The Roles of Excitatory Amino Acids and Cytokines in Morphine Tolerance: Effect of Tricyclic Antidepressant Amitriptylin
Yueh-Hua Tai1, Wen-Jinn Liaw 1, Yuan-Xiang Tao2, Chih-Shung Wong*, 1
Identifiers and Pagination:Year: 2009
First Page: 64
Last Page: 70
Publisher Id: TOPAINJ-2-64
Article History:Received Date: 23/04/2009
Revision Received Date: 22/06/2009
Acceptance Date: 29/07/2009
Electronic publication date: 15/10/2009
Collection year: 2009
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Morphine is an effective analgesic in clinical practice; however, its long-term administration causes tolerance, thereby limiting its use. The development of opioid tolerance and its associated hyperalgesia has been associated with interactions between opioid receptors and excitatory amino acids or cytokines. Targeted inhibition of excitatory amino acid- and cytokine-mediated signaling pathways may allow development of novel therapeutic strategies for treating opioid tolerance. Recent studies showed that administration of amitriptyline (a tricyclic antidepressant widely used in the treatment of neuropathic pain) attenuated morphine tolerance and preserved the antinociceptive effect of morphine. This ability might be related to the effects of tricyclic antidepressants on pro-inflammatory cytokine release and glutamate transporter expression in dorsal horn during morphine tolerance. Here, we will review evidence for the role of excitatory amino acids and cytokines in the development of morphine tolerance and discuss potential mechanisms by which tricyclic antidepressants attenuate morphine tolerance.