A prostaglandin E2 receptor subtype EP1 receptor antagonist (ONO-8711) reduces hyperalgesia, allodynia, and c-fos gene expression in rats with chronic nerve constriction.
Chronic constriction injury (CCI) of the sciatic nerve in rats induces persistent mechanical hyperalgesia and allodynia. CCI is widely known as a model of neuropathic pain, and many studies using this model have been reported. Recently, c-fos has been used as a neural marker of pain, and various studies have assessed the relationship between hyperalgesia and c-fos expression in the lumbar spinal cord. In this study, we examined the role of a prostaglandin E2 receptor subtype EP1 receptor antagonist (ONO-8711) in a rat CCI model. EP1 receptor antagonist (EP1-ra) oral administration from day 8 to day 14 significantly reduced hyperalgesia and allodynia in the three pain tests on day 15. EP1-ra treatment from day 8 to 14 also reduced c-fos-positive cells in laminae I-II, III-IV, and V-X compared with saline treatment. A single dose of EP1-ra treatment on day 8 significantly reduced hyperalgesia and allodynia at 1 h and 2 h after administration, but the efficacy was not observed at 24 h. We conclude that EP1-ra treatment may be useful for hyperalgesia and allodynia and that EP1 receptor mechanisms are involved in the maintenance of c-fos gene expression induced by nerve injury.


CONCLUSIONS
We examined whether a prostaglandin E2 receptor subtype EP1 receptor antagonist abrogates neuropathic pain induced by chronic constriction injury model in rats. The EP1 receptor antagonist significantly reduced hyperalgesia, allodynia, and c-fos positive cells. These findings suggested that EP1 receptor antagonists may have a role in treatment of neuropathic pain.
Kawahara
H
H
Department of Anesthesiology, Nippon Medical School, 1-1-5, Sendagi, Bunkyoku, Tokyo, Japan. kawahara_hiroyasu/anesth@nms.ac.jp
Sakamoto
A
A
Takeda
S
S
Onodera
H
H
Imaki
J
J
Ogawa
R
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002208:Caproates / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy*; D008026:Ligation; D008297:Male; D010147:Pain Measurement / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D012584:Sciatic Nerve / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001643:Bridged Bicyclo Compounds; D002208:Caproates; C122148:ONO 8711; C545637:Ptger1 protein, rat; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D004008:Diclofenac