期刊
JOURNAL OF NEUROSCIENCE
卷 24, 期 39, 页码 8494-8499出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2982-04.2004
关键词
central sensitization; spinal cord; allodynia; neuropathic pain; nerve injury; calcium channels
资金
- NIDCR NIH HHS [DE13270, DE14545, R21 DE014545] Funding Source: Medline
- NINDS NIH HHS [NS40135, R01 NS040135] Funding Source: Medline
Peripheral nerve injury induces upregulation of the calcium channel alpha(2)delta-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 alpha(2)delta-1 subunit in central sensitization. To investigate whether spinal dorsal horn alpha(2)delta-1 subunit upregulation derives from increased DRG alpha(2)delta-1 subunit and plays a causal role in neuropathic pain development, we examined spinal dorsal horn alpha(2)delta-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 alpha(2)delta-1 antisense oligonucleotides on alpha(2)delta-1 subunit expression and neuropathic allodynia in the nerve-ligated rats. Our data indicated that spinal nerve injury resulted in time-dependent alpha(2)delta-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 horn alpha(2)delta-1 subunit and reversed injury-induced tactile allodynia. In addition, intrathecal alpha(2)delta-1 antisense oligonucleotides blocked injury-induced dorsal horn alpha(2)delta-1 subunit upregulation and diminished tactile allodynia. These findings indicate that alpha(2)delta-1 subunit basal expression occurs presynaptically and postsynaptically in spinal dorsal horn. Nerve injury induces mainly presynaptic alpha(2)delta-1 subunit expression that derives from increased alpha(2)delta-1 subunit in injured DRG neurons. Thus, changes in presynaptic alpha(2)delta-1 subunit expression contribute to injury-induced spinal neuroplasticity and central sensitization that underlies neuropathic pain development and maintenance.
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