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A Nociceptive Role for Integrin Signaling in Pain After Mechanical Injury to the Spinal Facet Capsular Ligament

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Abstract

Integrins modulate chemically-induced nociception in a variety of inflammatory and neuropathic pain models. Yet, the role of integrins in mechanically-induced pain remains undefined, despite its well-known involvement in cell adhesion and mechanotransduction. Excessive spinal facet capsular ligament stretch is a common injury that induces morphological and functional changes in its innervating afferent neurons and can lead to pain. However, the local mechanisms underlying the translation from tissue deformation to pain signaling are unclear, impeding effective treatment. Therefore, the involvement of the integrin subunit β1 in pain signaling from facet injury was investigated in complementary in vivo and in vitro studies. An anatomical study in the rat identified expression of the integrin subunit β1 in dorsal root ganglion (DRG) neurons innervating the facet, with greater expression in peptidergic than non-peptidergic DRG neurons. Painful facet capsule stretch in the rat upregulated the integrin subunit β1 in small- and medium-diameter DRG neurons at day 7. Inhibiting the α2β1 integrin in a DRG-collagen culture prior to its stretch injury prevented strain-induced increases in axonal substance P (SP) in a dose-dependent manner. Together, these findings suggest that integrin subunit β1-dependent pathways may contribute to SP-mediated pain from mechanical injury of the facet capsular ligament.

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Acknowledgments

This work was supported by a Grant from the NIH (U01EB016638), an AMTI Force and Motion Scholarship, and an NSF training Grant (#1548571). We thank Dr. Jeffrey Kras for generating the DRG tissue from the naïve, injured and sham groups for the in vivo studies, Jasmine Lee for assisting with tissue preparation and Dr. D. Kacy Cullen for advice about inhibition. We are grateful to the Neuron Culture Service Center of the Mahoney Institute of Neurological Science at the University of Pennsylvania for providing the rat embryos.

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The authors declare no conflict of interest.

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  1. Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 S. 33rd St, Philadelphia, PA, 19104-6321, USA

    Sijia Zhang, Ethan Zhao & Beth A. Winkelstein

  2. Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Beth A. Winkelstein

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  1. Sijia Zhang
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Associate Editor Mona Kamal Marei oversaw the review of this article.

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Zhang, S., Zhao, E. & Winkelstein, B.A. A Nociceptive Role for Integrin Signaling in Pain After Mechanical Injury to the Spinal Facet Capsular Ligament. Ann Biomed Eng 45, 2813–2825 (2017). https://doi.org/10.1007/s10439-017-1917-2

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