Skip to main content
Log in

Deep Sequencing Identification of Differentially Expressed miRNAs in the Spinal Cord of Resiniferatoxin-Treated Rats in Response to Electroacupuncture

  • Original Article
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Electroacupuncture (EA) is an effective treatment to relieve pain in patients with postherpetic neuralgia. However, the mechanisms of EA involved therein are still unknown. We first injected resiniferatoxin (RTX) into Sprague Dawley rats to construct the neuralgia model. One week after injection, the rats were treated with EA at the “Huantiao” (GB30) and “Yanglingquan” (GB34) acupoints for 5 weeks. Nociceptive behavioral tests were performed to analyze the changes in thermal sensitivity and mechanical allodynia after RTX induction and EA treatment. Deep sequencing was performed to identify differentially expressed miRNAs in the spinal cord of RTX-induced rats in response to EA treatment. The nociceptive behavioral tests showed that EA at the left GB30 and GB34 acupoints significantly reduced RTX-induced tactile sensitivity and increased RTX-inhibited thermal sensitivity. The sequencing data indicated that RTX resulted in one upregulated and five downregulated miRNAs, and EA treatment resulted in two upregulated miRNAs. Furthermore, seven upregulated and two downregulated miRNAs were found between rats subjected to EA and sham operation. Functional analysis suggested that the targets of differentially expressed miRNAs were enriched in many nervous system–related pathways. The pathway-gene-miRNA net analysis showed that miR-7a-5p had the most target genes. Moreover, miR-233-3p was downregulated after RTX injection and upregulated by EA treatment. We speculated that the upregulation of miR-7a-5p and miR-233-3p is involved in the analgesic effects of EA. Our analysis on the EA-induced differential expression of miRNAs provides novel insights into the mechanisms of EA analgesia in postherpetic neuralgia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Baron R, Saguer M (1993) Postherpetic neuralgia. Are C-nociceptors involved in signalling and maintenance of tactile allodynia? Brain 116(Pt 6):1477–1496

    Article  PubMed  Google Scholar 

  • Berman BM, Lao L, Langenberg P, Lee WL, Gilpin AM, Hochberg MC (2004) Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee: a randomized, controlled trial. Ann Intern Med 141:901–910

    Article  PubMed  Google Scholar 

  • Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53:55–63

    Article  CAS  Google Scholar 

  • Chen SR, Pan HL (2005) Effect of systemic and intrathecal gabapentin on allodynia in a new rat model of postherpetic neuralgia. Brain Res 1042:108–113

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Zhang J, Li F, Qiu Y, Wang L, Li YH, Shi J, Pan HL, Li M (2009) Endogenous anandamide and cannabinoid receptor-2 contribute to electroacupuncture analgesia in rats. J Pain 10:732–739

    Article  CAS  PubMed  Google Scholar 

  • de Chevigny A, Core N, Follert P, Gaudin M, Barbry P, Beclin C, Cremer H (2012) miR-7a regulation of Pax6 controls spatial origin of forebrain dopaminergic neurons. Nat Neurosci 15:1120–1126

    Article  CAS  Google Scholar 

  • Grachev Iu V, Kukushkin ML, Sudarikov AP, Zhuravlev VF, Gerasimenko M (1998) Clinical course and treatment of herpetic trigeminal ganglionic neuropathy. Zh Nevrol Psikhiatr Im SS Korsakova 98:4–8

    CAS  Google Scholar 

  • Hargreaves K, Dubner R, Brown F, Flores C, Joris J (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32:77–88

    Article  CAS  Google Scholar 

  • Khan GM, Chen SR, Pan HL (2002) Role of primary afferent nerves in allodynia caused by diabetic neuropathy in rats. Neuroscience 114:291–299

    Article  CAS  PubMed  Google Scholar 

  • Klompas M, Kulldorff M, Vilk Y, Bialek SR, Harpaz R (2011) Herpes zoster and postherpetic neuralgia surveillance using structured electronic data. Mayo Clin Proc 86:1146–1153

    Article  PubMed  PubMed Central  Google Scholar 

  • Laszlo K, Dorothy CB, Andrew JM, Stephen TC, Jacob B, Michael G, Ofer MW, John KN, Zoltan O, Michael JI (2004) Deletion of vanilloid receptor 1_expressing primary afferent neurons for pain control. J Clin Invest 113(9):1344–1352

    Article  Google Scholar 

  • Levin MJ, Smith JG, Kaufhold RM, Barber D, Hayward AR, Chan CY, Chan IS, Li DJ, Wang W, Keller PM, Shaw A, Silber JL, Schlienger K, Chalikonda I, Vessey SJ, Caulfield MJ (2003) Decline in varicella-zoster virus (VZV)-specific cell-mediated immunity with increasing age and boosting with a high-dose VZV vaccine. J Infect Dis 188:1336–1344

    Article  PubMed  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408

    Article  CAS  Google Scholar 

  • Lopez-Gonzalez MJ, Landry M, Favereaux A (2017) MicroRNA and chronic pain: from mechanisms to therapeutic potential. Pharmacol Ther 180:1–15

    Article  CAS  PubMed  Google Scholar 

  • Ma C, Li CX, Yi JL, Yan LP (2008) Effects of electroacupuncture on glutamate and aspartic acid contents in the dorsal root ganglion and spinal cord in rats with neuropathic pain. Zhen ci yan jiu 33:250–254

  • Pan HL, Khan GM, Alloway KD, Chen SR (2003) Resiniferatoxin induces paradoxical changes in thermal and mechanical sensitivities in rats: mechanism of action. J Neurosci 23:2911–2919

    Article  CAS  PubMed  Google Scholar 

  • Park JH, Han JB, Kim SK, Park JH, Go DH, Sun B, Min BI (2010) Spinal GABA receptors mediate the suppressive effect of electroacupuncture on cold allodynia in rats. Brain Res 1322:24–29

    Article  CAS  PubMed  Google Scholar 

  • Sakai A, Saitow F, Miyake N, Miyake K, Shimada T, Suzuki H (2013) miR-7a alleviates the maintenance of neuropathic pain through regulation of neuronal excitability. Brain 136:2738–2750

    Article  PubMed  Google Scholar 

  • Shukla GC, Singh J, Barik S (2011) MicroRNAs: processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol 3:83–92

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tanaka N, Yamaga M, Tateyama S, Uno T, Tsuneyoshi I, Takasaki M (2010) The effect of pulsed radiofrequency current on mechanical allodynia induced with resiniferatoxin in rats. Anesth Analg 111:784–790

    Article  PubMed  Google Scholar 

  • Vickers AJ, Cronin AM, Maschino AC, Lewith G, MacPherson H, Foster NE, Sherman KJ, Witt CM, Linde K, Acupuncture Trialists C (2012) Acupuncture for chronic pain: individual patient data meta-analysis. Arch Intern Med 172:1444–1453

    Article  PubMed  PubMed Central  Google Scholar 

  • Virgin HW, Wherry EJ, Ahmed R (2009) Redefining chronic viral infection. Cell 138:30–50

    Article  CAS  PubMed  Google Scholar 

  • Wang CY, Fang JQ (2012) Analysis on therapeutic effect of variable-frequency electroacupuncture combined with herbal-moxa moxibustion for post-zoster neuralgia. Zhen ci yan jiu 37:64–66

  • Wang L, Zhang Y, Dai J, Yang J, Gang S (2006) Electroacupuncture (EA) modulates the expression of NMDA receptors in primary sensory neurons in relation to hyperalgesia in rats. Brain Res 1120:46–53

    Article  CAS  PubMed  Google Scholar 

  • Wu CH, Lv ZT, Zhao Y, Gao Y, Li JQ, Gao F, Meng XF, Tian B, Shi J, Pan HL, Li M (2013) Electroacupuncture improves thermal and mechanical sensitivities in a rat model of postherpetic neuralgia. Mol Pain 9:18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie XJ, Ma LG, Xi K, Fan DM, Li JG, Zhang Q, Zhang W (2017) Effects of microRNA-223 on morphine analgesic tolerance by targeting NLRP3 in a rat model of neuropathic pain. Mol Pain 13:1744806917706582

    Article  PubMed  PubMed Central  Google Scholar 

  • Yan LP, Wu XT, Yin ZY, Ma C (2011) Effect of electroacupuncture on the levels of amino acid neurotransmitters in the spinal cord in rats with chronic constrictive injury. Zhen ci yan jiu 353–356(379):36

  • Yawn BP, Saddier P, Wollan PC, St Sauver JL, Kurland MJ, Sy LS (2007) A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clin Proc 82:1341–1349

  • Yu-Lin H, Chiang H, Lue J-H, Hsieh S-T (2012) P2X3-mediated peripheral sensitization of neuropathic pain in resiniferatoxin-induced neuropathy. Exp Neurol 235(1):316–325

    Article  CAS  Google Scholar 

  • Zhang R, Lao L, Ren K, Berman BM (2014) Mechanisms of acupuncture-electroacupuncture on persistent pain. Anesthesiology 120:482–503

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao ZQ (2008) Neural mechanism underlying acupuncture analgesia. Prog Neurobiol 85:355–375

    Article  PubMed  Google Scholar 

  • Zimmermann M (1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16:109–110

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Jing Zou and Guofu Huang designed the experiments. Xueyang Dong and Yanling Li drafted and revised the manuscript. Siqi Tong and Jingwen Wang assisted with data analysis and interpretation. Mingxuan Liao was a major contributor to the writing of the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Guofu Huang.

Ethics declarations

All experimental procedures were approved by the Animal Care Committee at Huazhong University of Science and Technology and conformed to the ethical guidelines of the International Association for the Study of Pain.

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Significance

The present study identified changes in miRNA expression induced by electroacupuncture in the spinal cord in a rat model of postherpetic neuralgia. The results elucidate the potential role of miRNAs in electroacupuncture-mediated analgesia.

Electronic Supplementary Material

ESM 1

(XLSX 11.0 kb)

ESM 2

(XLSX 21.0 kb)

ESM 3

(XLSX 20.4 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zou, J., Dong, X., Li, Y. et al. Deep Sequencing Identification of Differentially Expressed miRNAs in the Spinal Cord of Resiniferatoxin-Treated Rats in Response to Electroacupuncture. Neurotox Res 36, 387–395 (2019). https://doi.org/10.1007/s12640-019-00052-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-019-00052-8

Keywords

Navigation