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ATP-sensitive potassium channels alleviate postoperative pain through JNK-dependent MCP-1 expression in spinal cord.

Zhu X, Liu J, Gao Y, Cao S, Shen S - Int. J. Mol. Med. (2015)

Bottom Line: The results showed that KATP channel subunits Kir6.1, SUR1 and SUR2 were normally expressed in the spinal cord and significantly downregulated after SMIR.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.

ABSTRACT
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.

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KATP subunit expression after LPS incubation in astrocytes. *P≤0.05, **P≤0.01 vs. con. KATP, adenosine triphosphate-sensitive potassium.
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f5-ijmm-35-05-1257: KATP subunit expression after LPS incubation in astrocytes. *P≤0.05, **P≤0.01 vs. con. KATP, adenosine triphosphate-sensitive potassium.

Mentions: As Kir6.1, SUR2 and MCP-1 are expressed in astrocytes, we determined the interaction of KATP and MCP-1 in vitro, and prepared primary astrocytes from cerebral cortexes of neonatal rats. Since astrocytes were known to be activated by inflammatory mediators, we simulated astrocyte activation in vitro with LPS, a critical trigger, for inflammatory responses (15). As shown in Fig. 5C, after incubation with LPS (1 μg/ml) for 3 h, astrocytic MCP-1 expression was markedly increased (P<0.01) compared with the control group. By contrast, Kir6.1 and SUR2 expression was significantly decreased when astrocytes were exposed to LPS for 3 and 6 h, respectively (Fig. 5A and 5B).


ATP-sensitive potassium channels alleviate postoperative pain through JNK-dependent MCP-1 expression in spinal cord.

Zhu X, Liu J, Gao Y, Cao S, Shen S - Int. J. Mol. Med. (2015)

KATP subunit expression after LPS incubation in astrocytes. *P≤0.05, **P≤0.01 vs. con. KATP, adenosine triphosphate-sensitive potassium.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4380206&req=5

f5-ijmm-35-05-1257: KATP subunit expression after LPS incubation in astrocytes. *P≤0.05, **P≤0.01 vs. con. KATP, adenosine triphosphate-sensitive potassium.
Mentions: As Kir6.1, SUR2 and MCP-1 are expressed in astrocytes, we determined the interaction of KATP and MCP-1 in vitro, and prepared primary astrocytes from cerebral cortexes of neonatal rats. Since astrocytes were known to be activated by inflammatory mediators, we simulated astrocyte activation in vitro with LPS, a critical trigger, for inflammatory responses (15). As shown in Fig. 5C, after incubation with LPS (1 μg/ml) for 3 h, astrocytic MCP-1 expression was markedly increased (P<0.01) compared with the control group. By contrast, Kir6.1 and SUR2 expression was significantly decreased when astrocytes were exposed to LPS for 3 and 6 h, respectively (Fig. 5A and 5B).

Bottom Line: The results showed that KATP channel subunits Kir6.1, SUR1 and SUR2 were normally expressed in the spinal cord and significantly downregulated after SMIR.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus