the effect of sumatriptan (chosen as the lead of this class) in two standard algesimetric tests and in an animal model of cephalalgia. Adult male Wistar rats were used. The response to a thermal painful stimulus was evaluated by means of the hot-plate test (temperature of the plate: 54±0.4°C; cut-off time: 30 s); the response to a chemical painful stimulus was evaluated by means of the abdominal constriction test (writhing test) (intraperitoneal injection of 2 ml 0.5% acetic acid); cephalalgia was produced by injecting bradykinin (8 µg in a volume of 8 µl) into a common carotid artery. Sumatriptan was subcutaneously (s.c.) injected at the doses of 4, 8, 24 and 42 mg/kg. 10 min before testing. Morphine (5 or 10 mg/kg s.c.) and indomethacin (10 mg/kg per os), used as standard analgesic drugs, were administered 20 or 30 min, respectively, before testing. Groups of 8-12 rats per dose were used; each rat was used for only one treatment. Control rats received by the same routes identical volumes of saline. Results were analyzed by one-way ANOVA followed by Student-Newman-Keuls’ test, or by Friedman test followed by Mann-Withney U test, or by Chi-square test, where appropriate. Sumatriptan had no analgesic activity at any of the doses used either in the hot-plate test [F(7,80)=11.82, P=0.000] or in the writhing test [F(7,63)=17.37, P=0.000], while morphine and indomethacin were significantly effective. On the other hand, sumatriptan, at the doses of 24 and 42 mg/kg, significantly reduced the consequences of the intracarotid injection of bradikinin (vocalization, tachypnea, ECG alterations) [x 2=8.55, P=0.014]. These data demonstrate that sumatriptan is significantly effective in a reliable animal model of cephalalgia, while being devoid – at the same doses and in the same animal species – of any systemic analgesic activity.