Participation of D-serine and NR2 subunits in EphA4-mediated trigeminal neuropathic pain
10.11620/IJOB.2020.45.3.84
- Author:
Myung-Dong KIM
1
;
Min-Ji KIM
;
Jo-Young SON
;
Yu-Mi KIM
;
Jin-Sook JU
;
Dong-Kuk AHN
Author Information
1. Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu 41940, Republic of Korea
- Publication Type:Original Article
- From:International Journal of Oral Biology
2020;45(3):84-91
- CountryRepublic of Korea
- Language:Korean
-
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.