Formalin-induced nociceptive behavior and edema: involvement of multiple peripheral 5-hydroxytryptamine receptor subtypes
Section snippets
Animals
All experiments were conducted on male Sprague–Dawley rats (Charles River, Quebec, Canada) weighing between 100 and 150 g. The animals were housed in groups of two to four in the animal care facility and maintained on a 12 h light/dark cycle with rat chow and water available ad libitum. A minimum 24 h acclimatization period was allowed after shipment to the facility. On the day of testing, rats were removed from the animal care facility to the testing area at least 1 h before testing. Each
Formalin dose–response relationship
Flinching behavior following formalin injection was determined for formalin concentrations of 0.5–5.0% and compared to saline. Only the higher concentrations of formalin (2.5% and 5.0%) produced flinching in phase 1 that was significantly greater (P<0.05) than a saline injection (Fig. 1A), whereas the flinching response to formalin was significantly greater than saline control in phase 2 (P<0.05) at all formalin concentrations tested (Fig. 1B). The lowest concentration of formalin tested
Discussion
This study, which used the low concentration formalin (0.5%) model to detect pronociceptive actions of inflammatory mediators, confirmed the involvement of 5-HT in the development of inflammation following injection of subcutaneous formalin in the rat hindpaw. As well as confirming the role of peripheral 5-HT1 and 5-HT3 receptors in nociception, this is the first study to suggest involvement of peripheral 5-HT4 receptors in augmentation of the pain signal. Activation of peripheral 5-HT2
Conclusions
This study shows 5-HT to be a key component of the inflammatory response to subcutaneous formalin injection in the rat. Multiple 5-HT receptor subtypes, including the 5-HT4 receptor, are involved. Peripherally active 5-HT4 receptor antagonists may represent a novel approach to analgesia in conditions of acute inflammation.
Acknowledgements
This work was supported by the Medical Research Council of Canada through a grant to J.S. and by the Canadian Anaesthetists' Society and Janssen Pharmaceutica through a fellowship to G.D.
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