Spinal prostaglandins are involved in the development but not the maintenance of inflammation-induced spinal hyperexcitability

Prostaglandins (PGs) are local mediators of several functions in the CNS. B oth primary afferent neurons and intrinsic cells in the spinal cord produce PGs, with a marked upregulation during peripheral inflammation. Therefore, the significance of spinal PGs in the neuronal processing of mechanosensor y information was herein investigated. In anesthetized rats, the discharges of spinal nociceptive neurons with input from the knee joint were extracel lularly recorded. Topical administration of prostaglandin E-2 (PGE(2)) to t he spinal cord facilitated the discharges and expanded the receptive field of dorsal horn neurons to innocuous and noxious pressure applied to the kne e joint, the ankle, and the paw, thus mimicking inflammation-induced centra l sensitization. Conversely, topical administration of the PG synthesis inh ibitor indomethacin to the spinal cord before and during development of kne e joint inflammation attenuated the generation of inflammation-induced spin al neuronal hyperexcitability. However, after development of inflammation, the responses of spinal neurons to mechanical stimuli were only reduced by systemic indomethacin but not by indomethacin applied to the spinal cord. T hus, spinal PG synthesis is important for the induction and initial express ion but not for the maintenance of spinal cord hyperexcitability. Spinal PG E2 application facilitated dorsal horn neuronal firing elicited by ionophor etic delivery of NMDA, suggesting that an interaction of PGs and NMDA recep tors may contribute to inflammation-induced central sensitization. However, after development of inflammation, spinal indomethacin failed to reduce re sponses to ionophoretic delivery of NMDA or AMPA, suggesting that such an i nteraction is not required for the maintenance of central sensitization.