The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
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NMDA Receptor Activation Mediates Neuropathic Pain States Induced by Calcium Channel α2δ1 Subunit

신경병증성 통증과정의 NMDA 수용체 활성과 칼슘통로 α2δ1 Subunit의 영향

  • Yu, Soo Bong (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Lim, Young Soo (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine) ;
  • Kim, Doo Sik (Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine)
  • 유수봉 (고신대학교 의과대학 마취통증의학교실) ;
  • 임영수 (고신대학교 의과대학 마취통증의학교실) ;
  • 김두식 (고신대학교 의과대학 마취통증의학교실)
  • Received : 2009.10.15
  • Accepted : 2009.11.27
  • Published : 2009.12.01
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Abstract

Background: Several studies have indicated that a nerve injury enhances the expression of the voltage-gated calcium channel ${\alpha}2{\delta}1$ subunit (Cav ${\alpha}2{\delta}1$) in sensory neurons and the dorsal spinal cord. This study examined whether NMDA receptor activation is essential for Cav ${\alpha}2{\delta}1$-mediated tactile allodynia in Cav ${\alpha}2{\delta}1$ overexpressing transgenic mice and L5/6 spinal nerve ligated rats (SNL). These two models show similar Cav ${\alpha}2{\delta}1$ 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 $10{\mu}l$ 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 Cav ${\alpha}2{\delta}1$ 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 Cav ${\alpha}2{\delta}1$ 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.

Keywords

Acknowledgement

Supported by : 고신대학교 의과대학

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