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Participation of D-serine and NR2 subunits in EphA4-mediated trigeminal neuropathic pain

  • Kim, Myung-Dong (Department of Oral Physiology, School of Dentistry, Kyungpook National University) ;
  • Kim, Min-Ji (Department of Oral Physiology, School of Dentistry, Kyungpook National University) ;
  • Son, Jo-Young (Department of Oral Physiology, School of Dentistry, Kyungpook National University) ;
  • Kim, Yu-Mi (Department of Oral Physiology, School of Dentistry, Kyungpook National University) ;
  • Ju, Jin-Sook (Department of Oral Physiology, School of Dentistry, Kyungpook National University) ;
  • Ahn, Dong-Kuk (Department of Oral Physiology, School of Dentistry, Kyungpook National University)
  • 투고 : 2020.05.19
  • 심사 : 2020.08.20
  • 발행 : 2020.09.30

초록

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

참고문헌

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