Dataset Information

Pain Relief Dependent on IL-17-CD4⁺ T Cell-?-Endorphin Axis in Rat Model of Brachial Plexus Root Avulsion After Electroacupuncture Therapy.

ABSTRACT:

Background and purpose

Neuropathic pain is the typical symptom of brachial plexus root avulsion (BPRA), and no effective therapy is currently available. Electroacupuncture (EA), as a complementary and alternative therapy, plays a critical role in the management of pain-associated diseases. In the present study, we aimed to reveal the peripheral immunological mechanism of EA in relieving the pain of BPRA through the IL-17-CD4⁺ T lymphocyte-?-endorphin axis.

Methods

After receiving repeated EA treatment, the pain of BPRA in rats along with the expressions of a range of neurotransmitters, the contents of inflammatory cytokines, and the population of lymphocytes associated were investigated. CD4⁺ T lymphocytes were either isolated or depleted with anti-CD4 monoclonal antibody. The titers of IL-17A, interferon-? (IFN-?), and ?-endorphin were examined. The markers of T lymphocytes, myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), macrophages, and natural killer (NK) cells were assessed. The activation of the nuclear transcription factor ?B (NF-?B) signaling pathway was tested.

Results

The pain of BPRA was significantly relieved, and the amount of CD4⁺ T lymphocytes was increased after EA treatment. The release of ?-endorphin was up-regulated with the up-regulation of IL-17A in CD4⁺ T lymphocytes. The titer of IL-17A was enhanced, leading to an activated NF-?B signaling pathway. The release of ?-endorphin and the analgesic effect were almost completely abolished when CD4⁺ T lymphocytes were depleted.

Conclusion

We, for the first time, showed that the neuropathic pain caused by BPRA was effectively relieved by EA treatment via IL-17-CD4⁺ T lymphocyte-?-endorphin mediated peripheral analgesic effect, providing scientific support for EA clinical application.

SUBMITTER: Xu Z

PROVIDER: S-EPMC7901907 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Pain Relief Dependent on IL-17-CD4<sup>+</sup> T Cell-β-Endorphin Axis in Rat Model of Brachial Plexus Root Avulsion After Electroacupuncture Therapy.

Xu Zihang Z Zhu Yangzhuangzhuang Y Shen Jun J Su Lin L Hou Yifei Y Liu Mingxi M Jiao Xiaoning X Chen Xiao X Zhu Shiguo S Lu Yechen Y Yao Chao C Wang Lixin L Gong Chenyuan C Ma Zhenzhen Z Zou Chunpu C Xu Jianguang J

Frontiers in neuroscience 20210209

<h4>Background and purpose</h4>Neuropathic pain is the typical symptom of brachial plexus root avulsion (BPRA), and no effective therapy is currently available. Electroacupuncture (EA), as a complementary and alternative therapy, plays a critical role in the management of pain-associated diseases. In the present study, we aimed to reveal the peripheral immunological mechanism of EA in relieving the pain of BPRA through the IL-17-CD4<sup>+</sup> T lymphocyte-β-endorphin axis.<h4>Methods</h4>After ...[more]

PMID: 33633527

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Project description:Objective: The present study aimed to investigate the analgesic effect of electroacupuncture (EA) in neuropathic pain due to brachial plexus avulsion injury (BPAI) and related changes in the metabolic brain connectivity. Methods: Neuropathic pain model due to BPAI was established in adult female Sprague-Dawley rats. EA stimulations (2/15 Hz, 30 min/day, 5-day intervention followed by 2-day rest in each session) were applied to the fifth-seventh cervical "Jiaji" acupoints on the noninjured side from 1st to 12th weeks following BPAI (EA group, n = 8). Three control groups included sham EA (nonelectrical acupuncture applied to 3 mm lateral to the real "Jiaji" acupoints), BPAI-only, and normal rats (no particular intervention; eight rats in each group). Thermal withdrawal latency (TWL) of the noninjured forepaw was regularly tested to evaluate the threshold of thermalgesia. Small animal [fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT scans of brain were conducted at the end of 4th, 12th, and 16th weeks to explore metabolic alterations of brain. Results: In the EA group, the TWL of the noninjured forepaw significantly decreased following BPAI and then increased following EA stimulation, compared with sham EA (P < 0.001). The metabolic brain connectivity among somatosensory cortex (SC), motor cortex (MC), caudate putamen (Cpu), and dorsolateral thalamus (DLT) in bilateral hemispheres decreased throughout the 16 weeks' observation in the BPAI-only group, compared with the normal rats (P < 0.05). In the EA group, the strength of connectivity among the above regions were found to be increased at the end of 4th week following BPAI modeling, decreased at 12th week, and then increased again at 16th week (P < 0.05). The changes in metabolic connectivity were uncharacteristic and dispersed in the sham EA group. Conclusion: The study revealed long-term and extensive changes of metabolic brain connectivity in EA-treated BPAI-induced neuropathic pain rats. Bilateral sensorimotor and pain-related brain regions were mainly involved in this process. It indicated that modulation of brain metabolic connectivity might be an important mechanism of analgesic effect in EA stimulation for the treatment of neuropathic pain.

Project description:BackgroundSpinal root avulsion induces multiple pathophysiological events consisting of altered levels of specific genes and proteins related to inflammation, apoptosis, and oxidative stress, which collectively result in the death of the affected motoneurons. Recent studies have demonstrated that the gene changes involved in spinal cord injury can be regulated by microRNAs, which are a class of short non-coding RNA molecules that repress target mRNAs post-transcriptionally. With consideration for the time course of the avulsion-induced gene expression patterns within dying motoneurons, we employed microarray analysis to determine whether and how microRNAs are involved in the changes of gene expression induced by pathophysiological events in spinal cord motoneurons.ResultsThe expression of a total of 3,361 miRNAs in the spinal cord of adult rats was identified. Unilateral root-avulsion resulted in significant alterations in miRNA expression. In the ipsilateral half compared to the contralateral half of the spinal cord, on the 3rd day after the injury, 55 miRNAs were upregulated, and 24 were downregulated, and on the 14th day after the injury, 36 miRNAs were upregulated, and 23 were downregulated. The upregulation of miR-146b-5p and miR-31a-3p and the downregulation of miR-324-3p and miR-484 were observed. Eleven of the miRNAs, including miR-21-5p, demonstrated a sustained increase; however, only miR-466c-3p presented a sustained decrease 3 and 14 days after the injury. More interestingly, 4 of the miRNAs, including miR-18a, were upregulated on the 3rd day but were downregulated on the 14th day after injury.Some of these miRNAs target inflammatory-response genes in the early stage of injury, and others target neurotransmitter transport genes in the intermediate stages of injury. The altered miRNA expression pattern suggests that the MAPK and calcium signaling pathways are consistently involved in the injury response.ConclusionsThis analysis may facilitate the understanding of the time-specific altered expression of a large set of microRNAs in the spinal cord after brachial root avulsion.

Project description:Background and purposeBrachial plexus birth injury is caused by traction on the neck during delivery and results in flaccid palsy of an upper extremity commonly involving C5-C6 nerve roots. MR imaging and MR myelography help to assess the anatomic location, extent, and severity of brachial plexus injuries which influence the long-term prognosis along with the surgical decision making. Recently, sonography has been increasingly used as the imaging modality of choice for brachial plexus injuries. The aim of this study was to assess the degree of correlation among brachial plexus sonography, MR imaging, and surgical findings in children with brachial plexus birth injury.Materials and methodsThis prospective study included 55 consecutive patients (girls/boys = 32:23; mean age, 2.1 ± 0.8 months) with brachial plexus birth injury between May 2014 and April 2017. The patients were classified according to the Narakas classification and were followed up at 4- to 6-week intervals for recovery by the Modified Mallet system and sonography without specific preparation for evaluation. All patients had MR imaging under general anesthesia. Nerve root avulsion-retraction, pseudomeningocele, and periscalene soft tissue were accepted brachial plexus injury findings on imaging. Interobserver agreement for MR imaging and the agreement between imaging and surgical findings were estimated using the κ statistic. The diagnostic accuracy of sonography and MR imaging was calculated on the basis of the standard reference, which was the surgical findings.ResultsForty-three patients had pre- and postganglionic injury, 12 had only postganglionic injury findings, and 47% of patients underwent an operation. On sonography, no patients had preganglionic injury, but all patients had postganglionic injury findings. For postganglionic injury, the concordance rates between imaging and the surgical findings ranged from 84% to 100%, and the diagnostic accuracy of sonography and MR imaging was 89% and 100%, respectively. For preganglionic injury, the diagnostic accuracy of MR imaging was 92%. Interobserver agreement and the agreement between imaging and the surgical findings were almost perfect for postganglionic injury (κ = 0.81-1, P < .001).ConclusionsHigh-resolution sonography can identify and locate the postganglionic injury associated with the upper and middle trunks. The ability of sonography to evaluate pre- and the postganglionic injury associated with the lower trunk was quite limited. Sonography can be used as a complement to MR imaging; thus, the duration of the MR imaging examination and the need for sedation can be reduced by sonography.

Dataset Information

Pain Relief Dependent on IL-17-CD4⁺ T Cell-?-Endorphin Axis in Rat Model of Brachial Plexus Root Avulsion After Electroacupuncture Therapy.

Background and purpose

Methods

Results

Conclusion

Publications

Pain Relief Dependent on IL-17-CD4<sup>+</sup> T Cell-β-Endorphin Axis in Rat Model of Brachial Plexus Root Avulsion After Electroacupuncture Therapy.

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Pain Relief Dependent on IL-17-CD4+ T Cell-?-Endorphin Axis in Rat Model of Brachial Plexus Root Avulsion After Electroacupuncture Therapy.

Background and purpose

Methods

Results

Conclusion

Publications

Pain Relief Dependent on IL-17-CD4<sup>+</sup> T Cell-β-Endorphin Axis in Rat Model of Brachial Plexus Root Avulsion After Electroacupuncture Therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Pain Relief Dependent on IL-17-CD4⁺ T Cell-?-Endorphin Axis in Rat Model of Brachial Plexus Root Avulsion After Electroacupuncture Therapy.