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The Journal of Neuroscience, March 15, 2001, 21(6):1868-1875

Upregulation of Dorsal Root Ganglion ₂ Calcium Channel Subunit and Its Correlation with Allodynia in Spinal Nerve-Injured Rats

Z. David Luo¹, Sandra R. Chaplan¹, Emiliano S. Higuera¹, Linda S. Sorkin¹, Kenneth A. Stauderman², Mark E. Williams², and Tony L. Yaksh¹

¹ Department of Anesthesiology, University of California, San Diego, La Jolla, California 92093-0818, and ² SIBIA Neurosciences, Inc., La Jolla, California 92037

Peripheral nerve injury can lead to a persistent neuropathic pain state in which innocuous tactile stimulation elicits pain behavior (tactile allodynia). Spinal administration of the anticonvulsant gabapentin suppresses allodynia by an unknown mechanism. In vitro studies indicate that gabapentin binds to the ₂-1 (hereafter referred to as ₂) subunit of voltage-gated calcium channels. We hypothesized that nerve injury may result in altered ₂ subunit expression in spinal cord and dorsal root ganglia (DRGs) and that this change may play a role in neuropathic pain processing. Using a rat neuropathic pain model in which gabapentin-sensitive tactile allodynia develops after tight ligation of the left fifth and sixth lumbar spinal nerves, we found a >17-fold, time-dependent increase in ₂ subunit expression in DRGs ipsilateral to the nerve injury. Marked ₂ subunit upregulation was also evident in rats with unilateral sciatic nerve crush, but not dorsal rhizotomy, indicating a peripheral origin of the expression regulation. The increased ₂ subunit expression preceded the allodynia onset and diminished in rats recovering from tactile allodynia. RNase protection experiments indicated that the DRG ₂ regulation was at the mRNA level. In contrast, calcium channel _1B and ₃ subunit expression was not co-upregulated with the ₂ subunit after nerve injury. These data suggest that DRG ₂ regulation may play an unique role in neuroplasticity after peripheral nerve injury that may contribute to allodynia development.

Key words: ₂ calcium channel subunit; peripheral nerve injury; rhizotomy; allodynia; dorsal root ganglia; spinal cord; sensory neurons

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Copyright © 2001 Society for Neuroscience  0270-6474/01/2161868-08$05.00/0

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