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Published in: Neurotoxicity Research 2/2019

01-08-2019 | Original Article

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

Authors: Jing Zou, Xueyang Dong, Yanling Li, Siqi Tong, Jingwen Wang, Mingxuan Liao, Guofu Huang

Published in: Neurotoxicity Research | Issue 2/2019

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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.
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Literature
go back to reference Baron R, Saguer M (1993) Postherpetic neuralgia. Are C-nociceptors involved in signalling and maintenance of tactile allodynia? Brain 116(Pt 6):1477–1496CrossRefPubMed Baron R, Saguer M (1993) Postherpetic neuralgia. Are C-nociceptors involved in signalling and maintenance of tactile allodynia? Brain 116(Pt 6):1477–1496CrossRefPubMed
go back to reference 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 141:901–910CrossRefPubMed 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 141:901–910CrossRefPubMed
go back to reference Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53:55–63CrossRef Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53:55–63CrossRef
go back to reference Chen SR, Pan HL (2005) Effect of systemic and intrathecal gabapentin on allodynia in a new rat model of postherpetic neuralgia. Brain Res 1042:108–113CrossRefPubMed Chen SR, Pan HL (2005) Effect of systemic and intrathecal gabapentin on allodynia in a new rat model of postherpetic neuralgia. Brain Res 1042:108–113CrossRefPubMed
go back to reference 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 10:732–739CrossRefPubMed 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 10:732–739CrossRefPubMed
go back to reference 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 15:1120–1126CrossRef 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 15:1120–1126CrossRef
go back to reference 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 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
go back to reference Hargreaves K, Dubner R, Brown F, Flores C, Joris J (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32:77–88CrossRef Hargreaves K, Dubner R, Brown F, Flores C, Joris J (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32:77–88CrossRef
go back to reference Khan GM, Chen SR, Pan HL (2002) Role of primary afferent nerves in allodynia caused by diabetic neuropathy in rats. Neuroscience 114:291–299CrossRefPubMed Khan GM, Chen SR, Pan HL (2002) Role of primary afferent nerves in allodynia caused by diabetic neuropathy in rats. Neuroscience 114:291–299CrossRefPubMed
go back to reference Klompas M, Kulldorff M, Vilk Y, Bialek SR, Harpaz R (2011) Herpes zoster and postherpetic neuralgia surveillance using structured electronic data. Mayo Clin Proc 86:1146–1153CrossRefPubMedPubMedCentral Klompas M, Kulldorff M, Vilk Y, Bialek SR, Harpaz R (2011) Herpes zoster and postherpetic neuralgia surveillance using structured electronic data. Mayo Clin Proc 86:1146–1153CrossRefPubMedPubMedCentral
go back to reference 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):1344–1352CrossRef 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):1344–1352CrossRef
go back to reference 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 188:1336–1344CrossRefPubMed 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 188:1336–1344CrossRefPubMed
go back to reference 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 25:402–408CrossRef 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 25:402–408CrossRef
go back to reference Lopez-Gonzalez MJ, Landry M, Favereaux A (2017) MicroRNA and chronic pain: from mechanisms to therapeutic potential. Pharmacol Ther 180:1–15CrossRefPubMed Lopez-Gonzalez MJ, Landry M, Favereaux A (2017) MicroRNA and chronic pain: from mechanisms to therapeutic potential. Pharmacol Ther 180:1–15CrossRefPubMed
go back to reference 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 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
go back to reference 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 23:2911–2919CrossRefPubMed 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 23:2911–2919CrossRefPubMed
go back to reference 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 1322:24–29CrossRefPubMed 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 1322:24–29CrossRefPubMed
go back to reference 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 136:2738–2750CrossRefPubMed 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 136:2738–2750CrossRefPubMed
go back to reference Shukla GC, Singh J, Barik S (2011) MicroRNAs: processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol 3:83–92PubMedPubMedCentral Shukla GC, Singh J, Barik S (2011) MicroRNAs: processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol 3:83–92PubMedPubMedCentral
go back to reference 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 111:784–790CrossRefPubMed 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 111:784–790CrossRefPubMed
go back to reference 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 172:1444–1453CrossRefPubMedPubMedCentral 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 172:1444–1453CrossRefPubMedPubMedCentral
go back to reference 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 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
go back to reference 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 1120:46–53CrossRefPubMed 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 1120:46–53CrossRefPubMed
go back to reference 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 9:18CrossRefPubMedPubMedCentral 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 9:18CrossRefPubMedPubMedCentral
go back to reference 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 13:1744806917706582CrossRefPubMedPubMedCentral 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 13:1744806917706582CrossRefPubMedPubMedCentral
go back to reference 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 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
go back to reference 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 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
go back to reference 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):316–325CrossRef 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):316–325CrossRef
go back to reference Zimmermann M (1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16:109–110CrossRef Zimmermann M (1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16:109–110CrossRef
Metadata
Title
Deep Sequencing Identification of Differentially Expressed miRNAs in the Spinal Cord of Resiniferatoxin-Treated Rats in Response to Electroacupuncture
Authors
Jing Zou
Xueyang Dong
Yanling Li
Siqi Tong
Jingwen Wang
Mingxuan Liao
Guofu Huang
Publication date
01-08-2019
Publisher
Springer US
Published in
Neurotoxicity Research / Issue 2/2019
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI
https://doi.org/10.1007/s12640-019-00052-8

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