51. Neuroinflammation of the spinal cord and nerve roots in chronic radicular pain patients.
- Author
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Albrecht DS, Ahmed SU, Kettner NW, Borra RJH, Cohen-Adad J, Deng H, Houle TT, Opalacz A, Roth SA, Melo MFV, Chen L, Mao J, Hooker JM, Loggia ML, and Zhang Y
- Subjects
- Adult, Aged, Chronic Pain metabolism, Chronic Pain physiopathology, Cross-Sectional Studies, Female, Humans, Inflammation metabolism, Inflammation physiopathology, Magnetic Resonance Imaging, Male, Middle Aged, Positron-Emission Tomography, Radiculopathy metabolism, Radiculopathy physiopathology, Receptors, GABA metabolism, Spinal Cord metabolism, Spinal Cord physiopathology, Spinal Nerve Roots metabolism, Spinal Nerve Roots physiopathology, Young Adult, Chronic Pain diagnostic imaging, Inflammation diagnostic imaging, Radiculopathy diagnostic imaging, Spinal Cord diagnostic imaging, Spinal Nerve Roots diagnostic imaging
- Abstract
Numerous preclinical studies support the role of spinal neuroimmune activation in the pathogenesis of chronic pain, and targeting glia (eg, microglia/astrocyte)- or macrophage-mediated neuroinflammatory responses effectively prevents or reverses the establishment of persistent nocifensive behaviors in laboratory animals. However, thus far, the translation of those findings into novel treatments for clinical use has been hindered by the scarcity of data supporting the role of neuroinflammation in human pain. Here, we show that patients suffering from a common chronic pain disorder (lumbar radiculopathy), compared with healthy volunteers, exhibit elevated levels of the neuroinflammation marker 18 kDa translocator protein, in both the neuroforamina (containing dorsal root ganglion and nerve roots) and spinal cord. These elevations demonstrated a pattern of spatial specificity correlating with the patients' clinical presentation, as they were observed in the neuroforamen ipsilateral to the symptomatic leg (compared with both contralateral neuroforamen in the same patients as well as to healthy controls) and in the most caudal spinal cord segments, which are known to process sensory information from the lumbosacral nerve roots affected in these patients (compared with more superior segments). Furthermore, the neuroforaminal translocator protein signal was associated with responses to fluoroscopy-guided epidural steroid injections, supporting its role as an imaging marker of neuroinflammation, and highlighting the clinical significance of these observations. These results implicate immunoactivation at multiple levels of the nervous system as a potentially important and clinically relevant mechanism in human radicular pain, and suggest that therapies targeting immune cell activation may be beneficial for chronic pain patients.
- Published
- 2018
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