Korean J Pain.  2009 Dec;22(3):210-215. 10.3344/kjp.2009.22.3.210.

NMDA Receptor Activation Mediates Neuropathic Pain States Induced by Calcium Channel alpha2delta1 Subunit

• Yu SB
• Lim YS
• Kim DS

• KMID: 1978695
• DOI: http://doi.org/10.3344/kjp.2009.22.3.210

Abstract

BACKGROUND: Several studies have indicated that a nerve injury enhances the expression of the voltage-gated calcium channel alpha2delta1 subunit (Cavalpha2delta1) in sensory neurons and the dorsal spinal cord. This study examined whether NMDA receptor activation is essential for Cavalpha2delta1-mediated tactile allodynia in Cavalpha2delta1 overexpressing transgenic mice and L5/6 spinal nerve ligated rats (SNL). These two models show similar Cavalpha2delta1 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 10microl 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 Cavalpha2delta1 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 Cavalpha2delta1 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.

Keyword

allodynia; calcium channel alpha2delta1 subunit; memantine; NMDA receptor

MeSH Terms

Animals
Calcium
Calcium Channels
Hyperalgesia
Hypersensitivity
Injections, Spinal
Memantine
Mice
Mice, Transgenic
N-Methylaspartate
Negotiating
Neuralgia
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate
Sensory Receptor Cells
Spinal Cord
Spinal Nerves
Up-Regulation
Calcium
Calcium Channels
Memantine
N-Methylaspartate
Receptors, N-Methyl-D-Aspartate