Injury discharges regulate calcium channel alpha-2-delta-1 subunit upregulation in the dorsal horn that contributes to initiation of neuropathic pain.
Pain
; 139(2): 358-366, 2008 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-18571852
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 (Ca v alpha2 delta1) 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 alpha2 delta1 induction that contributes to neuropathic pain initiation, we examined allodynia onset and Ca v alpha2 delta1 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 Ca v alpha2 delta1 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 alpha2 delta1 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 alpha2 delta1 antisense treatments blocked concurrently injury-induced allodynia onset and Ca v alpha2 delta1 upregulation in dorsal spinal cord. These findings indicate that injury induced discharges regulate Ca v alpha2 delta1 expression in the spinal dorsal horn that is critical for neuropathic allodynia initiation. Thus, preemptive blockade of injury-induced neural activity or Ca v alpha2 delta1 upregulation may be a beneficial option in neuropathic pain management.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Nervos Espinhais
/
Canais de Cálcio
/
Células do Corno Posterior
/
Hiperalgesia
/
Neuralgia
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article