Original Article

Korean J Pain 2009; 22(3): 210-215

Published online December 30, 2009 https://doi.org/10.3344/kjp.2009.22.3.210

Copyright © The Korean Pain Society.

NMDA Receptor Activation Mediates Neuropathic Pain States Induced by Calcium Channel Ձ2Մ1 Subunit

Soo Bong Yu, M.D., Young Soo Lim, M.D., and Doo Sik Kim, M.D.

Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine, Busan, Korea

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background: Several studies have indicated that a nerve injury enhances the expression of the voltage-gated calcium channel Ձ2Մ1 subunit (CavՁ2Մ1) in sensory neurons and the dorsal spinal cord. This study examined whether NMDA receptor activation is essential for CavՁ2Մ1-mediated tactile allodynia in CavՁ2Մ1 over- expressing transgenic mice and L5/6 spinal nerve ligated rats (SNL). These two models show similar CavՁ2Մ1 upregulation and behavioral hypersensitivity, without and with the presence of other injury factors, respectively.
Methods: The transgenic (TG) mice were generated as described elsewhere (Feng et al., 2000). The left L5/6 spinal nerves in the Harlan Sprague Dawley rats were ligated tightly (SNL) to induce neuropathic pain, as described by Kim et al. (1992). Memantine 2 mg/kg (10 ul) was injected directly into the L5/6 spinal region followed by 10Ռl saline. Tactile allodynia was tested for any mechanical hypersensitivity.
Results: The tactile allodynia in the SNL rats could be reversed by an intrathecal injection of memantine 2 mg/kg at 1.5 hours. The tactile allodynia in the CavՁ2Մ1 over-expressing TG mice could be reversed by an intrathecal injection of memantine 2 mg/kg at 1.5, 2.0 and 2.5 hours.
Conclusions: The behavioral hypersensitivity was similar in the TG mice and nerve injury pain model, supporting the hypothesis that elevated CavՁ2Մ1 mediates similar pathways that underlie the pain states in both models. The selective activation of spinal NMDA receptors plays a key role in mediating the pain states in both the nerve-injury rats and TG mice. (Korean J Pain 2009; 22: 210-215)

Keywords: allodynia, calcium channel Ձ,2Մ,1 subunit, memantine, NMDA receptor