Upregulation of Dorsal Root Ganglion a2d Calcium Channel Subunit and Its Correlation with Allodynia in Spinal Nerve-Injured Rats

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 a2d-1 (hereafter referred to as a2d) subunit of voltage-gated calcium channels. We hypothesized that nerve injury may result in altered a2d 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 a2d subunit expression in DRGs ipsilateral to the nerve injury. Marked a2d 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 a2d subunit expression preceded the allodynia onset and diminished in rats recovering from tactile allodynia. RNase protection experiments indicated that the DRG a2d regulation was at the mRNA level. In contrast, calcium channel a1B and b3 subunit expression was not co-upregulated with the a2d subunit after nerve injury. These data suggest that DRG a2d regulation may play an unique role in neuroplasticity after peripheral nerve injury that may contribute to allodynia development.