Spinal Dorsal Horn Calcium Channel Alpha2delta-1 Subunit Upregulation Contributes to Peripheral Nerve Injury-induced Tactile Allodynia

Overview

Journal J Neurosci

Specialty Neurology

Date 2004 Oct 1

PMID 15456823

Citations 100

Authors

Chun-Ying Li

Yan-Hua Song

Emiliano S Higuera

Z David Luo

Affiliations

Soon will be listed here.

Abstract

Peripheral nerve injury induces upregulation of the calcium channel alpha2delta-1 structural subunit in dorsal root ganglia (DRG) and dorsal spinal cord of spinal nerve-ligated rats with neuropathic pain, suggesting a role of the calcium channel alpha2delta-1 subunit in central sensitization. To investigate whether spinal dorsal horn alpha2delta-1 subunit upregulation derives from increased DRG alpha2delta-1 subunit and plays a causal role in neuropathic pain development, we examined spinal dorsal hornalpha2delta-1 subunit expression with or without dorsal rhizotomy in spinal nerve-ligated rats and its correlation with tactile allodynia, a neuropathic pain state defined as reduced thresholds to non-noxious tactile stimulation. We also examined the effects of intrathecal alpha2delta-1 antisense oligonucleotides on alpha2delta-1 subunit expression and neuropathic allodynia in the nerve-ligated rats. Our data indicated that spinal nerve injury resulted in time-dependentalpha2delta-1 subunit upregulation in the spinal dorsal horn that correlated temporally with neuropathic allodynia development and maintenance. Dorsal rhizotomy diminished basal level expression and blocked injury-induced expression of the spinal dorsal hornalpha2delta-1 subunit and reversed injury-induced tactile allodynia. In addition, intrathecal alpha2delta-1 antisense oligonucleotides blocked injury-induced dorsal horn alpha2delta-1 subunit upregulation and diminished tactile allodynia. These findings indicate that alpha2delta-1 subunit basal expression occurs presynaptically and postsynaptically in spinal dorsal horn. Nerve injury induces mainly presynaptic alpha2delta-1 subunit expression that derives from increased alpha2delta-1 subunit in injured DRG neurons. Thus, changes in presynaptic alpha2delta-1 subunit expression contribute to injury-induced spinal neuroplasticity and central sensitization that underlies neuropathic pain development and maintenance.

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