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

Mol Pain. 2012 May 28;8:40. doi: 10.1186/1744-8069-8-40.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11 Antigens / metabolism
  • Cell Shape / drug effects
  • Edema / chemically induced
  • Edema / complications
  • Edema / drug therapy
  • Edema / pathology
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Flavonoids / administration & dosage
  • Flavonoids / pharmacology
  • Formaldehyde
  • Inflammation / drug therapy*
  • Inflammation / enzymology*
  • Inflammation / pathology
  • Injections, Spinal
  • Male
  • Microglia / drug effects
  • Microglia / metabolism
  • Microglia / pathology
  • Neurons / drug effects
  • Neurons / enzymology*
  • Neurons / pathology
  • Nociception / drug effects*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-fos / metabolism
  • Pyruvates / administration & dosage
  • Pyruvates / pharmacology*
  • Pyruvates / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Spinal Cord / pathology

Substances

  • CD11 Antigens
  • Flavonoids
  • Proto-Oncogene Proteins c-fos
  • Pyruvates
  • ethyl pyruvate
  • Formaldehyde
  • Extracellular Signal-Regulated MAP Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one