Pulsed Radiofrequency Upregulates Serotonin Transporters and Alleviates Neuropathic Pain-Induced Depression in a Spared Nerve Injury Rat Model

Neuropathic pain (NP) is difficult to treat due to complex pathophysiological mechanisms. Pulsed radiofrequency (RRF) has been used widely with neuromodulation effect in refractory chronic pain treatment. A recent study found that PRF treatment may decrease chronic pain-related anxiety-depressant sy...

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Main Authors: Kuo-Hsing Ma, Cheng-Yi Cheng, Wei-Hung Chan, Shih-Yu Chen, Li-Ting Kao, Chun-Sung Sung, Dueng-Yuan Hueng, Chun-Chang Yeh
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/9/10/1489
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author Kuo-Hsing Ma
Cheng-Yi Cheng
Wei-Hung Chan
Shih-Yu Chen
Li-Ting Kao
Chun-Sung Sung
Dueng-Yuan Hueng
Chun-Chang Yeh
author_facet Kuo-Hsing Ma
Cheng-Yi Cheng
Wei-Hung Chan
Shih-Yu Chen
Li-Ting Kao
Chun-Sung Sung
Dueng-Yuan Hueng
Chun-Chang Yeh
author_sort Kuo-Hsing Ma
collection DOAJ
description Neuropathic pain (NP) is difficult to treat due to complex pathophysiological mechanisms. Pulsed radiofrequency (RRF) has been used widely with neuromodulation effect in refractory chronic pain treatment. A recent study found that PRF treatment may decrease chronic pain-related anxiety-depressant symptoms in patients, even though the mechanisms are unclear. Additionally, accumulated evidence has shown serotonin uptake is correlated with various neuropsychiatric diseases. Therefore, we investigated the effects and underlying mechanisms of PRF on depression-like behaviors, resulting from spared nerve injury (SNI)-induced NP. We examined the indexes of mechanical allodynia, cold allodynia, depression-like behavior, and blood cytokines by dynamic plantar aesthesiometry, acetone spray test, forced swimming test, and ProcartaPlex multiplex immunoassays in male Wistar rats, respectively. Serotonin transporters (SERTs) in rat brains were examined by using 4-[18F]-ADAM/PET imaging. We found that specific uptake ratios (SURs) of SERTs were significantly decreased in the brain regions of the thalamus and striatum in rats with SNI-induced NP and depression-like behaviors. Additionally, the decrease in SERT density was correlated with the development of a depression-like behavior indicated by the forced swimming test results and pronounced IL-6 cytokines. Moreover, we demonstrated that PRF application could modulate the descending serotoninergic pathway to relieve pain and depression behaviors.
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spelling doaj.art-37a34b77efed4e0eb7a48648efe8f44d2023-11-22T17:32:43ZengMDPI AGBiomedicines2227-90592021-10-01910148910.3390/biomedicines9101489Pulsed Radiofrequency Upregulates Serotonin Transporters and Alleviates Neuropathic Pain-Induced Depression in a Spared Nerve Injury Rat ModelKuo-Hsing Ma0Cheng-Yi Cheng1Wei-Hung Chan2Shih-Yu Chen3Li-Ting Kao4Chun-Sung Sung5Dueng-Yuan Hueng6Chun-Chang Yeh7Department of Biology and Anatomy, National Defense Medical Center, Taipei 115, TaiwanDepartment of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 115, TaiwanDepartment of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei 115, TaiwanDepartment of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei 115, TaiwanDepartment of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei 115, TaiwanDepartment of Anesthesiology, Taipei Veterans General Hospital, Taipei 112, TaiwanDepartment of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 115, TaiwanDepartment of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei 115, TaiwanNeuropathic pain (NP) is difficult to treat due to complex pathophysiological mechanisms. Pulsed radiofrequency (RRF) has been used widely with neuromodulation effect in refractory chronic pain treatment. A recent study found that PRF treatment may decrease chronic pain-related anxiety-depressant symptoms in patients, even though the mechanisms are unclear. Additionally, accumulated evidence has shown serotonin uptake is correlated with various neuropsychiatric diseases. Therefore, we investigated the effects and underlying mechanisms of PRF on depression-like behaviors, resulting from spared nerve injury (SNI)-induced NP. We examined the indexes of mechanical allodynia, cold allodynia, depression-like behavior, and blood cytokines by dynamic plantar aesthesiometry, acetone spray test, forced swimming test, and ProcartaPlex multiplex immunoassays in male Wistar rats, respectively. Serotonin transporters (SERTs) in rat brains were examined by using 4-[18F]-ADAM/PET imaging. We found that specific uptake ratios (SURs) of SERTs were significantly decreased in the brain regions of the thalamus and striatum in rats with SNI-induced NP and depression-like behaviors. Additionally, the decrease in SERT density was correlated with the development of a depression-like behavior indicated by the forced swimming test results and pronounced IL-6 cytokines. Moreover, we demonstrated that PRF application could modulate the descending serotoninergic pathway to relieve pain and depression behaviors.https://www.mdpi.com/2227-9059/9/10/1489pulsed radiofrequencyneuropathic paindepression-like behaviorspositron emission tomographyserotonin transporters
spellingShingle Kuo-Hsing Ma
Cheng-Yi Cheng
Wei-Hung Chan
Shih-Yu Chen
Li-Ting Kao
Chun-Sung Sung
Dueng-Yuan Hueng
Chun-Chang Yeh
Pulsed Radiofrequency Upregulates Serotonin Transporters and Alleviates Neuropathic Pain-Induced Depression in a Spared Nerve Injury Rat Model
Biomedicines
pulsed radiofrequency
neuropathic pain
depression-like behaviors
positron emission tomography
serotonin transporters
title Pulsed Radiofrequency Upregulates Serotonin Transporters and Alleviates Neuropathic Pain-Induced Depression in a Spared Nerve Injury Rat Model
title_full Pulsed Radiofrequency Upregulates Serotonin Transporters and Alleviates Neuropathic Pain-Induced Depression in a Spared Nerve Injury Rat Model
title_fullStr Pulsed Radiofrequency Upregulates Serotonin Transporters and Alleviates Neuropathic Pain-Induced Depression in a Spared Nerve Injury Rat Model
title_full_unstemmed Pulsed Radiofrequency Upregulates Serotonin Transporters and Alleviates Neuropathic Pain-Induced Depression in a Spared Nerve Injury Rat Model
title_short Pulsed Radiofrequency Upregulates Serotonin Transporters and Alleviates Neuropathic Pain-Induced Depression in a Spared Nerve Injury Rat Model
title_sort pulsed radiofrequency upregulates serotonin transporters and alleviates neuropathic pain induced depression in a spared nerve injury rat model
topic pulsed radiofrequency
neuropathic pain
depression-like behaviors
positron emission tomography
serotonin transporters
url https://www.mdpi.com/2227-9059/9/10/1489
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