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

Previous studies have shown that peripheral nerve injury in rats induces increased of the voltage gated calcium channel (VGCC) alpha-2-delta-1 subunit (Ca-v alpha(2)delta(1))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 Ca-v alpha(2)delta(1) induction that contributes to neuropathic pain initiation, we examined allodynia onset and Ca-v alpha(2)delta(1) levels in DRG and spinal dorsal horn of spinal nerve ligated rats after blocking injury induced neural activity with a local brief application of lidoaine on spinal nerves before the ligation. The lidocaine pretreatment blocked ligaton-induced discharges in a dose-dependent manner. Similar pretreatment with the effective concentration of lidocaine diminished injury-induced increases of the Ca-v alpha(2)delta(1) in DRG and abolished that in spinal dorsal horn specifically, and resulted in a delayed onset of tactile allodynia post-injury. Both dorsal horn Ca-v alpha(2)delta(1) 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 Ca-v alpha(2)delta(1) antisense treatments blocked concurrently injury-induced allodynia onset and Ca-v alpha(2)delta(1) upregulation in dorsal spinal cord. These findings indicate that injury induced discharges regulate Ca-v alpha(2)delta(1) expression in the spinal dorsal horn that is critical for neuropathic allodynia initiation. Thus, preemptive blockade of injury-induced neural activity or Ca-v alpha(2)delta(1) upregultion may be a beneficial option in neuropathic pain management. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.