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Activation of spinal alpha-2 adrenoceptors, but not mu-opioid receptors, reduces the intrathecal N-methyl-D-aspartate-induced increase in spinal NR1 subunit phosphorylation and nociceptive behaviors in the rat.
Anesth Analg. 2010 Feb 01; 110(2):622-9.A&A

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 alpha-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 mu-opioid receptor agonist, [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO).

METHODS

We examined the effect of clonidine (20 microg/rat) or DAMGO (1 microg/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 alpha-2A or alpha-2C adrenoceptors. Finally, rat spinal cords were immunohistochemically processed for double staining of pNR1 and alpha-2A or alpha-2C adrenoceptors or mu-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 alpha-2A (BRL44408, 30 microg/rat) or an alpha-2C (JP-1302, 50 microg/rat) adrenoceptor antagonist. In addition, immunocytochemistry revealed that spinal pNR1 immunoreactive cells co-contain alpha-2A and alpha-2C adrenoceptors.

CONCLUSIONS

These results demonstrate that the IT NMDA-induced increase in pNR1 expression and nociceptive behavior is significantly reduced by activation of alpha-2 adrenoceptors, but not mu-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.

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Authors+Show Affiliations

Roh DH
Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea.
Seo HS
No affiliation info available
Yoon SY
No affiliation info available
Song S
No affiliation info available
Han HJ
No affiliation info available
Beitz AJ
No affiliation info available
Lee JH
No affiliation info available

MeSH

Adrenergic alpha-2 Receptor AntagonistsAdrenergic alpha-AgonistsAnalgesicsAnimalsBehavior, AnimalClonidineEnkephalin, Ala(2)-MePhe(4)-Gly(5)-ImmunohistochemistryInjections, SpinalMaleN-MethylaspartatePainPhosphorylationPosterior Horn CellsRatsRats, Sprague-DawleyReceptors, Adrenergic, alpha-2Receptors, N-Methyl-D-AspartateReceptors, Opioid, mu

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20007733

Citation

Roh, Dae-Hyun, et al. "Activation of Spinal Alpha-2 Adrenoceptors, but Not Mu-opioid Receptors, Reduces the Intrathecal N-methyl-D-aspartate-induced Increase in Spinal NR1 Subunit Phosphorylation and Nociceptive Behaviors in the Rat." Anesthesia and Analgesia, vol. 110, no. 2, 2010, pp. 622-9.
Roh DH, Seo HS, Yoon SY, et al. Activation of spinal alpha-2 adrenoceptors, but not mu-opioid receptors, reduces the intrathecal N-methyl-D-aspartate-induced increase in spinal NR1 subunit phosphorylation and nociceptive behaviors in the rat. Anesth Analg. 2010;110(2):622-9.
Roh, D. H., Seo, H. S., Yoon, S. Y., Song, S., Han, H. J., Beitz, A. J., & Lee, J. H. (2010). Activation of spinal alpha-2 adrenoceptors, but not mu-opioid receptors, reduces the intrathecal N-methyl-D-aspartate-induced increase in spinal NR1 subunit phosphorylation and nociceptive behaviors in the rat. Anesthesia and Analgesia, 110(2), 622-9. https://doi.org/10.1213/ANE.0b013e3181c8afc1
Roh DH, et al. Activation of Spinal Alpha-2 Adrenoceptors, but Not Mu-opioid Receptors, Reduces the Intrathecal N-methyl-D-aspartate-induced Increase in Spinal NR1 Subunit Phosphorylation and Nociceptive Behaviors in the Rat. Anesth Analg. 2010 Feb 1;110(2):622-9. PubMed PMID: 20007733.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of spinal alpha-2 adrenoceptors, but not mu-opioid receptors, reduces the intrathecal N-methyl-D-aspartate-induced increase in spinal NR1 subunit phosphorylation and nociceptive behaviors in the rat. AU - Roh,Dae-Hyun, AU - Seo,Hyoung-Sig, AU - Yoon,Seo-Yeon, AU - Song,Sunok, AU - Han,Ho-Jae, AU - Beitz,Alvin J, AU - Lee,Jang-Hern, Y1 - 2009/12/10/ PY - 2009/12/17/entrez PY - 2009/12/17/pubmed PY - 2010/2/9/medline SP - 622 EP - 9 JF - Anesthesia and analgesia JO - Anesth Analg VL - 110 IS - 2 N2 - 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 alpha-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 mu-opioid receptor agonist, [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO). METHODS: We examined the effect of clonidine (20 microg/rat) or DAMGO (1 microg/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 alpha-2A or alpha-2C adrenoceptors. Finally, rat spinal cords were immunohistochemically processed for double staining of pNR1 and alpha-2A or alpha-2C adrenoceptors or mu-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 alpha-2A (BRL44408, 30 microg/rat) or an alpha-2C (JP-1302, 50 microg/rat) adrenoceptor antagonist. In addition, immunocytochemistry revealed that spinal pNR1 immunoreactive cells co-contain alpha-2A and alpha-2C adrenoceptors. CONCLUSIONS: These results demonstrate that the IT NMDA-induced increase in pNR1 expression and nociceptive behavior is significantly reduced by activation of alpha-2 adrenoceptors, but not mu-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. SN - 1526-7598 UR - https://www.unboundmedicine.com/medline/citation/20007733/Activation_of_spinal_alpha_2_adrenoceptors_but_not_mu_opioid_receptors_reduces_the_intrathecal_N_methyl_D_aspartate_induced_increase_in_spinal_NR1_subunit_phosphorylation_and_nociceptive_behaviors_in_the_rat_ L2 - https://doi.org/10.1213/ANE.0b013e3181c8afc1 DB - PRIME DP - Unbound Medicine ER -