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

Abstract

The involvement of bradykinin, 5-hydroxytryptamine, substance P and prostanoids in the hyperalgesia elicited by collagenase in rat paw was investigated. Collagenase (100μg) induced a slight hyperalgesia in kininogen deficient rats in comparison with the behavioural response obtained in normal rats. Lisinopril (10^–5M), and angiotensin-converting enzyme inhibitor, increased the duration of the hyperalgesia elicited in normal rats. Ondansetron (0.5 to 5μmol/kg), a 5-HT₃ antagonist, suppressed the hyperalgesia as did methysergide (1.1 to 11μmol/kg), a mixed 5-HT₁ and 5-HT₂ receptor antagonist. However, the hyperalgesia was not modified by RP67580 (1.8 to 18μmol/kg), a NK₁ receptor antagonist, and was only slightly delayed by indomethacin (2mg/kg), a cyclo-oxygenase inhibitor.

The oedema-promoting effect of 5-HT (6nmol) 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 reponse 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.