The Journal of Neuroscience, November 15, 2001, 21(22):9001-9008
Spinal Prostaglandins Are Involved in the Development But Not the
Maintenance of Inflammation-Induced Spinal Hyperexcitability
Enrique
Vasquez,
Karl-Jürgen
Bär,
Andrea
Ebersberger,
Barbara
Klein,
Horacio
Vanegas, and
Hans-Georg
Schaible
Institut für Physiologie I, Universität Jena, D-07740
Jena, Germany
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 E2
(PGE2) 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 PGE2 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.
Key words:
central sensitization; glutamate; pain; nociception; NSAID; prostaglandin
Copyright © 2001 Society for Neuroscience 0270-6474/01/21229001-08$05.00/0
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