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Research ArticleNEUROPHARMACOLOGY

Injury Type-Specific Calcium Channel α2δ-1 Subunit Up-Regulation in Rat Neuropathic Pain Models Correlates with Antiallodynic Effects of Gabapentin

Z. D. Luo, N. A. Calcutt, E. S. Higuera, C. R. Valder, Y.-H. Song, C. I. Svensson and R. R. Myers
Journal of Pharmacology and Experimental Therapeutics December 2002, 303 (3) 1199-1205; DOI: https://doi.org/10.1124/jpet.102.041574
Z. D. Luo
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N. A. Calcutt
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E. S. Higuera
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C. R. Valder
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Y.-H. Song
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C. I. Svensson
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R. R. Myers
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Abstract

The calcium channel α2δ-1 subunit is a structural subunit important for functional calcium channel assembly. In vitro studies have shown that this subunit is the binding site for gabapentin, an anticonvulsant that exerts antihyperalgesic effects by unknown mechanisms. Increased expression of this subunit in the spinal cord and dorsal root ganglia (DRG) has been suggested to play a role in enhanced nociceptive responses of spinal nerve-injured rats to innocuous mechanical stimulation (allodynia). To investigate whether a common mechanism underlies allodynic states derived from different etiologies, and if so, whether similar α2δ-1 subunit up-regulation correlates with these allodynic states, we compared DRG and spinal cord α2δ-1 subunit levels and gabapentin sensitivity in allodynic rats with mechanical nerve injuries (sciatic nerve chronic constriction injury, spinal nerve transection, or ligation), a metabolic disorder (diabetes), or chemical neuropathy (vincristine neurotoxicity). Our data indicated that even though allodynia occurred in all types of nerve injury investigated, DRG and/or spinal cord α2δ-1 subunit up-regulation and gabapentin sensitivity only coexisted in the mechanical and diabetic neuropathies. Thus, induction of the α2δ-1 subunit in the DRG and spinal cord is likely regulated by factors that are specific for individual neuropathies and may contribute to gabapentin-sensitive allodynia. However, the calcium channel α2δ-1 subunit is not the sole molecular change that uniformly characterizes the neuropathic pain states.

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Journal of Pharmacology and Experimental Therapeutics: 303 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 303, Issue 3
1 Dec 2002
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Research ArticleNEUROPHARMACOLOGY

Injury Type-Specific Calcium Channel α2δ-1 Subunit Up-Regulation in Rat Neuropathic Pain Models Correlates with Antiallodynic Effects of Gabapentin

Z. D. Luo, N. A. Calcutt, E. S. Higuera, C. R. Valder, Y.-H. Song, C. I. Svensson and R. R. Myers
Journal of Pharmacology and Experimental Therapeutics December 1, 2002, 303 (3) 1199-1205; DOI: https://doi.org/10.1124/jpet.102.041574

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Research ArticleNEUROPHARMACOLOGY

Injury Type-Specific Calcium Channel α2δ-1 Subunit Up-Regulation in Rat Neuropathic Pain Models Correlates with Antiallodynic Effects of Gabapentin

Z. D. Luo, N. A. Calcutt, E. S. Higuera, C. R. Valder, Y.-H. Song, C. I. Svensson and R. R. Myers
Journal of Pharmacology and Experimental Therapeutics December 1, 2002, 303 (3) 1199-1205; DOI: https://doi.org/10.1124/jpet.102.041574
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