ReferenceID 5106

The Anxiolytic and Antidepressant Effects of Diallyl Disulfide and GYY4137 in Animals with Chronic Neuropathic Pain

Antioxidants (Basel)

When neuropathic pain is maintained long term, it can also lead to the development of emotional disorders that are even more intense than pain perception and difficult to treat. Hydrogen sulfide (H2S) donors relieve chro

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Reference Id
5106
Evidence Id
21696
Core Evidence Id
21696
Source Reference Id
3502
Herb2 Reference Id
HBREF004299
Subject Paper Key
HBIN023556_34356307
Pubmed Id
34356307
Doi
10.3390/antiox10071074
Paper Title
The Anxiolytic and Antidepressant Effects of Diallyl Disulfide and GYY4137 in Animals with Chronic Neuropathic Pain
Paper Abstract
When neuropathic pain is maintained long term, it can also lead to the development of emotional disorders that are even more intense than pain perception and difficult to treat. Hydrogen sulfide (H2S) donors relieve chronic pain, but their effects on the associated mood disorders are not completely elucidated. We evaluated if treatment with DADS (diallyl disulfide) or GYY4137 (morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex), two slow-releasing H2S donors, inhibits the anxiety- and depressive-like behaviors that concur with chronic neuropathic pain generated by sciatic nerve injury in mice. The modulatory role of these drugs in the inflammatory, apoptotic, and oxidative processes implicated in the development of the affective disorders was assessed. Our results revealed the anxiolytic, antidepressant, and antinociceptive properties of DADS and GYY4137 during neuropathic pain by inhibiting microglial activation and the up-regulation of phosphoinositide 3-kinase/phosphorylated protein kinase B and BAX in the amygdala (AMG) and/or periaqueductal gray matter (PAG). Both treatments also normalized and/or activated the endogenous antioxidant system, but only DADS blocked ERK 1/2 phosphorylation. Both H2S donors decreased allodynia and hyperalgesia in a dose-dependent manner by activating the Kv7 potassium channels and heme oxygenase 1 signaling pathways. This study provides evidence of the anxiolytic and antidepressant properties of DADS and GYY4137 during neuropathic pain and reveals their analgesic actions, suggesting that these therapeutic properties may result from the inhibition of the inflammatory, apoptotic, and oxidative responses in the AMG and/or PAG. These findings support the use of these treatments for the management of affective disorders accompanying chronic neuropathic pain.
Journal
Antioxidants (Basel)
Publish Year
2021
Experiment Subject
mouse
Experiment Type
Animal Experiment
Phenotype Related
Affective Disorders; Chronic Neuropathic Pain; Sciatic Nerve Injury; Mood Disorders; Emotional Disorders; Chronic Pain; Neuropathic Pain
Paper Title Cn
Paper Title En
The Anxiolytic and Antidepressant Effects of Diallyl Disulfide and GYY4137 in Animals with Chronic Neuropathic Pain
Bilingual Status
semi_complete