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PAIN MEDICINE

A Prostaglandin E₂ Receptor Subtype EP₁ Receptor Antagonist (ONO-8711) Reduces Hyperalgesia, Allodynia, and C-fos Gene Expression in Rats with Chronic Nerve Constriction

Hiroyasu Kawahara, MD^*, Atsuhiro Sakamoto, MD PhD^*, Shinhiro Takeda, MD PhD^*, Hidetaka Onodera, MD PhD^*, Junko Imaki, MD PhD, and Ryo Ogawa, MD PhD^*

*Department of Anesthesiology, Depertment of Anatomy, Nippon Medical School, 1-1-5, Sendagi, Bunkyoku, Tokyo, Japan

Address correspondence and reprint requests to Hiroyasu Kawahara, MD, Department of Anesthesiology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan. Address e-mail to kawahara_hiroyasu/anesth{at}nms.ac.jp

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.

IMPLICATIONS: 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 hyperalgasia, allodynia, and c-fos positive cells. These findings suggested that EP₁ receptor antagonists may have a role in treatment of neuropathic pain.

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