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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

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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.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (30801073, 81171055, 81428008), Bei**g Municipal Natural Science Foundation (7152056), New Century Excellent Talents Program from the Ministry of Education, China (NCET-10-0014), the Excellent Program for Scientific Activity of Returned Oversea Scholar, Bei**g, China (2013), and the Program for High Levels of Health Personnel in Bei**g City, China (2013).

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Authors and Affiliations

  1. Department of Anesthesiology, Bei**g Chaoyang Hospital, Capital Medical University, No. 8, Gongtinan Road, Chaoyang District, Bei**g, 100020, China

    Yun Wang, Meijuan Zhang, Fang **e, Xueyang Li, Mengmeng Bao, Ning Yang, Rong Shi, Zhenyuan Wang, Anshi Wu & Yun Yue

  2. Department of Anesthesiology, Tongren Hospital, Capital Medical University, Bei**g, 100025, China

    Meijuan Zhang

  3. Department of Anesthesiology, Bei**g Hospital, Peking University Health Science Center, Bei**g, 100730, China

    Ning Yang

  4. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, 21205, USA

    Yun Guan

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  1. Yun Wang
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  2. Meijuan Zhang
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  3. Fang **e
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Correspondence to Yun Wang.

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Wang, Y., Zhang, M., **e, F. et al. 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. Neurochem Res 40, 1267–1273 (2015). https://doi.org/10.1007/s11064-015-1592-3

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  • DOI: https://doi.org/10.1007/s11064-015-1592-3

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