PMID- 27038234
OWN - NLM
STAT- MEDLINE
DCOM- 20171113
LR  - 20231213
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Linking)
VI  - 43
IP  - 11
DP  - 2016 Jun
TI  - Intrathecal administration of low-dose nociceptin/orphanin FQ induces allodynia 
      via c-Jun N-terminal kinase and monocyte chemoattractant protein-1.
PG  - 1499-508
LID - 10.1111/ejn.13247 [doi]
AB  - Pathological chronic pain, which is frequently associated with prolonged tissue 
      damage, inflammation, tumour invasion, and neurodegenerative diseases, gives rise 
      to hyperalgesia and allodynia. We previously reported that intrathecal 
      administration of nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for the 
      orphan opioid receptor-like receptor, in the femtomole range induces touch-evoked 
      allodynia. N/OFQ has been implicated in multiple signalling pathways, such as 
      inhibition of cAMP production and Ca(2+) channels, or activation of K(+) channels 
      and mitogen-activated protein kinase, although the signalling pathways of 
      N/OFQ-induced allodynia remain unclear. To address these issues, we developed an 
      ex vivo mitogen-activated protein kinase assay by using intact slices of mouse 
      spinal cord. N/OFQ markedly increased the phosphorylation of c-Jun N-terminal 
      kinase (JNK) in the superficial dorsal horn of the spinal cord. The 
      N/OFQ-stimulated JNK phosphorylation was significantly inhibited by pertussis 
      toxin, the phospholipase C inhibitor U73122, and the inositol trisphosphate 
      receptor antagonist Xestospongin C. Intrathecal administration of the JNK 
      inhibitor SP600125 inhibited N/OFQ-evoked allodynia. The N/OFQ-induced increase 
      in JNK phosphorylation was observed in astrocytes that expressed glial fibrillary 
      acidic protein. N/OFQ also induced monocyte chemoattractant protein-1 (MCP-1) 
      release via the JNK pathway, and N/OFQ-induced JNK phosphorylation was observed 
      in MCP-1-immunoreactive astrocytes. Intrathecal administration of the MCP-1 
      receptor antagonist RS504393 inhibited N/OFQ-evoked allodynia. These results 
      suggest that, in the spinal dorsal horn, N/OFQ induces allodynia through 
      activation of JNK via the phospholipase C-inositol trisphosphate pathway, which 
      is coupled to pertussis toxin-sensitive G-protein, and following the release of 
      MCP-1 from astrocytes.
CI  - (c) 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
FAU - Kawabata, Kenta
AU  - Kawabata K
AD  - Department of Biomedical Engineering, Osaka Institute of Technology, 5-16-1 
      Omiya, Asahi-ku, Osaka, 535-8585, Japan.
FAU - Nishimura, Isamu
AU  - Nishimura I
AD  - Department of Biomedical Engineering, Osaka Institute of Technology, 5-16-1 
      Omiya, Asahi-ku, Osaka, 535-8585, Japan.
FAU - Fujiwara, Takeshi
AU  - Fujiwara T
AD  - Department of Biomedical Engineering, Osaka Institute of Technology, 5-16-1 
      Omiya, Asahi-ku, Osaka, 535-8585, Japan.
FAU - Terauchi, Shoko
AU  - Terauchi S
AD  - Department of Biomedical Engineering, Osaka Institute of Technology, 5-16-1 
      Omiya, Asahi-ku, Osaka, 535-8585, Japan.
FAU - Minami, Toshiaki
AU  - Minami T
AD  - Department of Anaesthesiology, Osaka Medical College, Takatsuki, Japan.
FAU - Ito, Seiji
AU  - Ito S
AD  - Department of Medical Chemistry, Kansai Medical University, Hirakata, Japan.
FAU - Okuda-Ashitaka, Emiko
AU  - Okuda-Ashitaka E
AD  - Department of Biomedical Engineering, Osaka Institute of Technology, 5-16-1 
      Omiya, Asahi-ku, Osaka, 535-8585, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160505
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Chemokine CCL2)
RN  - 0 (Opioid Peptides)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Chemokine CCL2/*metabolism
MH  - Hyperalgesia/chemically induced/*metabolism
MH  - Injections, Spinal
MH  - JNK Mitogen-Activated Protein Kinases/*metabolism
MH  - Mice
MH  - Opioid Peptides/*administration & dosage
MH  - Phosphorylation
MH  - Signal Transduction
MH  - Spinal Cord/*metabolism
MH  - Nociceptin
OTO - NOTNLM
OT  - astrocyte
OT  - inositol trisphosphate
OT  - pertussis toxin-sensitive G-protein
OT  - phospholipase C
EDAT- 2016/04/03 06:00
MHDA- 2017/11/14 06:00
CRDT- 2016/04/03 06:00
PHST- 2015/11/25 00:00 [received]
PHST- 2016/03/11 00:00 [revised]
PHST- 2016/03/29 00:00 [accepted]
PHST- 2016/04/03 06:00 [entrez]
PHST- 2016/04/03 06:00 [pubmed]
PHST- 2017/11/14 06:00 [medline]
AID - 10.1111/ejn.13247 [doi]
PST - ppublish
SO  - Eur J Neurosci. 2016 Jun;43(11):1499-508. doi: 10.1111/ejn.13247. Epub 2016 May 
      5.