N-Methyl-d-aspartate receptor antagonist d-AP5 prevents pertussis toxin-induced alterations in rat spinal cords by inhibiting increase in concentrations of spinal CSF excitatory amino acids and downregulation of glutamate transporters

Chih Shung Wong, Gong-Jhe Wu, Wu Fu Chen, Yen Hsuan Jean, Ching Hsien Hung, Chan Shing Lin, Shi Ying Huang, Zhi Hong Wen

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Recently, we found that intrathecal (i.t.) pertussis toxin (PTX) injection produces thermal hyperalgesia and is associated with increasing concentrations of excitatory amino acids (EAAs) in spinal cerebrospinal fluid (CSF) dialysates; a reduction in the antinociceptive effects of morphine and glutamate transporters (GTs) was also observed. The reduction in the morphine-induced analgesic effects is directly related to increased extracellular EAA levels, which are maintained by GTs at physiological levels. In this study, we aimed to examine the role of GT isoforms in thermal hyperalgesia, determine the EAA concentrations in CSF dialysates, and elucidate the role of N-methyl-d-aspartate (NMDA) receptors in PTX-induced reduction in the antinociceptive effects of morphine. Two i.t. catheters and one microdialysis probe were inserted into male Wistar rats: one catheter was used for PTX (1 μg) and morphine (10 μg) injection and the other was connected to an osmotic pump for NMDA receptor antagonist d-2-amino-5-phosphonopentanoic acid (d-AP5; 2 μg/h for 4 days) continuous infusion. The microdialysis probe was used to collect CSF dialysates for EAA measurements by high-performance liquid chromatography. Intrathecal morphine failed to produce antinociceptive effects in PTX-treated rats, and d-AP5 coinfusion prevented the PTX-induced reduction in the antinociceptive effect and associated downregulation of the GTs. We conclude that NMDA receptor suppression inhibits EAA excitation and reduces the morphine-induced antinociception in PTX-treated rats.

Original languageEnglish
Pages (from-to)69-74
Number of pages6
JournalBrain Research Bulletin
Volume80
Issue number1-2
DOIs
Publication statusPublished - Aug 28 2009
Externally publishedYes

Fingerprint

Amino Acid Transport System X-AG
Excitatory Amino Acids
Pertussis Toxin
Morphine
Cerebrospinal Fluid
Spinal Cord
Down-Regulation
Dialysis Solutions
Hyperalgesia
Microdialysis
Catheters
2-Amino-5-phosphonovalerate
Injections
Analgesics
aspartic acid receptor
Wistar Rats
Protein Isoforms
High Pressure Liquid Chromatography

Keywords

  • Glutamate transporters
  • Morphine
  • NMDA receptors
  • Pertussis toxin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

N-Methyl-d-aspartate receptor antagonist d-AP5 prevents pertussis toxin-induced alterations in rat spinal cords by inhibiting increase in concentrations of spinal CSF excitatory amino acids and downregulation of glutamate transporters. / Wong, Chih Shung; Wu, Gong-Jhe; Chen, Wu Fu; Jean, Yen Hsuan; Hung, Ching Hsien; Lin, Chan Shing; Huang, Shi Ying; Wen, Zhi Hong.

In: Brain Research Bulletin, Vol. 80, No. 1-2, 28.08.2009, p. 69-74.

Research output: Contribution to journalArticle

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AU - Chen, Wu Fu

AU - Jean, Yen Hsuan

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AU - Wen, Zhi Hong

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