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Calcium channel alpha2delta1 subunit mediates spinal hyperexcitability in pain modulation
Chun-Ying Li1, Xiu-Lin Zhang, Elizabeth A Matthews
1Department of Anesthesiology, School of Medicine, University of California Irvine, Irvine, CA 92697, USA.
Pain
|June 13, 2006
Summary
Overexpressing the voltage-gated calcium channel alpha2delta1 subunit (Ca(v)alpha2delta1) in neurons causes pain-related behaviors. This suggests elevated Ca(v)alpha2delta1 contributes to specific chronic pain states.
Area of Science:
- Neuroscience
- Pain Research
- Molecular Biology
Background:
- Chronic pain mechanisms, particularly neuropathic pain, remain unclear.
- Upregulation of the voltage-gated calcium channel (VGCC) alpha2delta1 subunit (Ca(v)alpha2delta1) in sensory neurons and the dorsal spinal cord is implicated in neuropathic pain following peripheral nerve injury.
Purpose of the Study:
- To investigate the role of Ca(v)alpha2delta1 in pain mechanisms without confounding injury factors.
- To create and analyze transgenic mice with constitutive neuronal Ca(v)alpha2delta1 overexpression.
Main Methods:
- Generated transgenic mice overexpressing Ca(v)alpha2delta1 in neuronal tissues.
- Assessed VGCC currents, neuronal responses to stimuli, and pain behaviors in transgenic and wild-type mice.
- Examined the pharmacological profile of pain behaviors and gabapentin's effect on VGCC currents.
Main Results:
- Ca(v)alpha2delta1 overexpression enhanced VGCC currents and altered their properties in sensory neurons.
- Transgenic mice exhibited exaggerated and prolonged dorsal horn neuronal responses to peripheral mechanical and thermal stimuli, along with pain behaviors.
- These mice showed normal responses to windup stimulation and tissue-injury/inflammatory stimuli, indicating a selective contribution of Ca(v)alpha2delta1 to specific pain modalities.
Conclusions:
- Elevated neuronal Ca(v)alpha2delta1 contributes to specific pain states by enhancing VGCC activity and dorsal horn neuron hyperexcitability.
- Gabapentin's antihyperalgesic effects may be partly due to its modulation of enhanced VGCC activity in sensory neurons.
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