PMID- 29343707
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20220318
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Jan 17
TI  - Sensory neuronal P2RX4 receptors controls BDNF signaling in inflammatory pain.
PG  - 964
LID - 10.1038/s41598-018-19301-5 [doi]
LID - 964
AB  - Chronic inflammatory and neuropathic pains are major public health concerns. 
      Potential therapeutic targets include the ATP-gated purinergic receptors (P2RX) 
      that contribute to these pathological types of pain in several different cell 
      types. The purinergic receptors P2RX2 and P2RX3 are expressed by a specific 
      subset of dorsal root ganglion neurons and directly shape pain processing by 
      primary afferents. In contrast the P2RX4 and P2RX7 are mostly expressed in 
      myeloid cells, where activation of these receptors triggers the release of 
      various pro-inflammatory molecules. Here, we demonstrate that P2RX4 also controls 
      calcium influx in mouse dorsal root ganglion neurons. P2RX4 is up-regulated in 
      pain-processing neurons during long lasting peripheral inflammation and it 
      co-localizes with Brain-Derived Neurotrophic Factor (BDNF). In the dorsal horn of 
      the spinal cord, BDNF-dependent signaling pathways, phosphorylation of Erk1/2 and 
      of the GluN1 subunit as well as the down regulation of the co-transporter KCC2, 
      which are triggered by peripheral inflammation are impaired in P2RX4-deficient 
      mice. Our results suggest that P2RX4, expressed by sensory neurons, controls 
      neuronal BDNF release that contributes to hyper-excitability during chronic 
      inflammatory pain and establish P2RX4 in sensory neurons as a new potential 
      therapeutic target to treat hyperexcitability during chronic inflammatory pain.
FAU - Lalisse, Sarah
AU  - Lalisse S
AD  - Institute of Functional Genomics, Universite de Montpellier, Unite Mixte de 
      Recherche, 5302 CNRS, 141 rue de la cardonille, F34094, Montpellier, France.
AD  - Unite de recherche U1191, INSERM, Montpellier, France.
AD  - LabEx Ion Channel Science and Therapeutics, 141 rue de la cardonille, 
      Montpellier, F34094, France.
FAU - Hua, Jennifer
AU  - Hua J
AD  - Institute of Functional Genomics, Universite de Montpellier, Unite Mixte de 
      Recherche, 5302 CNRS, 141 rue de la cardonille, F34094, Montpellier, France.
AD  - Unite de recherche U1191, INSERM, Montpellier, France.
AD  - LabEx Ion Channel Science and Therapeutics, 141 rue de la cardonille, 
      Montpellier, F34094, France.
FAU - Lenoir, Manon
AU  - Lenoir M
AD  - Institute of Functional Genomics, Universite de Montpellier, Unite Mixte de 
      Recherche, 5302 CNRS, 141 rue de la cardonille, F34094, Montpellier, France.
AD  - Unite de recherche U1191, INSERM, Montpellier, France.
AD  - LabEx Ion Channel Science and Therapeutics, 141 rue de la cardonille, 
      Montpellier, F34094, France.
FAU - Linck, Nathalie
AU  - Linck N
AD  - Institute of Functional Genomics, Universite de Montpellier, Unite Mixte de 
      Recherche, 5302 CNRS, 141 rue de la cardonille, F34094, Montpellier, France.
AD  - Unite de recherche U1191, INSERM, Montpellier, France.
AD  - LabEx Ion Channel Science and Therapeutics, 141 rue de la cardonille, 
      Montpellier, F34094, France.
FAU - Rassendren, Francois
AU  - Rassendren F
AUID- ORCID: 0000-0003-3320-2461
AD  - Institute of Functional Genomics, Universite de Montpellier, Unite Mixte de 
      Recherche, 5302 CNRS, 141 rue de la cardonille, F34094, Montpellier, France.
AD  - Unite de recherche U1191, INSERM, Montpellier, France.
AD  - LabEx Ion Channel Science and Therapeutics, 141 rue de la cardonille, 
      Montpellier, F34094, France.
FAU - Ulmann, Lauriane
AU  - Ulmann L
AD  - Institute of Functional Genomics, Universite de Montpellier, Unite Mixte de 
      Recherche, 5302 CNRS, 141 rue de la cardonille, F34094, Montpellier, France. 
      lauriane.ulmann@igf.cnrs.fr.
AD  - Unite de recherche U1191, INSERM, Montpellier, France. 
      lauriane.ulmann@igf.cnrs.fr.
AD  - LabEx Ion Channel Science and Therapeutics, 141 rue de la cardonille, 
      Montpellier, F34094, France. lauriane.ulmann@igf.cnrs.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180117
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (P2rx4 protein, mouse)
RN  - 0 (Receptors, Purinergic P2X4)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Female
MH  - Ganglia, Spinal/*metabolism
MH  - Hyperalgesia/metabolism
MH  - Inflammation/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuralgia/metabolism
MH  - Receptors, Purinergic P2X4/*metabolism
MH  - Sensory Receptor Cells/*metabolism
MH  - Signal Transduction/*physiology
MH  - Spinal Cord Dorsal Horn/metabolism
MH  - Up-Regulation/physiology
PMC - PMC5772667
COIS- The authors declare that they have no competing interests.
EDAT- 2018/01/19 06:00
MHDA- 2018/11/27 06:00
PMCR- 2018/01/17
CRDT- 2018/01/19 06:00
PHST- 2017/04/12 00:00 [received]
PHST- 2017/12/27 00:00 [accepted]
PHST- 2018/01/19 06:00 [entrez]
PHST- 2018/01/19 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
PHST- 2018/01/17 00:00 [pmc-release]
AID - 10.1038/s41598-018-19301-5 [pii]
AID - 19301 [pii]
AID - 10.1038/s41598-018-19301-5 [doi]
PST - epublish
SO  - Sci Rep. 2018 Jan 17;8(1):964. doi: 10.1038/s41598-018-19301-5.