FORMALIN-INDUCED NOCICEPTIVE BEHAVIOR AND EDEMA - INVOLVEMENT OF MULTIPLE PERIPHERAL 5-HYDROXYTRYPTAMINE RECEPTOR SUBTYPES

The role of 5-hydroxytryptamine and its receptor subtypes in the devel opment of acute inflammation was investigated using the rat paw formal in test as a model for pain (measured by flinching behavior) and edema formation (measured by plethysmometry). The role of endogenously rele ased 5-hydroxytryptamine was assessed using 5-hydroxytryptamine recept or subtype-selective antagonists co-injected with 2.5% formalin, while the receptor subtypes involved in the inflammatory process were furth er defined by co-injection of 5-hydroxytryptamine or 5-hydroxytryptami ne receptor subtype-selective agonists with 0.5% formalin in anticipat ion of an augmented response. When co-administered with 2.5% formalin, propranolol, tropisetron or GR113808A, but not ketanserin, effectivel y blocked nociceptive behavior. In the presence of 0.5% formalin, 5-ca rboxamidotryptamine, 1-(m-chlorophenyl) biguanide or 5-methoxytryptami ne, but not )-1-4-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane, augment ed the flinching response. These data suggest involvement of 5-hydroxy tryptamine(1), 5-hydroxytryptamine(3) and 5-hydroxytryptamine(4) recep tors in peripheral nociception. There may be some dissociation of noci ception and edema formation, since no single 5-hydroxytryptamine recep tor antagonist inhibited edema formation with 2.5% formalin; however, with 0.5% formalin, edema formation was enhanced by co-administration of 5-hydroxytryptamine, 5-carboxamidotryptamine, -)-1-4-(4-iodo-2,5-di methoxyphenyl)-2-aminopropane or 5-methoxytryptamine, but not 1-(m-chl orophenyl) biguanide. These data suggest involvement of 5-hydroxytrypt amine(1), 5-hydroxytryptamine(2) and possibly 5-hydroxytryptamine(4) r eceptors in edema formation. These results confirm the involvement of 5-hydroxytryptamine(1) and 5-hydroxytryptamine(3) receptor subtypes in peripheral nociception associated with acute inflammation and further suggest an involvement of the more recently characterized 5-hydroxytr yptamine(4) receptor in this process. There appears to be a dissociati on in 5-hydroxytryptamine receptors involved in peripheral nociception and edema formation. (C) 1997 IBRO. Published by Elsevier Science Ltd .