Injury discharges regulate calcium channel alpha-2-delta-1 subunit upregulation in the dorsal horn that contributes to initiation of neuropathic pain

Amin Boroujerdi, Hee Kee Kim, Yeoung Su Lyu, Doo Sik Kim, Katherine W. Figueroa, Jin Mo Chung, Z. David Luo

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Previous studies have shown that peripheral nerve injury in rats induces increased expression of the voltage gated calcium channel (VGCC) alpha-2-delta-1 subunit (Cavα2δ1) in spinal dorsal horn and sensory neurons in dorsal root ganglia (DRG) that correlates to established neuropathic pain states. To determine if injury discharges trigger Cavα2δ1 induction that contributes to neuropathic pain initiation, we examined allodynia onset and Cavα2δ1 levels in DRG and spinal dorsal horn of spinal nerve ligated rats after blocking injury induced neural activity with a local brief application of lidocaine on spinal nerves before the ligation. The lidocaine pretreatment blocked ligation-induced discharges in a dose-dependent manner. Similar pretreatment with the effective concentration of lidocaine diminished injury-induced increases of the Cavα2δ1 in DRG and abolished that in spinal dorsal horn specifically, and resulted in a delayed onset of tactile allodynia post-injury. Both dorsal horn Cavα2δ1 upregulation and tactile allodynia in the lidocaine pretreated rats returned to levels similar to that in saline pretreated controls 2 weeks post the ligation injury. In addition, preemptive intrathecal Cavα2δ1 antisense treatments blocked concurrently injury-induced allodynia onset and Cavα2δ1 upregulation in dorsal spinal cord. These findings indicate that injury induced discharges regulate Cavα2δ1 expression in the spinal dorsal horn that is critical for neuropathic allodynia initiation. Thus, preemptive blockade of injury-induced neural activity or Cavα2δ1 upregulation may be a beneficial option in neuropathic pain management.

Original languageEnglish (US)
Pages (from-to)358-366
Number of pages9
JournalPain
Volume139
Issue number2
DOIs
StatePublished - Oct 15 2008

Keywords

  • Allodynia
  • Initiation
  • Nerve injury
  • Neuropathic pain
  • Spinal neuroplasticity

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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