Spinal miRNA-124 regulates synaptopodin and nociception in an animal model of bone cancer pain.
Sci Rep. 2017-09-08; 7(1):
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Elramah S(1)(2), López-González MJ(1)(2), Bastide M(1)(2), Dixmérias F(3), Roca-Lapirot O(1)(2), Wielanek-Bachelet AC(4), Vital A(5), Leste-Lasserre T(6), Brochard A(6), Landry M(1)(2), Favereaux A(7)(8).
(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.
(8)CNRS UMR 5297 « Central mechanisms of pain sensitization », Institut Interdisciplinaire de Neuroscience, 146 rue Léo Saignat, Bordeaux Cedex, 33077, France.
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.