Upregulation of α2δ−1 Calcium Channel Subunit in the Spinal Cord Contributes to Pelvic Organ Cross-Sensitization in a Rat Model of Experimentally-Induced Endometriosis

Abstract

Pelvic organ cross-sensitization, also termed as viscero-visceral referred hyperalgesia, is a major contributor to painful endometriosis. Its underlying mechanism is poorly understood. Clinical and basic studies have shown that gabapentin, a drug that binds to the α2δ−1 subunit of voltage-dependent calcium channels (Cavα2δ−1), is effective in treating chronic visceral pain. Accordingly, we hypothesized that pelvic organ cross-sensitization in painful endometriosis is mediated by an upregulation of Cavα2δ−1 in the spinal cord. We examined if the dysregulation of spinal Cavα2δ−1 subunit may play an important role in the development of ectopic growths-to-colon cross-sensitization in a rat model of experimentally-induced endometriosis. Our findings suggest that there was an increased Cavα2δ−1 expression in the dorsal horn and an ectopic growths-to-colon cross-sensitization in female rats with established endometriosis. Intrathecal administration of gabapentin (300 μg) remarkably reduced the ectopic growths-to-colon cross-sensitization in rats with established endometriosis. Furthermore, intrathecal injection of Cavα2δ−1 antisense oligodeoxynucleotides reversed the ectopic growths-to-colon cross-sensitization and also normalized the upregulation of spinal Cavα2δ−1 expression in endometriosis rats. The current study suggests that the upregulation of Cavα2δ−1 in the spinal cord may contribute to pelvic organ cross-sensitization in painful endometriosis. Our study may provide a biological basis for selectively targeting this pathway to relieve viscero-visceral referred hyperalgesia in patients with painful endometriosis.

DOI: 10.1007/s11064-015-1592-3

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@article{Wang2015UpregulationO, title={Upregulation of α2δ−1 Calcium Channel Subunit in the Spinal Cord Contributes to Pelvic Organ Cross-Sensitization in a Rat Model of Experimentally-Induced Endometriosis}, author={Yun Wang and Meijuan Zhang and Fang Xie and Xueyang Li and Mengmeng Bao and Ning Yang and Rong Shi and Zhenyuan Wang and Anshi Wu and Yun Guan and Y. Yue}, journal={Neurochemical Research}, year={2015}, volume={40}, pages={1267-1273} }