INVOLVEMENT OF 5-HYDROXYTRYPTAMINE AND BRADYKININ IN THE HYPERALGESIAINDUCED IN RATS BY COLLAGENASE FROM CLOSTRIDIUM-HISTOLYTICUM

The involvement of bradykinin, 5-hydroxytryptamine, substance P and pr ostanoids in the hyperalgesia elicited by collagenase in rat paw was i nvestigated. Collagenase (100 mu g) induced a slight hyperalgesia in k ininogen deficient rats in comparison with the behavioural response ob tained in normal rats. Lisinopril (10(-5) M), and angiotensin-converti ng enzyme inhibitor, increased the duration of the hyperalgesia elicit ed in normal rats. Ondansetron (0.5 to 5 mu mol/kg), a 5-HT3 antagonis t, suppressed the hyperalgesia as did methysergide (1.1 to 11 mu mol/k g), a mixed 5-HT1 and 5-HT2 receptor antagonist. However, the hyperalg esia was not modified by RP 67580 (1.8 to 18 mu mol/kg), a NK1 recepto r antagonist, and was only slightly delayed by indomethacin (2 mg/kg), a cyclo-oxygenase inhibitor. The oedema-promoting effect of 5-HT (6 n mol) was inhibited by methysergide but not by ondansetron. The swellin g induced by collagenase in rat paw was reduced by methysergide but no t by ondansetron. We conclude that the behavioural response induced by collagenase depends on an interactions between bradykinin and 5-HT. P rostanoids play a minor role in the beginning of the reaction whereas substance P is not significantly involved in this hyperalgesia.