Intraplantar PGE2 causes nociceptive behaviour and mechanical allodynia: the role of prostanoid E receptors and protein kinases.
OBJECTIVE
Receptor subtypes involved in PGE(2)-induced nociception are still controversial. The present study investigated the prostanoid E receptor (EP) subtypes and the protein kinase (PK) pathways involved in the nociception induced by PGE(2) injection in the mouse paw.


METHODS
Paw-licking and mechanical allodynia were measured in vivo and protein kinase activation ex vivo by Western blots of extracts of paw skin.


RESULTS
Intraplantar (i.pl.) injection of PGE(2) into the mouse paw caused nociceptive behaviour of short duration with mean ED(50) of 1.43 nmol. PGE(2) produced a longer-lasting mechanical allodynia, with an ED(50) of 0.05 nmol. Intraplantar injection of antagonists at EP(3) or EP(4), but not at EP(1) or EP(2) receptors inhibited PGE(2)-induced paw-licking. Paw-licking caused by PGE(2) was blocked by an inhibitor of PKA but only partially decreased by inhibition of the extracellular-regulated kinase (ERK). Selective inhibitors of PKC, c-Jun N-terminal kinase (JNK) or p38, all failed to affect PGE(2)-induced paw-licking. An EP(3) antagonist inhibited PGE(2)-induced mechanical allodynia. However, inhibitors of PKA, PKC or ERK, but not p38 or JNK, also partially inhibited PGE(2)-induced mechanical allodynia. Western blot analyses confirmed that i.pl. injection of PGE(2) activated PKA, PKCalpha, and mitogen activated kinases (MAPKs) in the paw. Co-treatment with EP(3) or EP(4) receptor antagonists reduced PGE(2)-induced PKA and ERK, but not PKCalpha activation.


CONCLUSIONS
The present results indicate that the nociceptive behaviour and mechanical allodynia caused by i.pl. PGE(2) are mediated through activation of distinct EP receptors and PK-dependent mechanisms.
Kassuya
C A L
CA
Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
Ferreira
J
J
Claudino
R F
RF
Calixto
J B
JB
D000178:Acrylamides / Q000008:administration & dosage; D000818:Animals; D002351:Carrageenan / Q000008:administration & dosage; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015232:Dinoprostone / Q000008:administration & dosage* / Q000031:analogs & derivatives; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009281:Naphthalenes / Q000008:administration & dosage; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D010147:Pain Measurement; D011459:Prostaglandins E, Synthetic / Q000008:administration & dosage; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000145:classification / Q000502:physiology*; D013314:Stress, Mechanical
C092396:17-phenyltrinorprostaglandin E2; D000178:Acrylamides; C508710:L-826266; D009281:Naphthalenes; D011459:Prostaglandins E, Synthetic; D018078:Receptors, Prostaglandin E; D002351:Carrageenan; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone