Intrathecal administration of prostaglandin E2 causes sensitization of the primary afferent neuron via the spinal release of glutamate

Inflamm Res. 1996 Oct;45(10):499-502. doi: 10.1007/BF02311085.


Objective and design: The present investigation was aimed at assessing the involvement of primary sensory neurons in the hyperalgesia induced by the intrathecal injection of PGE2, as well as whether the hyperalgesic effect was due to the spinal release of glutamate.

Material: Male Wistar rats were used.

Methods: Hyperalgesia was measured using the rat paw pressure test.

Results: Intrathecal PGE2 (2.5-50 ng/rat) administration caused a dose-dependent hyperalgesia in both paws. Ipsilateral intraplantar injections of morphine (0.5-8 micrograms/paw) or SNAP (S-nitroso-N-acetyl-D,L-penicillamine, 50-200) micrograms/paw) dose-dependently antagonized spinally-induced PGE2 hyperalgesia (ANOVA, p < 0.001). Their antinociceptive effects were confirmed to be peripheral by abolition following pretreatment of the paws with L-NMMA (NG-monomethyl-L-arginine monoacetate), 50 micrograms/paw or with methylene blue (500 micrograms/paw). The spinally-induced PGE2 hyperalgesia was antagonized by intrathecal injections (9 micrograms) of AP5 (2-amino-5-phosphonopentanoate/2-amino-5) a selective NMDA receptor antagonist.

Conclusions: Intrathecal administration of PGE2 seems to cause hyperalgesia by spinal sensitization of the primary afferent neuron through the release of glutamate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Dinoprostone / administration & dosage
  • Dinoprostone / pharmacology*
  • Glutamic Acid / metabolism*
  • Hyperalgesia / etiology*
  • Injections, Spinal
  • Male
  • Neurons, Afferent / drug effects*
  • Neurons, Afferent / metabolism
  • Penicillamine / analogs & derivatives
  • Penicillamine / pharmacology
  • Rats
  • Rats, Wistar
  • S-Nitroso-N-Acetylpenicillamine
  • Spinal Cord / drug effects*
  • omega-N-Methylarginine / pharmacology


  • omega-N-Methylarginine
  • Glutamic Acid
  • 2-Amino-5-phosphonovalerate
  • S-Nitroso-N-Acetylpenicillamine
  • Penicillamine
  • Dinoprostone