kaolinite and Hyperesthesia

Prostaglandins (PGs) are local mediators of several functions in the CNS. Both 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 mechanosensory information was herein investigated. In anesthetized rats, the discharges of spinal nociceptive neurons with input from the knee joint were extracellularly recorded. Topical administration of prostaglandin E(2) (PGE(2)) to the spinal cord facilitated the discharges and expanded the receptive field of dorsal horn neurons to innocuous and noxious pressure applied to the knee joint, the ankle, and the paw, thus mimicking inflammation-induced central sensitization. Conversely, topical administration of the PG synthesis inhibitor indomethacin to the spinal cord before and during development of knee joint inflammation attenuated the generation of inflammation-induced spinal 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. Thus, spinal PG synthesis is important for the induction and initial expression but not for the maintenance of spinal cord hyperexcitability. Spinal PGE(2) application facilitated dorsal horn neuronal firing elicited by ionophoretic delivery of NMDA, suggesting that an interaction of PGs and NMDA receptors may contribute to inflammation-induced central sensitization. However, after development of inflammation, spinal indomethacin failed to reduce responses to ionophoretic delivery of NMDA or AMPA, suggesting that such an interaction is not required for the maintenance of central sensitization.

Topics: Action Potentials; Administration, Topical; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Carrageenan; Dinoprostone; Excitatory Amino Acid Agonists; Hindlimb; Hyperesthesia; Indomethacin; Inflammation; Injections, Spinal; Iontophoresis; Joints; Kaolin; Male; N-Methylaspartate; Nociceptors; Physical Stimulation; Posterior Horn Cells; Prostaglandins; Rats; Rats, Wistar; Spinal Cord

Topics: Administration, Oral; Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Erythema; Female; Fever; Granuloma; Guinea Pigs; Hyperesthesia; Injections, Intravenous; Kaolin; Male; Mice; Peritonitis; Phenylbutazone; Pyrazoles; Rats; Terpenes; Ultraviolet Rays