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

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Abstract
. 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....