Upregulation of dorsal root ganglion (alpha)2(delta) 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 alpha(2)delta-1 (hereafter referred to as alpha(2)delta) subunit of voltage-gated calcium channels. We hypothesized that nerve injury may result in altered alpha(2)delta 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 alpha(2)delta subunit expression in DRGs ipsilateral to the nerve injury. Marked alpha(2)delta 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 alpha(2)delta subunit expression preceded the allodynia onset and diminished in rats recovering from tactile allodynia. RNase protection experiments indicated that the DRG alpha(2)delta regulation was at the mRNA level. In contrast, calcium channel alpha(1B) and beta(3) subunit expression was not co-upregulated with the alpha(2)delta subunit after nerve injury. These data suggest that DRG alpha(2)delta regulation may play an unique role in neuroplasticity after peripheral nerve injury that may contribute to allodynia development.
Department of Anesthesiology, University of California, San Diego, La Jolla, California 92093-0818, USA. zluo@ucsd.edu
Z D
ZD
Luo
S R
SR
Chaplan
E S
ES
Higuera
L S
LS
Sorkin
K A
KA
Stauderman
M E
ME
Williams
T L
TL
Yaksh
D000818:Animals; D001369:Axons / Q000378:metabolism; D001522:Behavior, Animal; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000503:physiopathology; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D008026:Ligation; D008297:Male; D009409:Nerve Crush; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D010147:Pain Measurement; D021122:Protein Subunits; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019051:Rhizotomy; D012584:Sciatic Nerve / Q000502:physiology / Q000601:surgery; D013127:Spinal Nerves / Q000293:injuries* / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation
D015220:Calcium Channels; D021122:Protein Subunits; D012333:RNA, Messenger