Participation of D-serine and NR2 subunits in EphA4-mediated trigeminal neuropathic pain
김명동, 김민지, 손조영, 김유미, 주진숙, 안동국,
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김명동 ( Kim Myung-Dong ) - Kyungpook National University School of Dentistry Department of Oral Physiology
김민지 ( Kim Min-Ji ) - Kyungpook National University School of Dentistry Department of Oral Physiology
손조영 ( Son Jo-Young ) - Kyungpook National University School of Dentistry Department of Oral Physiology
김유미 ( Kim Yu-Mi ) - Kyungpook National University School of Dentistry Department of Oral Physiology
주진숙 ( Ju Jin-Sook ) - Kyungpook National University School of Dentistry Department of Oral Physiology
안동국 ( Ahn Dong-Kuk ) - Kyungpook National University School of Dentistry Department of Oral Physiology
Abstract
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.
키워드
Ephrin-A4; D-serine; NR2 subunits; Trigeminal; Neuropathic pain
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