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Extracellular microRNAs activate nociceptor neurons to elicit pain via TLR7 and TRPA1.
Neuron. 2014 Apr 02; 82(1):47-54.N

Abstract

Intracellular microRNAs (miRNAs) are key regulators of gene expression. The role of extracellular miRNAs in neuronal activation and sensory behaviors are unknown. Here we report an unconventional role of extracellular miRNAs for rapid excitation of nociceptor neurons via toll-like receptor-7 (TLR7) and its coupling to TRPA1 ion channel. miRNA-let-7b induces rapid inward currents and action potentials in dorsal root ganglion (DRG) neurons. These responses require the GUUGUGU motif, only occur in neurons coexpressing TLR7 and TRPA1, and are abolished in mice lacking Tlr7 or Trpa1. Furthermore, let-7b induces TLR7/TRPA1-dependent single-channel activities in DRG neurons and HEK293 cells overexpressing TLR7/TRPA1. Intraplantar injection of let-7b elicits rapid spontaneous pain via TLR7 and TRPA1. Finally, let-7b can be released from DRG neurons by neuronal activation, and let-7b inhibitor reduces formalin-induced TRPA1 currents and spontaneous pain. Thus, secreted extracellular miRNAs may serve as novel pain mediators via activating TLR7/TRPA1 in nociceptor neurons.

Authors+Show Affiliations

Pain Signaling and Plasticity Laboratory, Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.Pain Signaling and Plasticity Laboratory, Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.Pain Signaling and Plasticity Laboratory, Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.Pain Signaling and Plasticity Laboratory, Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.Pain Signaling and Plasticity Laboratory, Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.Pain Signaling and Plasticity Laboratory, Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.Pain Signaling and Plasticity Laboratory, Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: ru-rong.ji@duke.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24698267

Citation

Park, Chul-Kyu, et al. "Extracellular microRNAs Activate Nociceptor Neurons to Elicit Pain Via TLR7 and TRPA1." Neuron, vol. 82, no. 1, 2014, pp. 47-54.
Park CK, Xu ZZ, Berta T, et al. Extracellular microRNAs activate nociceptor neurons to elicit pain via TLR7 and TRPA1. Neuron. 2014;82(1):47-54.
Park, C. K., Xu, Z. Z., Berta, T., Han, Q., Chen, G., Liu, X. J., & Ji, R. R. (2014). Extracellular microRNAs activate nociceptor neurons to elicit pain via TLR7 and TRPA1. Neuron, 82(1), 47-54. https://doi.org/10.1016/j.neuron.2014.02.011
Park CK, et al. Extracellular microRNAs Activate Nociceptor Neurons to Elicit Pain Via TLR7 and TRPA1. Neuron. 2014 Apr 2;82(1):47-54. PubMed PMID: 24698267.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extracellular microRNAs activate nociceptor neurons to elicit pain via TLR7 and TRPA1. AU - Park,Chul-Kyu, AU - Xu,Zhen-Zhong, AU - Berta,Temugin, AU - Han,Qingjian, AU - Chen,Gang, AU - Liu,Xing-Jun, AU - Ji,Ru-Rong, PY - 2014/01/28/accepted PY - 2014/4/5/entrez PY - 2014/4/5/pubmed PY - 2014/6/3/medline SP - 47 EP - 54 JF - Neuron JO - Neuron VL - 82 IS - 1 N2 - Intracellular microRNAs (miRNAs) are key regulators of gene expression. The role of extracellular miRNAs in neuronal activation and sensory behaviors are unknown. Here we report an unconventional role of extracellular miRNAs for rapid excitation of nociceptor neurons via toll-like receptor-7 (TLR7) and its coupling to TRPA1 ion channel. miRNA-let-7b induces rapid inward currents and action potentials in dorsal root ganglion (DRG) neurons. These responses require the GUUGUGU motif, only occur in neurons coexpressing TLR7 and TRPA1, and are abolished in mice lacking Tlr7 or Trpa1. Furthermore, let-7b induces TLR7/TRPA1-dependent single-channel activities in DRG neurons and HEK293 cells overexpressing TLR7/TRPA1. Intraplantar injection of let-7b elicits rapid spontaneous pain via TLR7 and TRPA1. Finally, let-7b can be released from DRG neurons by neuronal activation, and let-7b inhibitor reduces formalin-induced TRPA1 currents and spontaneous pain. Thus, secreted extracellular miRNAs may serve as novel pain mediators via activating TLR7/TRPA1 in nociceptor neurons. SN - 1097-4199 UR - https://www.unboundmedicine.com/medline/citation/24698267/Extracellular_microRNAs_activate_nociceptor_neurons_to_elicit_pain_via_TLR7_and_TRPA1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0896-6273(14)00109-3 DB - PRIME DP - Unbound Medicine ER -