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Curcumin Improves Chronic Pain Induced Depression Through Regulating Serum Metabolomics in a Rat Model of Trigeminal Neuralgia

Authors Zhang L, Ma Z, Wu Z, Jin M, An L, Xue F

Received 27 September 2020

Accepted for publication 12 December 2020

Published 29 December 2020 Volume 2020:13 Pages 3479—3492


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Michael Schatman

Li Zhang,1,* Zhijie Ma,2 Zhe Wu,3 Mu Jin,1 Lixin An,1 Fushan Xue1,*

1Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, People’s Republic of China; 2Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University, Beijing 100012, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Li Zhang; Fushan Xue
Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong’an Road, Xicheng District, Beijing 100050, People’s Republic of China
Email [email protected]; [email protected]

Background: Depression is a prevalent and complex psychiatric disorder with high incidence in patients with chronic pain. The underlying pathogenesis of chronic pain-induced depression is complicated and remains largely unclear. An integrated analysis of endogenous substance-related metabolisms would help to understand the molecular mechanism of chronic pain-induced depression. Curcumin was reported to exert various health benefits, such as anti-depression, antioxidant, antineoplastic, analgesia, and anti-inflammation.
Objective: The aim of this study was to analyze the biomarkers related to depression in serum and to evaluate the anti-depression properties of curcumin in a chronic pain-induced depression model of rats.
Design: This is a randomized, controlled experiment.
Setting: This study was conducted at the Experimental Animal Center, Beijing Friendship Hospital, Capital Medical University.
Methods: Trigeminal neuralgia (TN) was produced by injecting 4 μL, 10% cobra venom saline solution into the infraorbital nerve (ION). Curcumin was administered by gavage twice a day from post-operation day (POD) 15 to POD 42. Mechanical allodynia was assessed using von Frey filaments. Sucrose preference and forced swimming tests were performed to evaluate depression-like behaviors. The metabolomics analysis was preceded by LCMS-IT-TOF and multivariate statistical methods for sample detection and biomarker screening.
Results: Cobra venom intra-ION injection led to chronic mechanical allodynia, reduced sucrose preference, and prolonged immobility during forced swimming. Curcumin treatment alleviated chronic mechanical allodynia, regained sucrose preference, and reduced immobility time. Differential analysis identified 30 potential metabolites changed under TN condition. The integrated analyses further revealed two major metabolic changes by comparing the serums from sham operated rats, TN rats, and TN rats treated with curcumin: 1) ether lipid metabolism; and 2) glycerophospholipid metabolism, and suggested that curcumin may improve chronic pain-induced depression by regulating these two types of lipid metabolisms.
Conclusion: Ether lipid and glycerophospholipid metabolism might be two of the pathways with the most potential related to chronic pain induced-depression; and curcumin could alleviate chronic pain induced-depression by modulating these two pathways. These results provide further insights into the mechanisms of chronic pain-induced depression and may help to identify potential targets for anti-depression properties of curcumin.

Keywords: curcumin, depression, chronic pain, trigeminal neuralgia, metabolomics

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