The present study investigated the participation of D-serine and NR2 in antinociception produced by blockade of central erythropoietin-producing hepatocellular carcinoma (Eph) A4 (EphA4) signaling in rats with trigeminal neuropathic pain. Trigeminal neuropathic pain was modeled in male Sprague-Dawley rats using mal-positioned dental implants. The left mandibular second molar was extracted under anesthesia, and a miniature dental implant was placed to induce injury to the inferior alveolar nerve. Our current findings showed that nerve injury induced by malpositioned dental implants significantly produced mechanical allodynia; additionally, the inferior alveolar nerve injury increased the expression of D-serine and NR2 subunits in the ipsilateral medullary dorsal horn (trigeminal subnucleus caudalis). Intracisternal administration of EphA4-Fc, an EphA4 inhibitor, inhibited nerve injury-induced mechanical allodynia and upregulated the expression of D-serine and NR2 subunits. Moreover, intracisternal administration of D-amino acids oxidase, a D-serine inhibitor, inhibited trigeminal mechanical allodynia. These results show that D-serine and NR2 subunit pathways participate in central EphA4 signaling after an inferior alveolar nerve injury. Therefore, blockade of D-serine and NR2 subunit pathways in central EphA4 signaling provides a new therapeutic target for the treatment of trigeminal neuropathic pain.

Introduction
Materials and Methods
    1. 실험동물
    2. 악안면 신경병성통증 동물모델
    3. 소뇌연수조 내 약물주입
    4. 안면 이질통증의 평가
    5. 면역조직화학염색
    6. 통계분석
Results
Discussion
References

• Myung-Dong Kim(Department of Oral Physiology, School of Dentistry, Kyungpook National University)
• Min-Ji Kim(Department of Oral Physiology, School of Dentistry, Kyungpook National University)
• Jo-Young Son(Department of Oral Physiology, School of Dentistry, Kyungpook National University)
• Yu-Mi Kim(Department of Oral Physiology, School of Dentistry, Kyungpook National University)
• Jin-Sook Ju(Department of Oral Physiology, School of Dentistry, Kyungpook National University)
• Dong-Kuk Ahn(Department of Oral Physiology, School of Dentistry, Kyungpook National University) Correspondence to