신경병증성 통증과정의 NMDA 수용체 활성과 칼슘통로 α2δ1 Subunit의 영향
NMDA Receptor Activation Mediates Neuropathic Pain States Induced by Calcium Channel α2δ1 Subunit
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Background: Several studies have indicated that a nerve injury enhances the expression of the voltage-gated calcium channel α2δ1 subunit (Cavα2δ1) in sensory neurons and the dorsal spinal cord. This study examined whether NMDA receptor activation is essential for Cavα2δ1-mediated tactile allodynia in Cavα2δ1 over- expressing transgenic mice and L5/6 spinal nerve ligated rats (SNL). These two models show similar Cavα2δ1 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 ㎎/㎏ (10 ㎕) was injected directly into the L5/6 spinal region followed by 10㎕ 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 ㎎/㎏ at 1.5 hours. The tactile allodynia in the Cavα2δ1 over-expressing TG mice could be reversed by an intrathecal injection of memantine 2 ㎎/㎏ 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 Cavα2δ1 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.
Abstract
Background: Several studies have indicated that a nerve injury enhances the expression of the voltage-gated calcium channel α2δ1 subunit (Cavα2δ1) in sensory neurons and the dorsal spinal cord. This study examined whether NMDA receptor activation is essential for Cavα2δ1-mediated tactile allodynia in Cavα2δ1 over- expressing transgenic mice and L5/6 spinal nerve ligated rats (SNL). These two models show similar Cavα2δ1 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 ㎎/㎏ (10 ㎕) was injected directly into the L5/6 spinal region followed by 10㎕ 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 ㎎/㎏ at 1.5 hours. The tactile allodynia in the Cavα2δ1 over-expressing TG mice could be reversed by an intrathecal injection of memantine 2 ㎎/㎏ 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 Cavα2δ1 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.
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