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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

Schematic drawing representing the experimental protocol used for inflammatory pain with formalin, ethyl pyruvate (EP) and PD-98059 treatments. IHC, immunohistochemistry; WB, Western blots; i.pl., intraplanter; i.p., intraperitoneal.
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Figure 7: Schematic drawing representing the experimental protocol used for inflammatory pain with formalin, ethyl pyruvate (EP) and PD-98059 treatments. IHC, immunohistochemistry; WB, Western blots; i.pl., intraplanter; i.p., intraperitoneal.

Mentions: The formalin-induced nociceptive response was tested as described previously [28]. Briefly male SD rats were randomly assigned to two groups; saline-treated control group (n = 15), and EP-treated experimental group (n = 37). Three EP-treated group received EP (Sigma-Aldrich, USA) at doses of 10 mg/kg (n = 14), 50 mg/kg (n = 10) or 100 mg/kg (n = 13) intraperitoneally 1 hour before formalin injection, respectively (Figure 7A). Control rats received an equal volume of saline vehicle. The dosage of EP was determined based on doses used in previous reports of the therapeutic effects of EP [9,12,62]. The time point of formalin injection was determined based on a previous report of the optimal delivery of EP in rats [9,12,62]. Following intraplantar injection of formalin (5%, 50 μl) into the right hind paw, rats were placed in a clear plastic cage (20 × 26 × 12 cm) without bedding, and the total time of pain responses, licking/rubbing on the injected area or lifting the paw, was counted in 5 minutes interval for 60 minutes. The behavioral tests were performed blinded under the constant condition (temperature, 23 ± 3°C; humidity, 55 ± 5%) between 9:00 am and 12:00 am in a quiet room.


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)

Schematic drawing representing the experimental protocol used for inflammatory pain with formalin, ethyl pyruvate (EP) and PD-98059 treatments. IHC, immunohistochemistry; WB, Western blots; i.pl., intraplanter; i.p., intraperitoneal.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Schematic drawing representing the experimental protocol used for inflammatory pain with formalin, ethyl pyruvate (EP) and PD-98059 treatments. IHC, immunohistochemistry; WB, Western blots; i.pl., intraplanter; i.p., intraperitoneal.
Mentions: The formalin-induced nociceptive response was tested as described previously [28]. Briefly male SD rats were randomly assigned to two groups; saline-treated control group (n = 15), and EP-treated experimental group (n = 37). Three EP-treated group received EP (Sigma-Aldrich, USA) at doses of 10 mg/kg (n = 14), 50 mg/kg (n = 10) or 100 mg/kg (n = 13) intraperitoneally 1 hour before formalin injection, respectively (Figure 7A). Control rats received an equal volume of saline vehicle. The dosage of EP was determined based on doses used in previous reports of the therapeutic effects of EP [9,12,62]. The time point of formalin injection was determined based on a previous report of the optimal delivery of EP in rats [9,12,62]. Following intraplantar injection of formalin (5%, 50 μl) into the right hind paw, rats were placed in a clear plastic cage (20 × 26 × 12 cm) without bedding, and the total time of pain responses, licking/rubbing on the injected area or lifting the paw, was counted in 5 minutes interval for 60 minutes. The behavioral tests were performed blinded under the constant condition (temperature, 23 ± 3°C; humidity, 55 ± 5%) between 9:00 am and 12:00 am in a quiet room.

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