Abstract
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 α2δ-1 (hereafter referred to as α2δ) subunit of voltage-gated calcium channels. We hypothesized that nerve injury may result in altered α2δ 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 α2δ subunit expression in DRGs ipsilateral to the nerve injury. Marked α2δ 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 α2δ subunit expression preceded the allodynia onset and diminished in rats recovering from tactile allodynia. RNase protection experiments indicated that the DRG α2δ regulation was at the mRNA level. In contrast, calcium channel α1B and β3 subunit expression was not co-upregulated with the α2δ subunit after nerve injury. These data suggest that DRG α2δ regulation may play an unique role in neuroplasticity after peripheral nerve injury that may contribute to allodynia development.