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Intrathecal Clonidine Suppresses Phosphorylation of the N-Methyl-D-Aspartate Receptor NR1 Subunit in Spinal Dorsal Horn Neurons of Rats with Neuropathic Pain

Cited 39 time in Web of Science Cited 41 time in Scopus
Authors
Roh, Dae-Hyun; Kim, Hyun-Woo; Yoon, Seo Yeon; Seo, Hyoung-Sig; Kwon, Young-Bae; Han, Ho-Jae; Beitz, Alvin J.; Lee, Jang-Hern
Issue Date
2008
Publisher
Lippincott, Williams & Wilkins
Citation
Anesth Analg 2008;107:693-700
Abstract
BACKGROUND: Intrathecal (IT) administration of the -2 adrenoceptor agonist, clonidine, produces significant analgesic effects. Although several mechanisms underlying clonidine-induced analgesia have been proposed, the possible interaction with N-methyl-D-aspartate (NMDA) receptors as a major antinociceptive mechanism has not been addressed. We designed the present study to determine whether clonidine or other analgesics can affect spinal NMDA receptor activation in rats with chronic constriction injury (CCI)-induced neuropathy.

METHODS: Rats underwent unilateral CCI, and received IT clonidine (1, 5, 20 µg/rat), [d-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO, µ opioid receptor agonist, 1 µg/rat), gabapentin (anticonvulsant, 100 µg/rat) or vehicle 2 wks later. After drug injection, we measured the pain response to thermal or mechanical stimuli and used immunohistochemistry to evaluate spinal cord phosphorylated NMDA-receptor subunit 1 (pNR1) expression.

RESULTS: Two weeks after CCI surgery, rats displayed significant mechanical allodynia and thermal hyperalgesia, and the spinal cord dorsal horn showed a significant increase in the number of pNR1 immunoreactive neurons. IT injection of clonidine (20 µg/rat), DAMGO and gabapentin potently reduced mechanical allodynia and thermal hyperalgesia. Importantly, IT clonidine, but not IT DAMGO or gabapentin, dose-dependently reduced CCI-induced pNR1 expression in all lamina of the spinal cord dorsal horn by 30 min after injection. In addition, IT injection of the -2 adrenoceptor antagonist, idazoxan (40 µg/rat) 10 min before clonidine injection completely reversed clonidine’s antihyperalgesic and antiallodynic effects, as well as clonidine’s suppressive effect on CCI-induced NR1 phosphorylation in the spinal cord dorsal horn.

CONCLUSIONS: Our data indicate that IT clonidine’s antihyperalgesic/antiallodynic effect on neuropathic pain is associated with a significant reduction in spinal NMDA receptor phosphorylation and suggests a potentially novel mechanism of clonidine’s action.
ISSN
0003-2999
Language
English
URI
http://hdl.handle.net/10371/8290
DOI
https://doi.org/10.1213/ane.0b013e31817e7319
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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