An in vivo model of transient cervical nerve root compression: Thresholds for mechanical allodynia and neuronal responses

During axial loading or non-physiologic motions of the neck, the cervical nerve roots can become transiently compressed by the surrounding bony structures of the intervertebral foramen. Nerve root compression of short duration often produces sustained symptoms well beyond removal of the injurious stimulus. Coupled with the fact that the majority of Americans experience significant neck pain at some point in their lives, the duration of painful symptoms leads to very high economic and societal costs. Lumbar radiculopathy models have established that chronic constriction of the dorsal root produces heightened behavioral sensitivity as well as edema, altered electrophysiology, and changes in nociceptive neuropeptide expression in the dorsal root ganglion (DRG) and spinal cord. However, few studies have investigated neuropeptide changes in the DRG and spinal cord that produce persistent mechanical allodynia following transient nerve root compression. Furthermore, in clinical scenarios, the magnitude of transient compression required to produce persistent pain remains undefined since the painful stimulus does not remain in contact with the root, as occurs for chronic or stenotic impingement. The investigations in this thesis define load thresholds for the onset and maintenance of behavioral hypersensitivity at 263mN and 38.2mN, respectively, in a rat model of cervical dorsal root compression. Further, axonal degeneration, macrophage infiltration, and neuropeptide changes in the DRG and spinal cord are examined in the context of those load thresholds to determine their relationship to persistent pain. While dorsal root axonal degeneration and decreased substance P in the DRG and spinal cord occur for loads similar to those which produce mechanical allodynia, macrophages infiltrate the compressed dorsal root for loads that do not produce persistent pain. To prevent behavioral and neuropeptide changes in the DRG, glial cell line-derived neurotrophic factor (GDNF) is delivered continuously via a degradable hydrogel to the compressed dorsal root. In this radiculopathy model, GDNF reduces behavioral hypersensitivity and prevents GDNF receptor and neuropeptide changes in nociceptive neurons following transient dorsal root compression. Together, these studies identify load thresholds for producing persistent pain symptoms in the cervical spine and suggest GDNF as a potential target for treating sustained sensitivity following transient dorsal root compression