| As many as 30% of Americans suffer from chronic pain. Both chemical irritation and mechanical compression have been implicated in nerve root-mediated pain. However, the relative effects of these neural insults on pain symptoms are unclear. In vivo pain models characterize tissue injury, pain symptoms, and the physiologic nociceptive mechanisms relating the two. However, differences in spinal inflammation have not been defined for painful transient cervical nerve root compression injuries. The central hypothesis of this work was that persistent cervical nerve root-mediated pain produced by mechanical injury alone is mediated through different inflammatory pathways than the pain resulting from a combined mechanical and chemical injury. Behavioral hypersensitivity was quantified after nerve root compression with and without a chemical insult to define the relative roles of each of a mechanical compression and chemical irritation in inducing persistent pain. Although spinal glial reactivity has been detected in pain models, not all of the hallmarks of glial reactivity were described and the relationships between behavioral hypersensitivity and spinal glial reactivity have not been quantified for transient mechanical loading of the cervical nerve root. Accordingly, spinal glial reactivity was temporally assessed after injury using markers of activation and cellular proliferation. Also, inflammatory cytokines in the DRG and spinal cord were quantified temporally after both painful nerve root compression injury types and the spinal cellular source of interleukin-1alpha was identified. Pharmacologic agents were used to selectively block cytokine signaling in order to identify relationships between inflammatory cytokines, behavioral hypersensitivity and spinal glial reactivity in painful nerve root injury. Finally, it remains unknown how the duration of applied compression affects resulting pain symptoms and spinal inflammation. As such, coordinated in situ and in vivo studies were completed to establish relationships between the duration of applied nerve root compression, the mechanical response of the root, and inflammatory outcomes in order to define mechanical responses induced by compression that transduce nociceptive signals and mediate pain. Collectively, studies establish relationships between nerve root compression and chemical irritation, pain symptoms, and spinal inflammation, and lay a foundation for understanding the mechanisms of nerve root injury that lead to persistent pain. |
