Comparison of nociceptive behavior in prostaglandin E,F, D,prostacyclin and thromboxane receptor knockout mice

Antagonist at specific prostaglandin receptors might provide analgesia with a more favourable toxicity profile compared with cyclooxygenase inhibitors. We analyzed nociceptive responses in prostaglandin D, E, F, prostacyclin and thromboxane receptor knockout mice and mice deficient of cyclooxygenase 1 or 2 to evaluate the contribution of individual prostaglandin receptors for heat, mechanical and formalin‐evoked pain. None of the knockouts was uniformly protected from all of these pain stimuli but COX‐1 and EP4 receptor knockouts presented with reduced heat pain and EP3 receptor and COX‐2 knockout mice had reduced licking responses in the 2nd phase of the formalin assay. This was accompanied with reduced c‐Fos immunoreactivity in the spinal cord dorsal horn in EP3 knockouts. Oppositely, heat pain sensitivity was increased in FP, EP1 and EP1+3 double mutant mice possibly due to a loss of FP or EP1 receptor mediated central control of thermal pain sensitivity. Deficiency of either EP2 or DP1 was associated with increased formalin‐evoked flinching responses and c‐Fos IR in dorsal horn neurons suggesting facilitated spinal cord pain reflex circuity. Thromboxane and prostacyclin receptor knockout mice showed normal pain behavior in all tests. The results suggest a differential, pain‐stimulus and site‐specific contribution of specific PG‐receptors for the processing of the nociceptive stimuli, a differential modulation of nociceptive responses by COX‐1 and COX‐2 derived prostaglandins and compensatory and/or developmental adaptations in mice lacking specific PG receptors.