Involvement of 5-hydroxytryptamine and bradykinin in the hyperalgesia induced in rats by collagenase from Clostridium histolyticum

The involvement of bradykinin, 5-hydroxytryptamine, substance P and prostanoids in the hyperalgesia elicited by collagenase in rat paw was investigated. Collagenase (100 mu g) induced a slight hyperalgesia in kininogen deficient rats in comparison with the behavioural response obtained in normal rats. Lisinopril (10(-5) M), and angiotensin-converting enzyme inhibitor, increased the duration of the hyperalgesia elicited in normal rats. Ondansetron (0.5 to 5 mu mol/kg), a 5-HT3 antagonist, suppressed the hyperalgesia as did methysergide (1.1 to 11 mu mol/kg), a mixed 5-HT1 and 5-HT2 receptor antagonist. However, the hyperalgesia was not modified by RP 67580 (1.8 to 18 mu mol/kg), a NK1 receptor antagonist, and was only slightly delayed by indomethacin (2 mg/kg), a cyclo-oxygenase inhibitor. The oedema-promoting effect of 5-HT (6 nmol) was inhibited by methysergide but not by ondansetron. The swelling induced by collagenase in rat paw was reduced by methysergide but not by ondansetron. We conclude that the behavioural response induced by collagenase depends on an interactions between bradykinin and 5-HT. Prostanoids play a minor role in the beginning of the reaction whereas substance P is not significantly involved in this hyperalgesia.