title: Electrophysiological characterization of spinal neuron sensitization by elevated calcium channel alpha-2-delta-1 subunit protein.
abstract: BACKGROUND
  Voltage-gated calcium channel α2 δ1 subunit is the binding site for gabapentin, an effective drug in controlling neuropathic pain states including thermal hyperalgesia. Hyperalgesia to noxious thermal stimuli in both spinal nerve-ligated (SNL) and voltage-gated calcium channel α2 δ1 overexpressing transgenic (Tg) mice correlates with higher α2 δ1 levels in dorsal root ganglia and dorsal spinal cord. In this study, we investigated whether abnormal synaptic transmission is responsible for thermal hyperalgesia induced by elevated α2 δ1 expression in these models.
  
  
  METHODS
  Behavioural sensitivities to thermal stimuli were test in L4 SNL and sham mice, as well as in α2 δ1 Tg and wild-type mice. Miniature excitatory (mEPSC) and inhibitory (mIPSC) post-synaptic currents were recorded in superficial dorsal spinal cord neurons from these models using whole-cell patch clamp slice recording techniques.
  
  
  RESULTS
  The frequency, but not amplitude, of mEPSC in superficial dorsal horn neurons was increased in SNL and α2 δ1 Tg mice, which could be attenuated by gabapentin dose dependently. Intrathecal α2 δ1 antisense oligodeoxynucleotide treatment diminished increased mEPSC frequency and gabapentin's inhibitory effects in elevated mEPSC frequency in the SNL mice. In contrast, neither the frequency nor the amplitude of mIPSC was altered in superficial dorsal horn neurons from the SNL and α2 δ1 Tg mice.
  
  
  CONCLUSIONS
  Our findings support a role of peripheral nerve injury-induced α2 δ1 in enhancing pre-synaptic excitatory input onto superficial dorsal spinal cord neurons that contributes to nociception development.
authors.affiliation: Department of Pharmacology, School of Medicine, University of California Irvine, USA.
authors.forename: C
authors.initials: C
authors.lastname: Zhou
authors.forename: Z D
authors.initials: ZD
authors.lastname: Luo
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D003080:Cold Temperature; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C512066:CACNA2D1 protein, mouse; D015220:Calcium Channels; D020319:Oligodeoxyribonucleotides, Antisense