Dual effect of cAMP on the writhing response in mice

The intraperitoneal injection of agents that increase the intracellular level of cyclic AMP (cAMP), reduced significantly the number of writhes induced by acetic acid and zymosan in mice. However, dibutyryl cyclic AMP (Db-cAMP) induced a dual response: (a) low doses caused antinociception, and (b) a high dose potentiated the nociceptive effect of a low concentration of acetic acid. High doses of Db-cAMP also reversed the antinociceptive effect of dexamethasone and the depletion of resident peritoneal cells. We also demonstrated that a low dose of Db-cAMP, forskolin or dexamethasone inhibited the production of tumor necrosis factor-alpha and interleukin-1 beta by macrophages stimulated by zymosan. In conclusion, this study suggests that cAMP has a dual effect in the writhing model: an antinociceptive effect due to its modulatory action on resident peritoneal cells, thus, reducing the synthesis of mediators involved in the nociceptive response, and a nociceptive effect by directly sensitizing the nociceptive neuron.