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

作者：Zhang Sijia; Zhao Ethan; Winkelstein Beth A^*

来源：Annals of Biomedical Engineering, 2017, 45(12): 2813-2825.

DOI：10.1007/s10439-017-1917-2

• Facet joint
• Tissue strain
• Nociceptors
• Integrin subunit beta 1
• Substance P

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 beta 1 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 beta 1 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 beta 1 in small- and medium-diameter DRG neurons at day 7. Inhibiting the alpha 2 beta 1 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 beta 1-dependent pathways may contribute to SP-mediated pain from mechanical injury of the facet capsular ligament.

• 出版日期2017-12