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Ethyl pyruvate attenuates formalin-induced inflammatory nociception by inhibiting neuronal ERK phosphorylation.

Lee MJ, Jang M, Jung HS, Kim SH, Cho IH - Mol Pain (2012)

Bottom Line: EP significantly decreased formalin-induced nociceptive behavior during phase II, the magnitude of paw edema, and the activation of c-Fos in L4-L5 spinal dorsal horn.Interestingly, the i.t. administration of PD98059, an ERK upstream kinase (MEK) inhibitor, completely blocked the formalin-induced inflammatory nociceptive responses.These results demonstrate that EP may effectively inhibit formalin-induced inflammatory nociception via the inhibition of neuronal ERK phosphorylation in the spinal dorsal horn, indicating its therapeutic potential in suppressing acute inflammatory pain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anatomy, College of Oriental Medicine, and Institute of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.

ABSTRACT

Background: Ethyl pyruvate (EP) possesses anti-inflammatory activity. However, the potential anti-nociceptive value of EP for the treatment of the inflammatory nociception is largely unknown. We investigated whether EP could have any anti-nociceptive effect on inflammatory pain, after systemic administration of EP (10, 50, and 100 mg/kg, i.p.), 1 hour before formalin (5%, 50 μl) injection into the plantar surface of the hind paws of rats.

Results: EP significantly decreased formalin-induced nociceptive behavior during phase II, the magnitude of paw edema, and the activation of c-Fos in L4-L5 spinal dorsal horn. EP also attenuated the phosphorylation of extracellular signal-regulated kinase (ERK) in the neurons of L4-L5 spinal dorsal horn after formalin injection. Interestingly, the i.t. administration of PD98059, an ERK upstream kinase (MEK) inhibitor, completely blocked the formalin-induced inflammatory nociceptive responses.

Conclusions: These results demonstrate that EP may effectively inhibit formalin-induced inflammatory nociception via the inhibition of neuronal ERK phosphorylation in the spinal dorsal horn, indicating its therapeutic potential in suppressing acute inflammatory pain.

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Related in: MedlinePlus

Representative photomicrographs showing p-ERK-IR in the spinal DH (L4-L5) of formalin-treated rats. (A-I) p-ERK-IR in the spinal DH of the saline-pretreated and formalin treated rats. The p-ERK-IR was found exclusively in spinal DH neurons (A-C), but not in microglia (D-F) or astrocytes (G-I). (J,K) Microglia (J) and astrocytes (K) in normal rat (salinepretreated and saline-treated). Scale bar = 50 μm.
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Figure 4: Representative photomicrographs showing p-ERK-IR in the spinal DH (L4-L5) of formalin-treated rats. (A-I) p-ERK-IR in the spinal DH of the saline-pretreated and formalin treated rats. The p-ERK-IR was found exclusively in spinal DH neurons (A-C), but not in microglia (D-F) or astrocytes (G-I). (J,K) Microglia (J) and astrocytes (K) in normal rat (salinepretreated and saline-treated). Scale bar = 50 μm.

Mentions: To investigate the nature of the p-ERK-IR cells, we examined whether the ERK 1/2 are activated in neurons, microglia, or astrocytes using a multiple immunofluorescence method. Interestingly, the p-ERK immunofluorescence in the spinal DH was found exclusively in neurons (83.1%; 103 p-ERK-IR and NeuN-IR neurons of 124 p-ERK-IR neurons) (Figures 4A-4C), but not clear in microglia or astrocytess (Figures 4D-4I). Also microglia and astrocytes were not sufficiently activated 36–40 minutes after formalin treatment (Figures 4E, 4H, 4J and 4K). These results suggest that EP attenuates the formalin-induced acute inflammatory nociception through the inhibition of neuronal ERK activation, but not glial ERK activation.


Ethyl pyruvate attenuates formalin-induced inflammatory nociception by inhibiting neuronal ERK phosphorylation.

Lee MJ, Jang M, Jung HS, Kim SH, Cho IH - Mol Pain (2012)

Representative photomicrographs showing p-ERK-IR in the spinal DH (L4-L5) of formalin-treated rats. (A-I) p-ERK-IR in the spinal DH of the saline-pretreated and formalin treated rats. The p-ERK-IR was found exclusively in spinal DH neurons (A-C), but not in microglia (D-F) or astrocytes (G-I). (J,K) Microglia (J) and astrocytes (K) in normal rat (salinepretreated and saline-treated). Scale bar = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472237&req=5

Figure 4: Representative photomicrographs showing p-ERK-IR in the spinal DH (L4-L5) of formalin-treated rats. (A-I) p-ERK-IR in the spinal DH of the saline-pretreated and formalin treated rats. The p-ERK-IR was found exclusively in spinal DH neurons (A-C), but not in microglia (D-F) or astrocytes (G-I). (J,K) Microglia (J) and astrocytes (K) in normal rat (salinepretreated and saline-treated). Scale bar = 50 μm.
Mentions: To investigate the nature of the p-ERK-IR cells, we examined whether the ERK 1/2 are activated in neurons, microglia, or astrocytes using a multiple immunofluorescence method. Interestingly, the p-ERK immunofluorescence in the spinal DH was found exclusively in neurons (83.1%; 103 p-ERK-IR and NeuN-IR neurons of 124 p-ERK-IR neurons) (Figures 4A-4C), but not clear in microglia or astrocytess (Figures 4D-4I). Also microglia and astrocytes were not sufficiently activated 36–40 minutes after formalin treatment (Figures 4E, 4H, 4J and 4K). These results suggest that EP attenuates the formalin-induced acute inflammatory nociception through the inhibition of neuronal ERK activation, but not glial ERK activation.

Bottom Line: EP significantly decreased formalin-induced nociceptive behavior during phase II, the magnitude of paw edema, and the activation of c-Fos in L4-L5 spinal dorsal horn.Interestingly, the i.t. administration of PD98059, an ERK upstream kinase (MEK) inhibitor, completely blocked the formalin-induced inflammatory nociceptive responses.These results demonstrate that EP may effectively inhibit formalin-induced inflammatory nociception via the inhibition of neuronal ERK phosphorylation in the spinal dorsal horn, indicating its therapeutic potential in suppressing acute inflammatory pain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anatomy, College of Oriental Medicine, and Institute of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.

ABSTRACT

Background: Ethyl pyruvate (EP) possesses anti-inflammatory activity. However, the potential anti-nociceptive value of EP for the treatment of the inflammatory nociception is largely unknown. We investigated whether EP could have any anti-nociceptive effect on inflammatory pain, after systemic administration of EP (10, 50, and 100 mg/kg, i.p.), 1 hour before formalin (5%, 50 μl) injection into the plantar surface of the hind paws of rats.

Results: EP significantly decreased formalin-induced nociceptive behavior during phase II, the magnitude of paw edema, and the activation of c-Fos in L4-L5 spinal dorsal horn. EP also attenuated the phosphorylation of extracellular signal-regulated kinase (ERK) in the neurons of L4-L5 spinal dorsal horn after formalin injection. Interestingly, the i.t. administration of PD98059, an ERK upstream kinase (MEK) inhibitor, completely blocked the formalin-induced inflammatory nociceptive responses.

Conclusions: These results demonstrate that EP may effectively inhibit formalin-induced inflammatory nociception via the inhibition of neuronal ERK phosphorylation in the spinal dorsal horn, indicating its therapeutic potential in suppressing acute inflammatory pain.

Show MeSH
Related in: MedlinePlus