PMID- 25812598
OWN - NLM
STAT- MEDLINE
DCOM- 20151217
LR  - 20181113
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 35
IP  - 5
DP  - 2015 May
TI  - ATP-sensitive potassium channels alleviate postoperative pain through 
      JNK-dependent MCP-1 expression in spinal cord.
PG  - 1257-65
LID - 10.3892/ijmm.2015.2143 [doi]
AB  - Although adenosine triphosphate-sensitive potassium (KATP) channels have been 
      proven to be involved in regulating postoperative pain, the underlying mechanism 
      remains to be investigated. In this study, we aimed to determine the role of 
      spinal KATP channels in the control of mechanical hypersensitivity in a rat pain 
      model, in which rats were subjected to skin/muscle incision and retraction (SMIR) 
      surgery, as well as in LPS-stimulated astrocytes. The results showed that KATP 
      channel subunits Kir6.1, SUR1 and SUR2 were normally expressed in the spinal cord 
      and significantly downregulated after SMIR. SMIR caused a marked increase in 
      monocyte chemoattractant protein-1 (MCP-1) mRNA expression and in the protein 
      level of p-JNK in the spinal cord. Intrathecal administration of a KATP channel 
      opener pinacidil (Pina) suppressed mechanical allodynia after SMIR and 
      significantly downregulated the MCP-1 mRNA expression and the protein level of 
      p-JNK induced by SMIR. Inverted fluorescence microscopy showed that Kir6.1 was 
      co-localized with astrocytes only and SUR2 was co-localized primarily with 
      neurons, in a small amount with astrocytes. Furthermore, in vitro studies showed 
      that following incubation with LPS, the astrocytic MCP-1 mRNA expression and 
      p-JNK content were markedly increased, whereas the mRNA levels of Kir6.1 and SUR2 
      were significantly downregulated in astrocytes. KATP channel opener pinacidil 
      inhibited the LPS-triggered MCP-1 and p-JNK elevation in rat primary astrocytes. 
      The results suggested that KATP channel opener treatment is an effective therapy 
      for postoperative pain in animals, through the activation of the JNK/MCP-1 
      pathway in astrocytes.
FAU - Zhu, Xiang
AU  - Zhu X
AD  - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 
      Jiangsu 226001, P.R. China.
FAU - Liu, Jinqian
AU  - Liu J
AD  - Department of Anesthesiology, Binzhou Medical University Hospital, Binzhou, 
      Shandong 256603, P.R. China.
FAU - Gao, Yongjing
AU  - Gao Y
AD  - Institute of Nautical Medicine, Nantong University, Nantong, Jiangsu 226001, P.R. 
      China.
FAU - Cao, Su
AU  - Cao S
AD  - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 
      Jiangsu 226001, P.R. China.
FAU - Shen, Shiren
AU  - Shen S
AD  - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 
      Jiangsu 226001, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150317
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Abcc9 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (KATP Channels)
RN  - 0 (Sulfonylurea Receptors)
RN  - 0 (uK-ATP-1 potassium channel)
RN  - 7B0ZZH8P2W (Pinacidil)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/metabolism
MH  - Chemokine CCL2/*genetics
MH  - Disease Models, Animal
MH  - Enzyme Activation
MH  - *Gene Expression Regulation/drug effects
MH  - Injections, Spinal
MH  - JNK Mitogen-Activated Protein Kinases/*metabolism
MH  - KATP Channels/agonists/*metabolism
MH  - Male
MH  - Pain Measurement
MH  - Pain Threshold
MH  - Pain, Postoperative/diagnosis/drug therapy/*genetics/*metabolism
MH  - Pinacidil/administration & dosage
MH  - Protein Transport
MH  - Rats
MH  - Spinal Cord/drug effects/*metabolism
MH  - Sulfonylurea Receptors/metabolism
PMC - PMC4380206
EDAT- 2015/03/31 06:00
MHDA- 2015/12/19 06:00
PMCR- 2015/03/17
CRDT- 2015/03/28 06:00
PHST- 2014/07/25 00:00 [received]
PHST- 2015/03/09 00:00 [accepted]
PHST- 2015/03/28 06:00 [entrez]
PHST- 2015/03/31 06:00 [pubmed]
PHST- 2015/12/19 06:00 [medline]
PHST- 2015/03/17 00:00 [pmc-release]
AID - ijmm-35-05-1257 [pii]
AID - 10.3892/ijmm.2015.2143 [doi]
PST - ppublish
SO  - Int J Mol Med. 2015 May;35(5):1257-65. doi: 10.3892/ijmm.2015.2143. Epub 2015 Mar 
      17.