Activation of spinal α-2 adrenoceptors, but not μ-opioid receptors, reduces the intrathecal n-methyl-d-aspartate-induced increase in spinal nr1 subunit phosphorylation and nociceptive behaviors in the rat

Dae Hyun Roh, Hyoung Sig Seo, Seo Yeon Yoon, Sunok Song, Ho Jae Han, Alvin J. Beitz, Jang Hern Lee

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background: A previous study from our laboratories showed that a significant reduction in spinal N-methyl-d-aspartate (NMDA) receptor NR1 subunit phosphorylation (pNR1) is associated with the antiallodynic effect produced by intrathecal (IT) injection of the α-2 adrenoceptor agonist, clonidine, in neuropathic rats. In this study, we determined whether the spontaneous pain and increased pNR1 expression induced by NMDA injection are reduced by IT injection of either clonidine or the μ-opioid receptor agonist, [d-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO). Methods: We examined the effect of clonidine (20 μg/rat) or DAMGO (1 μg/rat) injection on IT NMDA-induced spontaneous nociceptive behavior and pNR1 expression in the spinal dorsal horn. We also determined whether the effect of clonidine is mediated by α-2A or α-2C adrenoceptors. Finally, rat spinal cords were immunohistochemically processed for double staining of pNR1 and α-2A or α-2C adrenoceptors or μ-opioid receptors. Results: The NMDA-induced increase in both pNR1 expression and nociceptive behavior was significantly reduced by IT clonidine but not DAMGO. This analgesic effect of clonidine was blocked by administration of either an α-2A (BRL44408, 30 μg/rat) or an α-2C (JP-1302, 50 μg/rat) adrenoceptor antagonist. In addition, immunocytochemistry revealed that spinal pNR1 immunoreactive cells co-contain α-2A and α-2C adrenoceptors. Conclusions: These results demonstrate that the IT NMDA-induced increase in pNR1 expression and nociceptive behavior is significantly reduced by activation of α-2 adrenoceptors, but not μ-opioid receptors, in the spinal cord dorsal horn. Furthermore, these findings suggest that the modulation of spinal NR1 phosphorylation is linked to the effect of IT clonidine on postsynaptic neuronal activity.

Original languageEnglish (US)
Pages (from-to)622-629
Number of pages8
JournalAnesthesia and analgesia
Volume110
Issue number2
DOIs
StatePublished - Feb 2010

Fingerprint Dive into the research topics of 'Activation of spinal α-2 adrenoceptors, but not μ-opioid receptors, reduces the intrathecal n-methyl-d-aspartate-induced increase in spinal nr1 subunit phosphorylation and nociceptive behaviors in the rat'. Together they form a unique fingerprint.

Cite this