Ethyl pyruvate attenuates formalin-induced inflammatory nociception by inhibiting neuronal ERK phosphorylation.
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.
Department of Anatomy, College of Oriental Medicine, and Institute of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
Min Jung
MJ
Lee
Minhee
M
Jang
Hyuk-Sang
HS
Jung
Sung-Hoon
SH
Kim
Ik-Hyun
IH
Cho
D000818:Animals; D018845:CD11 Antigens / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology; D005557:Formaldehyde; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D007278:Injections, Spinal; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D059225:Nociception / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011773:Pyruvates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D018845:CD11 Antigens; D005419:Flavonoids; D016760:Proto-Oncogene Proteins c-fos; D011773:Pyruvates; C046522:ethyl pyruvate; D005557:Formaldehyde; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one