Mus musculus-microRNA-449a ameliorates neuropathic pain by decreasing the level of KCNMA1 and TRPA1, and increasing the level of TPTE

Lu,Shan; Ma,Sichao; Wang,Yunyun; Huang,Tao; Zhu,Zhihua; Zhao,Guoqing

doi:10.3892/mmr.2017.6559

Mus musculus-microRNA-449a ameliorates neuropathic pain by decreasing the level of KCNMA1 and TRPA1, and increasing the level of TPTE

Authors:
- Shan Lu
- Sichao Ma
- Yunyun Wang
- Tao Huang
- Zhihua Zhu
- Guoqing Zhao
View Affiliations

Affiliations: Department of Anesthesia, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Nephrology, The First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China, Department of Emergency, The First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China
Published online on: May 10, 2017 https://doi.org/10.3892/mmr.2017.6559
Pages: 353-360

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Neuropathic pain is a nerve disorder characterized by the dysregulation of ion channels in dorsal root ganglion (DRG) neurons. MicroRNAs (miRs) may be associated with the molecular mechanisms underlying the altered levels of ion channels; however, the molecular mechanisms remain widely unknown. To investigate these mechanisms, the present study conducted a genomic analysis of miR between a unilateral spared nerve injury (SNI) model and sham control. Differentially expressed miRs between the SNI and sham groups were selected for transfection of DRG cells, a polymerase chain reaction (PCR) array analysis was subsequently performed. A total of three significantly differently expressed genes were selected from the results of the PCR array and further analyzed by reverse transcription‑quantitative PCR. Genomic analysis revealed that Mus musculus miR‑449a (mmu‑miR‑449a) was reduced in the SNI groups compared with the sham controls. The PCR array indicated that mmu‑miR‑449a‑transfection reduced the mRNA expression levels of transient receptor potential cation channel subfamily A member 1 (TRPA1), and calcium‑activated potassium channel subunit α‑1 (KCNMA1) and increased the level of transmembrane phosphatase with tension homology (TPTE) in the DRG cells (P<0.05). qRT‑PCR analysis further indicated that mmu‑miR‑449a transfection caused similar alterations in the mRNA expression levels of TRPA1, KCNMA1 and TPTE in DRG cells, respectively (P<0.05). Therefore, mmu‑miR‑449a may ameliorate neuropathic pain by decreasing the activity of the channel proteins TRPA1 and KCNMA1 and increasing the levels of TPTE. mmu‑miR‑449a may be a potential therapeutic molecule for the alleviation of neuropathic pain.

View Figures

View References

1	Trost Z, Zielke M, Guck A, Nowlin L, Zakhidov D, France CR and Keefe F: The promise and challenge of virtual gaming technologies for chronic pain: The case of graded exposure for low back pain. Pain Manag. 5:197–206. 2015. View Article : Google Scholar : PubMed/NCBI
2	Gerges FJ, Manchanda C, Novak G, Al-Kimawi M, Semenovski M and Williams S: Occult spinal dysraphism: A challenge in pain management. Pain Physician. 18:E225–E228. 2015.PubMed/NCBI
3	Rogachov A, Cheng JC and DeSouza DD: Discriminating neural representations of physical and social pains: How multivariate statistics challenge the ‘shared representation’ theory of pain. J Neurophysiol. 114:2558–2560. 2015. View Article : Google Scholar : PubMed/NCBI
4	Baquie P, Fooks L, Pope J and Tymms G: The challenge of managing mid-foot pain. Aust Fam Physician. 44:106–111. 2015.PubMed/NCBI
5	Hayes K and Gordon DB: Delivering quality pain management: The challenge for nurses. AORN J. 101:328–334; quiz 335–337. 2015. View Article : Google Scholar : PubMed/NCBI
6	Foster DC, Falsetta ML, Woeller CF, Pollock SJ, Song K, Bonham A, Haidaris CG, Stodgell CJ, Messing SP, Iadarola M and Phipps RP: Site-specific mesenchymal control of inflammatory pain to yeast challenge in vulvodynia-afflicted and pain-free women. Pain. 156:386–396. 2015. View Article : Google Scholar : PubMed/NCBI
7	Frisch S: Perceptions of pain. Cultural differences add to the challenge of treating patients' pain. Minn Med. 97:14–16. 2014.
8	Dale O, Moksnes K and Kaasa S: European palliative care research collaborative pain guidelines: Opioid switching to improve analgesia or reduce side effects. A systematic review. Palliat Med. 25:494–503. 2011. View Article : Google Scholar : PubMed/NCBI
9	Rosenbaum D, Dallongeville J, Sabouret P and Bruckert E: Discontinuation of statin therapy due to muscular side effects: A survey in real life. Nutr Metab Cardiovasc Dis. 23:871–875. 2013. View Article : Google Scholar : PubMed/NCBI
10	Caires R, Luis E, Taberner FJ, Fernandez-Ballester G, Ferrer-Montiel A, Balazs EA, Gomis A, Belmonte C and de la Peña E: Hyaluronan modulates TRPV1 channel opening, reducing peripheral nociceptor activity and pain. Nat Commun. 6:80952015. View Article : Google Scholar : PubMed/NCBI
11	Dib-Hajj SD, Black JA and Waxman SG: NaV1.9: A sodium channel linked to human pain. Nat Rev Neurosci. 16:511–519. 2015. View Article : Google Scholar : PubMed/NCBI
12	Cheng CF, Wang WC, Huang CY, Du PH, Yang JH and Tsaur ML: Coexpression of auxiliary subunits KChIP and DPPL in potassium channel Kv4-positive nociceptors and pain-modulating spinal interneurons. J Comp Neurol. 524:846–873. 2015. View Article : Google Scholar : PubMed/NCBI
13	Skerratt SE and West CW: Ion channel therapeutics for pain. Channels (Austin). 9:344–351. 2015. View Article : Google Scholar : PubMed/NCBI
14	Sherkheli MA, Schreiner B, Haq R, Werner M and Hatt H: Borneol inhibits TRPA1, a proinflammatory and noxious pain-sensing cation channel. Pak J Pharm Sci. 28:1357–1363. 2015.PubMed/NCBI
15	Laedermann CJ, Cachemaille M, Kirschmann G, Pertin M, Gosselin RD, Chang I, Albesa M, Towne C, Schneider BL, Kellenberger S, et al: Dysregulation of voltage-gated sodium channels by ubiquitin ligase NEDD4-2 in neuropathic pain. J Clin Invest. 123:3002–3013. 2013. View Article : Google Scholar : PubMed/NCBI
16	Sakai A and Suzuki H: microRNA and Pain. Adv Exp Med Biol. 888:17–39. 2015. View Article : Google Scholar : PubMed/NCBI
17	Linnstaedt SD, Walker MG, Parker JS, Yeh E, Sons RL, Zimny E, Lewandowski C, Hendry PL, Damiron K, Pearson C, et al: MicroRNA circulating in the early aftermath of motor vehicle collision predict persistent pain development and suggest a role for microRNA in sex-specific pain differences. Mol Pain. 11:662015. View Article : Google Scholar : PubMed/NCBI
18	Mallik S and Maulik U: MiRNA-TF-gene network analysis through ranking of biomolecules for multi-informative uterine leiomyoma dataset. J Biomed Inform. 57:308–319. 2015. View Article : Google Scholar : PubMed/NCBI
19	Galicia-Vázquez G, Chu J and Pelletier J: eIF4AII is dispensable for miRNA-mediated gene silencing. RNA. 21:1826–1833. 2015. View Article : Google Scholar : PubMed/NCBI
20	Ding M, Li J, Yu Y, Liu H, Yan Z, Wang J and Qian Q: Integrated analysis of miRNA, gene and pathway regulatory networks in hepatic cancer stem cells. J Transl Med. 13:2592015. View Article : Google Scholar : PubMed/NCBI
21	Yan L, Lee S, Lazzaro DR, Aranda J, Grant MB and Chaqour B: Single and Compound Knockouts of MicroRNA (miRNA)-155 and its Angiogenic Gene Target CCN1 in Mice Alter Vascular and Neovascular Growth in the Retina via Resident Microglia. J Biol Chem. 290:23264–23581. 2015. View Article : Google Scholar : PubMed/NCBI
22	van Spronsen M, van Battum EY, Kuijpers M, Vangoor VR, Rietman ML, Pothof J, Gumy LF, van Ijcken WF, Akhmanova A, Pasterkamp RJ and Hoogenraad CC: Developmental and activity-dependent miRNA expression profiling in primary hippocampal neuron cultures. PLoS One. 8:e749072013. View Article : Google Scholar : PubMed/NCBI
23	Zhang Y, Ueno Y, Liu XS, Buller B, Wang X, Chopp M and Zhang ZG: The microRNA-17-92 cluster enhances axonal outgrowth in embryonic cortical neurons. J Neurosci. 33:6885–6894. 2013. View Article : Google Scholar : PubMed/NCBI
24	Impey S, Davare M, Lesiak A, Fortin D, Ando H, Varlamova O, Obrietan K, Soderling TR, Goodman RH and Wayman GA: An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling. Mol Cell Neurosci. 43:146–156. 2010. View Article : Google Scholar : PubMed/NCBI
25	Kusuda R, Cadetti F, Ravanelli MI, Sousa TA, Zanon S, De Lucca FL and Lucas G: Differential expression of microRNAs in mouse pain models. Mol Pain. 7:172011. View Article : Google Scholar : PubMed/NCBI
26	Wang W, Shi Q, Mattes WB, Mendrick DL and Yang X: Translating extracellular microRNA into clinical biomarkers for drug-induced toxicity: From high-throughput profiling to validation. Biomark Med. 9:1177–1188. 2015. View Article : Google Scholar : PubMed/NCBI
27	Asha S, Sreekumar S and Soniya EV: Unravelling the complexity of microRNA-mediated gene regulation in black pepper (Piper nigrum L.) using high-throughput small RNA profiling. Plant Cell Rep. 35:53–63. 2016. View Article : Google Scholar : PubMed/NCBI
28	Richner M, Bjerrum OJ, Nykjaer A and Vaegter CB: The spared nerve injury (SNI) model of induced mechanical allodynia in mice. J Vis Exp pii. 30922011.
29	Scroggs RS, Todorovic SM, Anderson EG and Fox AP: Variation in IH, IIR and ILEAK between acutely isolated adult rat dorsal root ganglion neurons of different size. J Neurophysiol. 71:271–279. 1994.PubMed/NCBI
30	Zima V, Witschas K, Hynkova A, Zimová L, Barvík I and Vlachova V: Structural modeling and patch-clamp analysis of pain-related mutation TRPA1-N855S reveal inter-subunit salt bridges stabilizing the channel open state. Neuropharmacology. 93:294–307. 2015. View Article : Google Scholar : PubMed/NCBI
31	Kanthesh BM, Sandle GI and Rajendran VM: Enhanced K(+) secretion in dextran sulfate-induced colitis reflects upregulation of large conductance apical K(+) channels (BK; Kcnma1). Am J Physiol Cell Physiol. 305:C972–C980. 2013. View Article : Google Scholar : PubMed/NCBI
32	Tsantoulas C: Emerging potassium channel targets for the treatment of pain. Curr Opin Support Palliat Care. 9:147–154. 2015. View Article : Google Scholar : PubMed/NCBI
33	Pereira V, Busserolles J, Christin M, Devilliers M, Poupon L, Legha W, Alloui A, Aissouni Y, Bourinet E, Lesage F, et al: Role of the TREK2 potassium channel in cold and warm thermosensation and in pain perception. Pain. 155:2534–2544. 2014. View Article : Google Scholar : PubMed/NCBI
34	Livak KJ and Schmittgen TD: Analysis of gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
35	Abramowski P, Ogrodowczyk C, Martin R and Pongs O: A truncation variant of the cation channel P2RX5 is upregulated during T cell activation. PLoS One. 9:e1046922014. View Article : Google Scholar : PubMed/NCBI
36	Zhao Z, Ma X, Sung D, Li M, Kosti A, Lin G, Chen Y, Pertsemlidis A, Hsiao TH and Du L: microRNA-449a functions as a tumor suppressor in neuroblastoma through inducing cell differentiation and cell cycle arrest. RNA Biol. 12:538–554. 2015. View Article : Google Scholar : PubMed/NCBI
37	Lai CY, Yu SL, Hsieh MH, Chen CH, Chen HY, Wen CC, Huang YH, Hsiao PC, Hsiao CK, Liu CM, et al: MicroRNA expression aberration as potential peripheral blood biomarkers for schizophrenia. PLoS One. 6:e216352011. View Article : Google Scholar : PubMed/NCBI
38	Nassini R, Materazzi S, Benemei S and Geppetti P: The TRPA1 channel in inflammatory and neuropathic pain and migraine. Rev Physiol Biochem Pharmacol. 167:1–43. 2014. View Article : Google Scholar : PubMed/NCBI
39	Kogure W, Wang S, Tanaka K, Hao Y, Yamamoto S, Nishiyama N, Noguchi K and Dai Y: Elevated H2 O2 levels in trinitrobenzene sulfate-induced colitis rats contributes to visceral hyperalgesia through interaction with the ransient receptor potential ankyrin 1 cation channel. J Gastroenterol Hepatol. 31:1147–1453. 2016. View Article : Google Scholar : PubMed/NCBI
40	DeBerry JJ, Saloman JL, Dragoo BK, Albers KM and Davis BM: Artemin immunotherapy is effective in preventing and reversing cystitis-induced bladder hyperalgesia via TRPA1 regulation. J Pain. 16:628–636. 2015. View Article : Google Scholar : PubMed/NCBI
41	Langford DJ, Paul SM, West CM, Dunn LB, Levine JD, Kober KM, Dodd MJ, Miaskowski C and Aouizerat BE: Variations in potassium channel genes are associated with distinct trajectories of persistent breast pain after breast cancer surgery. Pain. 156:371–380. 2015. View Article : Google Scholar : PubMed/NCBI