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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

Photomicrographs showing changes in CD11/b-IR in the spinal DH (L4-L5) 3 days after formalin injection. Inhibitory effects of EP on microglial activation were clear at 3 days following formalin injection. Insets are high magnification of the open rectangles. (A) Contralateral spinal DH of saline-pretreated and formalin-treated rats. (B) Ipsilateral spinal DH of saline-pretreated and formalin-treated rats. (C) Ipsilateral spinal DH of EP-pretreated and formalin-treated rats. Scale bar = 50 μm. (D) The Iba-1-IR intensity was measured as the average pixel intensity per 0.5 mm2 area within medial portion of the L4-L5 spinal DH at 3 days after formalin injection. The Iba-1-IR intensity was significantly increased by formalin injection, however this increased intensity significantly decreased by EP. Values are expressed as mean ± SEM. *P < 0.01 vs. normal rats (saline-pretreated and saline-treated) or control rats (saline-pretreated and formalin-treated).
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Figure 5: Photomicrographs showing changes in CD11/b-IR in the spinal DH (L4-L5) 3 days after formalin injection. Inhibitory effects of EP on microglial activation were clear at 3 days following formalin injection. Insets are high magnification of the open rectangles. (A) Contralateral spinal DH of saline-pretreated and formalin-treated rats. (B) Ipsilateral spinal DH of saline-pretreated and formalin-treated rats. (C) Ipsilateral spinal DH of EP-pretreated and formalin-treated rats. Scale bar = 50 μm. (D) The Iba-1-IR intensity was measured as the average pixel intensity per 0.5 mm2 area within medial portion of the L4-L5 spinal DH at 3 days after formalin injection. The Iba-1-IR intensity was significantly increased by formalin injection, however this increased intensity significantly decreased by EP. Values are expressed as mean ± SEM. *P < 0.01 vs. normal rats (saline-pretreated and saline-treated) or control rats (saline-pretreated and formalin-treated).

Mentions: To examine whether the EP could inhibit microglial activation in our formalin-induced inflammatory nociception model, we administrated EP (100 mg/kg, i.p.) to formalin-injected rats once daily for 3 days. When we analyzed Iba-1-IR in spinal DH 3 days following formalin injection, microglia was clearly activated by formalin intraplantar injection compared to that of saline-treated rats. However, this microglial activation was remarkably inhibited by EP administration (Figures 5A-5D). These results confirmed that spinal microglia was not affected in cell morphology by either formalin or EP during phase II of the formalin-induced pain model, and that spinal microglia do not contribute to acute inflammatory pain.


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)

Photomicrographs showing changes in CD11/b-IR in the spinal DH (L4-L5) 3 days after formalin injection. Inhibitory effects of EP on microglial activation were clear at 3 days following formalin injection. Insets are high magnification of the open rectangles. (A) Contralateral spinal DH of saline-pretreated and formalin-treated rats. (B) Ipsilateral spinal DH of saline-pretreated and formalin-treated rats. (C) Ipsilateral spinal DH of EP-pretreated and formalin-treated rats. Scale bar = 50 μm. (D) The Iba-1-IR intensity was measured as the average pixel intensity per 0.5 mm2 area within medial portion of the L4-L5 spinal DH at 3 days after formalin injection. The Iba-1-IR intensity was significantly increased by formalin injection, however this increased intensity significantly decreased by EP. Values are expressed as mean ± SEM. *P < 0.01 vs. normal rats (saline-pretreated and saline-treated) or control rats (saline-pretreated and formalin-treated).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Photomicrographs showing changes in CD11/b-IR in the spinal DH (L4-L5) 3 days after formalin injection. Inhibitory effects of EP on microglial activation were clear at 3 days following formalin injection. Insets are high magnification of the open rectangles. (A) Contralateral spinal DH of saline-pretreated and formalin-treated rats. (B) Ipsilateral spinal DH of saline-pretreated and formalin-treated rats. (C) Ipsilateral spinal DH of EP-pretreated and formalin-treated rats. Scale bar = 50 μm. (D) The Iba-1-IR intensity was measured as the average pixel intensity per 0.5 mm2 area within medial portion of the L4-L5 spinal DH at 3 days after formalin injection. The Iba-1-IR intensity was significantly increased by formalin injection, however this increased intensity significantly decreased by EP. Values are expressed as mean ± SEM. *P < 0.01 vs. normal rats (saline-pretreated and saline-treated) or control rats (saline-pretreated and formalin-treated).
Mentions: To examine whether the EP could inhibit microglial activation in our formalin-induced inflammatory nociception model, we administrated EP (100 mg/kg, i.p.) to formalin-injected rats once daily for 3 days. When we analyzed Iba-1-IR in spinal DH 3 days following formalin injection, microglia was clearly activated by formalin intraplantar injection compared to that of saline-treated rats. However, this microglial activation was remarkably inhibited by EP administration (Figures 5A-5D). These results confirmed that spinal microglia was not affected in cell morphology by either formalin or EP during phase II of the formalin-induced pain model, and that spinal microglia do not contribute to acute inflammatory pain.

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