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Int. J. Mol. Sci. 2019, 20(4), 822; https://doi.org/10.3390/ijms20040822

Strategies to Treat Chronic Pain and Strengthen Impaired Descending Noradrenergic Inhibitory System

1
Doctorial Course in Medicine, Organ Function-Oriented Medicine, Akita University Graduate School of Medicine;1-1-1, Hondo, Akita-City, Akita 010-8543, Japan
2
Center for Pain Management and Department of Anesthesiology, Fukushima Medical University; 1 Hikarigaoka, Fukushima-City, Fukushima 960-1295, Japan
*
Author to whom correspondence should be addressed.
Received: 12 January 2019 / Revised: 4 February 2019 / Accepted: 12 February 2019 / Published: 14 February 2019
(This article belongs to the Special Issue Neuroprotective Strategies 2018)
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Abstract

Gabapentinoids (gabapentin and pregabalin) and antidepressants (tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors) are often used to treat chronic pain. The descending noradrenergic inhibitory system from the locus coeruleus (LC) to the dorsal horn of the spinal cord plays an important role in the analgesic mechanisms of these drugs. Gabapentinoids activate the LC by inhibiting the release of γ-aminobutyric acid (GABA) and inducing the release of glutamate, thereby increasing noradrenaline levels in the spinal cord. Antidepressants increase noradrenaline levels in the spinal cord by inhibiting reuptake, and accumulating noradrenaline inhibits chronic pain through α2-adrenergic receptors in the spinal cord. Recent animal studies, however, revealed that the function of the descending noradrenergic inhibitory system is impaired in chronic pain states. Other recent studies found that histone deacetylase inhibitors and antidepressants restore the impaired noradrenergic descending inhibitory system acting on noradrenergic neurons in the LC. View Full-Text
Keywords: locus coeruleus; noradrenaline; descending inhibition; spinal cord; α2-adrenergic receptors; neuropathic pain; hypersensitivity; rats locus coeruleus; noradrenaline; descending inhibition; spinal cord; α2-adrenergic receptors; neuropathic pain; hypersensitivity; rats
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Hayashida, K.-I.; Obata, H. Strategies to Treat Chronic Pain and Strengthen Impaired Descending Noradrenergic Inhibitory System. Int. J. Mol. Sci. 2019, 20, 822.

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