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

Title
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
Author(s)
송선옥노대현[노대현]서홍식[서홍식]윤서연[윤서연]한호재[한호재]Alvin J. Beitz[Alvin J. Beitz]이장헌[이장헌]
Keywords
PERIPHERAL-NERVE INJURY; DORSAL-HORN NEURONS; NMDA RECEPTOR; NEUROPATHIC PAIN; MECHANICAL ALLODYNIA; SUBSTANCE-P; CORD; CLONIDINE; ANALGESIA; CAPSAICIN
Issue Date
201002
Publisher
LIPPINCOTT WILLIAMS & WILKINS
Citation
ANESTHESIA AND ANALGESIA, v.110, no.2, pp.622 - 629
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 mu g/rat) or DAMGO (1 mu g/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 mu g/rat) or an alpha-2C (JP-1302, 50 mu g/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. (Anesth Anal 20 10; 110:622-9)
URI
http://hdl.handle.net/YU.REPOSITORY/22919http://dx.doi.org/10.1213/ANE.0b013e3181c8afc1
ISSN
0003-2999
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의과대학 > 마취통증의학교실 > Articles
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