Aim of our studies is to characterize the role of spinal prostaglandins during different states of knee joint inflammation. The development and maintenance of hyperexcitability of nociceptive spinal cord neurons during inflammation was assessed by electrophysiological recordings. While spinal indomethacin (and/or diclofenac) attenuated the hyperexcitability of the neurons during development of inflammation it had no effect on the neuronal responses to mechanical stimulation of the knee, ankle and paw during acute and chronic inflammation (day 1, 3 and 21). In addition, spinally applied agonists at prostaglandin EP1, 2 and 4 receptors rendered neurons hyperexcitable in normal rats but did not change neuronal activity in rats with knee inflammation. Thus, the presence of PGE2 is mainly important for the development of inflammation but less for its maintenance. However, a selective COX2 inhibitor prevented the development of spinal hyperexcitability and reduced neuronal activity on day 1 and 21 of inflammation raising the possibility that COX2 inhibitors also act by mechanisms other than inhibition of prostaglandin synthesis, e.g the endocannabinoid metabolism.