Calcium channel {alpha}2{delta}1 proteins mediate trigeminal neuropathic pain states associated with aberrant excitatory synaptogenesis [Gene Regulation]

January 23rd, 2014 by Li, K.-W., Yu, Y. P., Zhou, C., Kim, D.-S., Lin, B., Sharp, K., Steward, O., Luo, Z. D.

To investigate a potential mechanism underlying trigeminal nerve injury-induced orofacial hypersensitivity, we used a rat model of chronic constriction injury to the infraorbital nerve (CCI-ION) to study if CCI-ION injury caused calcium channel alpha-2-delta-1 (Cavα2δ1) protein dysregulaiton in trigeminal ganglia (TG) and associated dorsal spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2). Furthermore, we studied whether this neuroplasticity contributed to spinal neuron sensitization and neuropathic pain states. CCI-ION injury caused orofacial hypersensitivity that correlated with Cavα2δ1 upregulation in TG sensory neurons and Vc/C2. Blocking Cavα2δ1 with gabapentin, a ligand for the Cavα2δ1 proteins, or Cavα2δ1 antisense oligodeoxynucleotides led to a reversal of orofacial hypersensitivity, supporting an important role of Cavα2δ1 in orofacial pain processing. Importantly, increased Cavα2δ1 in Vc/C2 superficial dorsal horn was associated with increased excitatory synaptogenesis, and increased frequency but not amplitude of miniature excitatory post-synaptic currents in dorsal horn neurons, which could be blocked by gabapentin. Thus, CCI-ION injury-induced Cavα2δ1 upregulation may contribute to orofacial neuropathic pain states through abnormal excitatory synapse formation and enhanced pre-synaptic excitatory neurotransmitter release in Vc/C2.
  • Posted in Journal of Biological Chemistry, Publications
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