Strategies to Treat Chronic Pain and Strengthen Impaired Descending Noradrenergic Inhibitory System
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...
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doaj-35670306019b4d049d464fff9a1132a42020-11-25T02:00:08ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-02-0120482210.3390/ijms20040822ijms20040822Strategies to Treat Chronic Pain and Strengthen Impaired Descending Noradrenergic Inhibitory SystemKen-ichiro Hayashida0Hideaki Obata1Doctorial Course in Medicine, Organ Function-Oriented Medicine, Akita University Graduate School of Medicine;1-1-1, Hondo, Akita-City, Akita 010-8543, JapanCenter for Pain Management and Department of Anesthesiology, Fukushima Medical University; 1 Hikarigaoka, Fukushima-City, Fukushima 960-1295, JapanGabapentinoids (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 α<sub>2</sub>-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.https://www.mdpi.com/1422-0067/20/4/822locus coeruleusnoradrenalinedescending inhibitionspinal cordα<sub>2</sub>-adrenergic receptorsneuropathic painhypersensitivityrats |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ken-ichiro Hayashida Hideaki Obata |
spellingShingle |
Ken-ichiro Hayashida Hideaki Obata Strategies to Treat Chronic Pain and Strengthen Impaired Descending Noradrenergic Inhibitory System International Journal of Molecular Sciences locus coeruleus noradrenaline descending inhibition spinal cord α<sub>2</sub>-adrenergic receptors neuropathic pain hypersensitivity rats |
author_facet |
Ken-ichiro Hayashida Hideaki Obata |
author_sort |
Ken-ichiro Hayashida |
title |
Strategies to Treat Chronic Pain and Strengthen Impaired Descending Noradrenergic Inhibitory System |
title_short |
Strategies to Treat Chronic Pain and Strengthen Impaired Descending Noradrenergic Inhibitory System |
title_full |
Strategies to Treat Chronic Pain and Strengthen Impaired Descending Noradrenergic Inhibitory System |
title_fullStr |
Strategies to Treat Chronic Pain and Strengthen Impaired Descending Noradrenergic Inhibitory System |
title_full_unstemmed |
Strategies to Treat Chronic Pain and Strengthen Impaired Descending Noradrenergic Inhibitory System |
title_sort |
strategies to treat chronic pain and strengthen impaired descending noradrenergic inhibitory system |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-02-01 |
description |
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 α<sub>2</sub>-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. |
topic |
locus coeruleus noradrenaline descending inhibition spinal cord α<sub>2</sub>-adrenergic receptors neuropathic pain hypersensitivity rats |
url |
https://www.mdpi.com/1422-0067/20/4/822 |
work_keys_str_mv |
AT kenichirohayashida strategiestotreatchronicpainandstrengthenimpaireddescendingnoradrenergicinhibitorysystem AT hideakiobata strategiestotreatchronicpainandstrengthenimpaireddescendingnoradrenergicinhibitorysystem |
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