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Sci Rep. 2017 Sep 8;7(1):10949. doi: 10.1038/s41598-017-10224-1.

Spinal miRNA-124 regulates synaptopodin and nociception in an animal model of bone cancer pain.

Author information

1
Bordeaux University, Bordeaux, France.
2
CNRS UMR 5297 « Central mechanisms of pain sensitization », Institut Interdisciplinaire de Neuroscience, 146 rue Léo Saignat, Bordeaux Cedex, 33077, France.
3
Department of Anesthesia and Pain, Institut Bergonié, Bordeaux, France.
4
Service de Neurologie Groupe hospitalier Sud Hôpital Haut-Lévêque, Avenue de Magellan, Pessac Cedex, 33604, France.
5
Univ. Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, F-33000, France.
6
INSERM U862 « Physiopathologie de l'addiction », Institut François Magendie, 146 rue Léo Saignat, Bordeaux Cedex, 33077, France.
7
Bordeaux University, Bordeaux, France. alexandre.favereaux@u-bordeaux.fr.
8
CNRS UMR 5297 « Central mechanisms of pain sensitization », Institut Interdisciplinaire de Neuroscience, 146 rue Léo Saignat, Bordeaux Cedex, 33077, France. alexandre.favereaux@u-bordeaux.fr.

Abstract

Strong breakthrough pain is one of the most disabling symptoms of cancer since it affects up to 90% of cancer patients and is often refractory to treatments. Alteration in gene expression is a known mechanism of cancer pain in which microRNAs (miRNAs), a class of non-coding regulatory RNAs, play a crucial role. Here, in a mouse model of cancer pain, we show that miR-124 is down-regulated in the spinal cord, the first relay of the pain signal to the brain. Using in vitro and in vivo approaches, we demonstrate that miR-124 is an endogenous and specific inhibitor of synaptopodin (Synpo), a key protein for synaptic transmission. In addition, we demonstrate that Synpo is a key component of the nociceptive pathways. Interestingly, miR-124 was down-regulated in the spinal cord in cancer pain conditions, leading to an up-regulation of Synpo. Furthermore, intrathecal injections of miR-124 mimics in cancerous mice normalized Synpo expression and completely alleviated cancer pain in the early phase of the cancer. Finally, miR-124 was also down-regulated in the cerebrospinal fluid of cancer patients who developed pain, suggesting that miR-124 could be an efficient analgesic drug to treat cancer pain patients.

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