Calcium channel alpha-2-delta-1 protein upregulation in dorsal spinal cord mediates spinal cord injury-induced neuropathic pain states

Pain. 2011 Mar;152(3):649-655. doi: 10.1016/j.pain.2010.12.014. Epub 2011 Jan 15.


Spinal cord injury (SCI) commonly results in the development of neuropathic pain, which can dramatically impair the quality of life for SCI patients. SCI-induced neuropathic pain can be manifested as both tactile allodynia (a painful sensation to a non-noxious stimulus) and hyperalgesia (an enhanced sensation to a painful stimulus). The mechanisms underlying these pain states are poorly understood. Clinical studies have shown that gabapentin, a drug that binds to the voltage-gated calcium channel alpha-2-delta-1 subunit (Ca(v)α2δ-1) proteins is effective in the management of SCI-induced neuropathic pain. Accordingly, we hypothesized that tactile allodynia post SCI is mediated by an upregulation of Ca(v)α2δ-1 in dorsal spinal cord. To test this hypothesis, we examined whether SCI-induced dysregulation of spinal Ca(v)α2δ-1 plays a contributory role in below-level allodynia development in a rat spinal T9 contusion injury model. We found that Ca(v)α2δ-1 expression levels were significantly increased in L4-6 dorsal, but not ventral, spinal cord of SCI rats that correlated with tactile allodynia development in the hind paw plantar surface. Furthermore, both intrathecal gabapentin treatment and blocking SCI-induced Ca(v)α2δ-1 protein upregulation by intrathecal Ca(v)α2δ-1 antisense oligodeoxynucleotides could reverse tactile allodynia in SCI rats. These findings support that SCI-induced Ca(v)α2δ-1 upregulation in spinal dorsal horn is a key component in mediating below-level neuropathic pain states, and selectively targeting this pathway may provide effective pain relief for SCI patients. Spinal cord contusion injury caused increased calcium channel Ca(v)α2δ-1 subunit expression in dorsal spinal cord that contributes to neuropathic pain states.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amines / therapeutic use
  • Analgesics / therapeutic use
  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type
  • Cyclohexanecarboxylic Acids / therapeutic use
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Gabapentin
  • Hyperalgesia / etiology
  • Hyperalgesia / metabolism
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neuralgia / drug therapy
  • Neuralgia / etiology*
  • Neuralgia / pathology*
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • Pain Measurement
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism*
  • Spinal Cord Injuries / complications*
  • Statistics as Topic
  • Time Factors
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*
  • gamma-Aminobutyric Acid / therapeutic use


  • Amines
  • Analgesics
  • Cacna2d1 protein, rat
  • Calcium Channels
  • Calcium Channels, L-Type
  • Cyclohexanecarboxylic Acids
  • Oligodeoxyribonucleotides, Antisense
  • gamma-Aminobutyric Acid
  • Gabapentin