Abstract
The unpleasant sensory and emotional experience of pain is initiated by excitation of primary afferent nociceptive neurons. Nerve damage or inflammation induces changes in nociceptive DRG neurons which contribute to both peripheral and central sensitization of pain-sensitive pathways. Recently, blockade of microRNA synthesis has been found to modulate the response of nociceptive neurons to inflammatory stimuli. However, little is known about the contributions of individual miRNAs to painful conditions. We compared miRNA expression in mouse sensory neurons and focussed on the localisation and control of miR-143. Using miRNA-arrays we compared the microRNA expression profile of intact lumbar DRG with one-day-old DRG cultures and found that nine miRNAs including miR-143 showed lower expression levels in cultures. Subsequent RT-qPCR confirmed array data and in-situ hybridisation localised miR-143 in the cytosol of sensory DRG neurons in situ and in vitro. Analysis of microbead-enriched neuron cultures showed significantly higher expression levels of miR-143 in isolectin B4 (I-B4) binding sensory neurons compared with neurons in the I-B4 negative flow-through fraction. In animal models of peripheral inflammation (injection of Complete Freund’s Adjuvant, CFA) and nerve damage (transection of the sciatic nerve), we found that expression levels of miR-143 were significantly lower in DRGs ipsilateral to CFA injection or after nerve damage. Taken together, our data demonstrate for the first time miR-143 expression in nociceptive neurons. Since expression levels of miR-143 were higher in I-B4 positive neurons and declined in response to inflammation but not axotomy, miR-143 could selectively contribute to mRNA regulation in specific populations of nociceptors.
Similar content being viewed by others
References
Aldrich BT, Frakes EP, Kasuya J, Hammond DL, Kitamoto T (2009) Changes in expression of sensory organ-specific microRNAs in rat dorsal root ganglia in association with mechanical hypersensitivity induced by spinal nerve ligation. Neuroscience 164:711–723
Asher RA, Morgenstern DA, Shearer MC, Adcock KH, Pesheva P, Fawcett JW (2002) Versican is upregulated in CNS injury and is a product of oligodendrocyte lineage cells. J Neurosci 22:2225–2236
Bai G, Ambalavanar R, Wei D, Dessem D (2007) Downregulation of selective microRNAs in trigeminal ganglion neurons following inflammatory muscle pain. Mol Pain 3:15
Bogen O, Dreger M, Gillen C, Schroder W, Hucho F (2005) Identification of versican as an isolectin B4-binding glycoprotein from mammalian spinal cord tissue. FEBS J 272:1090–1102
Braz JM, Basbaum AI (2010) Differential ATF3 expression in dorsal root ganglion neurons reveals the profile of primary afferents engaged by diverse noxious chemical stimuli. Pain 150:290–301
Costigan M, Befort K, Karchewski L, Griffin RS, D'Urso D, Allchorne A, Sitarski J, Mannion JW, Pratt RE, Woolf CJ (2002) Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. BMC Neurosci 3:16
Dours-Zimmermann MT, Maurer K, Rauch U, Stoffel W, Fassler R, Zimmermann DR (2009) Versican V2 assembles the extracellular matrix surrounding the nodes of ranvier in the CNS. J Neurosci 29:7731–7742
Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, Burge CB, Bartel DP (2005) The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science 310:1817–1821
Fukuoka T, Tokunaga A, Kondo E, Miki K, Tachibana T, Noguchi K (1998) Change in mRNAs for neuropeptides and the GABA(A) receptor in dorsal root ganglion neurons in a rat experimental neuropathic pain model. Pain 78:13–26
Gu WL, Fu SL, Wang YX, Li Y, Wang XF, Xu XM, Lu PH (2007) Expression and regulation of versican in neural precursor cells and their lineages. Acta Pharmacol Sin 28:1519–1530
Hebert SS, De Strooper B (2007) Molecular biology. miRNAs in neurodegeneration. Science 317:1179–1180
Komori N, Takemori N, Kim HK, Singh A, Hwang SH, Foreman RD, Chung K, Chung JM, Matsumoto H (2007) Proteomics study of neuropathic and nonneuropathic dorsal root ganglia: altered protein regulation following segmental spinal nerve ligation injury. Physiol Genomics 29:215–230
Kress M, Guenther S (1999) Role of [Ca2+]i in the ATP-induced heat sensitization process of rat nociceptive neurons. J Neurophysiol 81:2612–2619
Lau P, Hudson LD (2010) MicroRNAs in neural cell differentiation. Brain Res 1338:14–19
Li X, Jin P (2010) Roles of small regulatory RNAs in determining neuronal identity. Nat Rev Neurosci 11:329–338
Li Q, Zhao X, Zhong LJ, Yang HY, Wang Q, Pu XP (2009) Effects of chronic morphine treatment on protein expression in rat dorsal root ganglia. Eur J Pharmacol 612:21–28
Obernosterer G, Martinez J, Alenius M (2007) Locked nucleic acid-based in situ detection of microRNAs in mouse tissue sections. Nat Protoc 2:1508–1514
Persson AK, Gebauer M, Jordan S, Metz-Weidmann C, Schulte AM, Schneider HC, Ding-Pfennigdorff D, Thun J, Xu XJ, Wiesenfeld-Hallin Z, Darvasi A, Fried K, Devor M (2009) Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain. Mol Pain 5:7
Pfaffl MW, Horgan GW, Dempfle L (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30:e36
Rigaud M, Gemes G, Barabas ME, Chernoff DI, Abram SE, Stucky CL, Hogan QH (2008) Species and strain differences in rodent sciatic nerve anatomy: implications for studies of neuropathic pain. Pain 136:188–201
Schratt G (2009) Fine-tuning neural gene expression with microRNAs. Curr Opin Neurobiol 19:213–219
Sethupathy P, Megraw M, Hatzigeorgiou AG (2006) A guide through present computational approaches for the identification of mammalian microRNA targets. Nat Methods 3:881–886
Smith ES, Lewin GR (2009) Nociceptors: a phylogenetic view. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 195:1089–1106
Tao YX, Rumbaugh G, Wang GD, Petralia RS, Zhao C, Kauer FW, Tao F, Zhuo M, Wenthold RJ, Raja SN, Huganir RL, Bredt DS, Johns RA (2003) Impaired NMDA receptor-mediated postsynaptic function and blunted NMDA receptor-dependent persistent pain in mice lacking postsynaptic density-93 protein. J Neurosci 23:6703–6712
Vallotton P, Lagerstrom R, Sun C, Buckley M, Wang D, De Silva M, Tan SS, Gunnersen JM (2007) Automated analysis of neurite branching in cultured cortical neurons using HCA-Vision. Cytometry A 71:889–895
Wang G, Mao W, Zheng S (2008) MicroRNA-183 regulates Ezrin expression in lung cancer cells. FEBS Lett 582:3663–3668
Wang X, Hu G, Zhou J (2010) Repression of versican expression by microRNA-143. J Biol Chem 285:23241–23250
Woolf CJ, Ma Q (2007) Nociceptors–noxious stimulus detectors. Neuron 55:353–364
Yamagata T, Yoshizawa J, Ohashi S, Yanaga K, Ohki T (2010) Expression patterns of microRNAs are altered in hypoxic human neuroblastoma cells. Pediatr Surg Int 26:1179–1184
Zhang X, Xiao HS (2005) Gene array analysis to determine the components of neuropathic pain signaling. Curr Opin Mol Ther 7:532–537
Zhang Y, Wang YH, Zhang XH, Ge HY, Arendt-Nielsen L, Shao JM, Yue SW (2008) Proteomic analysis of differential proteins related to the neuropathic pain and neuroprotection in the dorsal root ganglion following its chronic compression in rats. Exp Brain Res 189:199–209
Zhao J, Lee MC, Momin A, Cendan CM, Shepherd ST, Baker MD, Asante C, Bee L, Bethry A, Perkins JR, Nassar MA, Abrahamsen B, Dickenson A, Cobb BS, Merkenschlager M, Wood JN (2010) Small RNAs control sodium channel expression, nociceptor excitability, and pain thresholds. J Neurosci 30:10860–10871
Zimmermann M (2001) Pathobiology of neuropathic pain. Eur J Pharmacol 429:23–37
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tam Tam, S., Bastian, I., Zhou, X.F. et al. MicroRNA-143 expression in dorsal root ganglion neurons. Cell Tissue Res 346, 163–173 (2011). https://doi.org/10.1007/s00441-011-1263-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-011-1263-x