Effects of D-Serine and MK-801 on Neuropathic Pain and Functional Recovery in a Rat Model of Spinal Cord Injury

초록

Objective: Neuropathic pain is a common secondary complication of spinal cord injury (SCI). N-methyl-D-aspartate (NMDA) receptor activation is critical for hypersensitivity in neuropathic pain. This activation requires the binding of both glutamate and the D-serine co-agonist to the NMDA glycine site. We evaluated the effects of D-serine on neuropathic pain after SCI and explored the underlying molecular mechanisms.Methods: Anesthetized rats underwent T9 spinal cord contusion (130 kdyn). D-serine (500 and 1,000 mg/kg) and MK-801 hydrogen maleate (2.0 mg/kg) were injected daily for 2 weeks, starting the day after SCI. Functional outcomes were assessed according to the Basso, Beat-tie, and Bresnahan scale, while histological outcomes were evaluated based on lesion vol-ume and spared tissue area. Mechanical allodynia and thermal hyperalgesia were evaluated by measuring the withdrawal threshold of a von Frey filament and hot/cold plate latency. Western blotting was performed to determine the expression levels of Trpv1, Nav1.9, calci-tonin gene-related peptide (CGRP), and beta-actin in damaged tissue.Results: The withdrawal threshold values and latency of the D-serine group were significant-ly lower than those of the noninjection group. The MK-801 group showed higher threshold values and latencies than the other groups. Western blotting showed increased Nav1.9 and Trpv1 levels and lower CGRP levels in the D-serine group, whereas the MK-801 group showed the opposite results.Conclusion: D-serine increases neuropathic pain after traumatic SCI by mediating the NMDA receptor. NMDA receptor antagonists alleviate neuropathic pain after traumatic SCI.

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