Exploring the Mechanisms of Electroacupuncture-Induced Analgesia Through RNA Sequencing of the Periaqueductal Gray

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2018 Jan 4

PMID 29295561

Citations 15

Authors

Man-Li Hu

Hong-Mei Zhu

Qiu-Lin Zhang

Jing-Jing Liu

Yi Ding

Ju-Ming Zhong

Vitaly Vodyanoy

Ming-Xing Ding

Affiliations

Soon will be listed here.

Abstract

Electroacupuncture (EA) can relieve various pains. However, its mechanism in terms of the transcriptome is still not well-known. To explore the full profile of EA-induced molecular modification in the central nerve system, three twins of goats were selected for a match-paired experiment: EA stimulation (60 Hz, 30 min) and none-EA (control). Goats in the EA group showed an increased ( < 0.05) nociceptive threshold compared with the control goats. Experimental goats were sacrificed at 4 h of the experiment, and the periaqueductal grays were harvested for RNA sequencing. As a result, 2651 differentially expressed genes (1803 up-regulated and 848 down-regulated genes) were found and enriched in 30 Kyoto Encyclopedia of Genes and Genomes pathways and 149 gene ontology terms. EA-regulated five neuropeptide genes (, , , and ) were validated with quantitative PCR. Furthermore, up-regulated glutamate receptors, glutamate transporters, γ-aminobutyric acid () receptors, GABA transporters, synaptotagmins or mitogen-activated protein kinase () genes might contribute to EA-induced analgesia through regulating the glutamatergic synapse, GABAergic synapse, MAPKs, ribosome or ubiquitin-proteasome pathways. Our findings reveal a full profile of molecular modification in response to EA and provide a solid experimental framework for exploring the mechanisms underlying EA-induced analgesia.

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References

Samineni V, Grajales-Reyes J, Copits B, OBrien D, Trigg S, Gomez A . Divergent Modulation of Nociception by Glutamatergic and GABAergic Neuronal Subpopulations in the Periaqueductal Gray. eNeuro. 2017; 4(2). PMC: 5370278. DOI: 10.1523/ENEURO.0129-16.2017. View

Hernandez-Leon A, Fernandez-Guasti A, Gonzalez-Trujano M . Rutin antinociception involves opioidergic mechanism and descending modulation of ventrolateral periaqueductal grey matter in rats. Eur J Pain. 2015; 20(2):274-83. DOI: 10.1002/ejp.720. View

Anders S, Pyl P, Huber W . HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2014; 31(2):166-9. PMC: 4287950. DOI: 10.1093/bioinformatics/btu638. View

Lecker S, Goldberg A, Mitch W . Protein degradation by the ubiquitin-proteasome pathway in normal and disease states. J Am Soc Nephrol. 2006; 17(7):1807-19. DOI: 10.1681/ASN.2006010083. View

Zeng J, Cui L, Feng Y, Ding M . Electroacupuncture relieves neuropathic pain via upregulation of glutamate transporters in the spinal cord of rats. Neurosci Lett. 2016; 620:38-42. DOI: 10.1016/j.neulet.2016.03.041. View

Kim H, Kim Y, Jang J, Shin H, Choi B . Electroacupuncture Confers Antinociceptive Effects via Inhibition of Glutamate Transporter Downregulation in Complete Freund's Adjuvant-Injected Rats. Evid Based Complement Alternat Med. 2012; 2012:643973. PMC: 3432559. DOI: 10.1155/2012/643973. View

Sjolund B, Eriksson M . The influence of naloxone on analgesia produced by peripheral conditioning stimulation. Brain Res. 1979; 173(2):295-301. DOI: 10.1016/0006-8993(79)90629-2. View

Chen X, Han J . Analgesia induced by electroacupuncture of different frequencies is mediated by different types of opioid receptors: another cross-tolerance study. Behav Brain Res. 1992; 47(2):143-9. DOI: 10.1016/s0166-4328(05)80120-2. View

Wang J, Chen S, Gao Y, Qiao L, Zhang J, Liu J . Effect of Repeated Electroacupuncture Intervention on Hippocampal ERK and p38MAPK Signaling in Neuropathic Pain Rats. Evid Based Complement Alternat Med. 2015; 2015:641286. PMC: 4487344. DOI: 10.1155/2015/641286. View

10.

Robinson M, McCarthy D, Smyth G . edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2009; 26(1):139-40. PMC: 2796818. DOI: 10.1093/bioinformatics/btp616. View

11.

Zhang R, Lao L, Ren K, Berman B . Mechanisms of acupuncture-electroacupuncture on persistent pain. Anesthesiology. 2013; 120(2):482-503. PMC: 3947586. DOI: 10.1097/ALN.0000000000000101. View

12.

Guidotti A, Forchetti C, Corda M, Konkel D, Bennett C, Costa E . Isolation, characterization, and purification to homogeneity of an endogenous polypeptide with agonistic action on benzodiazepine receptors. Proc Natl Acad Sci U S A. 1983; 80(11):3531-5. PMC: 394079. DOI: 10.1073/pnas.80.11.3531. View

13.

Fernandez-Chacon R, Konigstorfer A, Gerber S, Garcia J, Matos M, Stevens C . Synaptotagmin I functions as a calcium regulator of release probability. Nature. 2001; 410(6824):41-9. DOI: 10.1038/35065004. View

14.

Lee J, Choi D, Oh T, Yune T . Analgesic effect of acupuncture is mediated via inhibition of JNK activation in astrocytes after spinal cord injury. PLoS One. 2013; 8(9):e73948. PMC: 3767587. DOI: 10.1371/journal.pone.0073948. View

15.

Zhang R, Wang L, Wang X, Ren K, Berman B, Lao L . Electroacupuncture combined with MK-801 prolongs anti-hyperalgesia in rats with peripheral inflammation. Pharmacol Biochem Behav. 2005; 81(1):146-51. DOI: 10.1016/j.pbb.2005.03.002. View

16.

Yang J, Yang Y, Chu J, Wang G, Xu H, Liu W . Endogenous opiate peptides in the spinal cord are involved in the analgesia of hypothalamic paraventricular nucleus in the rat. Peptides. 2009; 30(4):740-4. DOI: 10.1016/j.peptides.2009.01.004. View

17.

Park J, Han J, Kim S, Park J, Go D, Sun B . Spinal GABA receptors mediate the suppressive effect of electroacupuncture on cold allodynia in rats. Brain Res. 2010; 1322:24-9. DOI: 10.1016/j.brainres.2010.02.001. View

18.

Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg S . TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013; 14(4):R36. PMC: 4053844. DOI: 10.1186/gb-2013-14-4-r36. View

19.

Mortazavi A, Williams B, McCue K, Schaeffer L, Wold B . Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods. 2008; 5(7):621-8. DOI: 10.1038/nmeth.1226. View

20.

Xu K, Liang T, Wang K, Tian D . Effect of pre-electroacupuncture on p38 and c-Fos expression in the spinal dorsal horn of rats suffering from visceral pain. Chin Med J (Engl). 2010; 123(9):1176-81. View