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Eur J Pain. 2015 Oct;19(9):1267-76. doi: 10.1002/ejp.656. Epub 2015 Feb 17.

Nerve injury-induced calcium channel alpha-2-delta-1 protein dysregulation leads to increased pre-synaptic excitatory input into deep dorsal horn neurons and neuropathic allodynia.

Author information

1
Department of Pharmacology, School of Medicine, University of California Irvine, USA.
2
Department of Anesthesiology and Perioperative Care, School of Medicine, University of California Irvine, USA.

Abstract

BACKGROUND:

Up-regulation of voltage-gated calcium channel α2 δ1 subunit post spinal nerve ligation (SNL) injury or in α2 δ1 -overexpressing transgenic (Tg) mice correlates with tactile allodynia, a pain state mediated mainly by Aβ sensory fibres forming synaptic connections with deep dorsal horn (DDH) neurons. It is not clear, however, whether dysregulated α2 δ1 alters DDH synaptic neurotransmission that underlies tactile allodynia development post nerve injury.

METHODS:

Tactile allodynia was tested in the SNL and α2 δ1 Tg models. Miniature excitatory/inhibitory post-synaptic currents were recorded in DDH neurons from these animal models using whole-cell patch clamp slice recording techniques.

RESULTS:

There was a significant increase in the frequency, but not amplitude, of miniature excitatory post-synaptic currents (mEPSC) in DDH neurons that correlated with tactile allodynia in SNL and α2 δ1 Tg mice. Gabapentin, an α2 δ1 ligand that is known to block tactile allodynia in these models, also normalized mEPSC frequency dose-dependently in DDH neurons from SNL and α2 δ1 Tg mice. In contrast, neither frequency nor amplitude of miniature inhibitory post-synaptic currents was altered in DDH neurons from SNL and α2 δ1 Tg mice.

CONCLUSION:

Our data suggest that α2 δ1 dysregulation is highly likely contributing to tactile allodynia through a pre-synaptic mechanism involving facilitation of excitatory synaptic neurotransmission in DDH of spinal cord.

PMID:
25691360
PMCID:
PMC4539283
DOI:
10.1002/ejp.656
[Indexed for MEDLINE]
Free PMC Article

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