Neuroinflammation of the spinal cord and nerve roots in chronic radicular pain patients
- 1 May 2018
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Pain
- Vol. 159 (5), 968-977
- https://doi.org/10.1097/j.pain.0000000000001171
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.Keywords
This publication has 49 references indexed in Scilit:
- The Upregulation of Translocator Protein (18 kDa) Promotes Recovery from Neuropathic Pain in RatsJournal of Neuroscience, 2013
- RELIEVING PAIN IN AMERICA: A BLUEPRINT FOR TRANSFORMING PREVENTION, CARE, EDUCATION, AND RESEARCHJournal of Pain & Palliative Care Pharmacotherapy, 2012
- An 18-kDa Translocator Protein (TSPO) Polymorphism Explains Differences in Binding Affinity of the PET Radioligand PBR28Journal of Cerebral Blood Flow & Metabolism, 2011
- Minocycline injection in the ventral posterolateral thalamus reverses microglial reactivity and thermal hyperalgesia secondary to sciatic neuropathyNeuroscience Letters, 2011
- Astroglia in Medullary Dorsal Horn (Trigeminal Spinal Subnucleus Caudalis) Are Involved in Trigeminal Neuropathic Pain MechanismsJournal of Neuroscience, 2009
- Brain and whole-body imaging in nonhuman primates of [11C]PBR28, a promising PET radioligand for peripheral benzodiazepine receptorsNeuroImage, 2008
- Glial–Cytokine–Neuronal Interactions Underlying the Mechanisms of Persistent PainJournal of Neuroscience, 2007
- Immunohistochemical Assessment of the Peripheral Benzodiazepine Receptor in Human TissuesJournal of Histochemistry & Cytochemistry, 2004
- Inhibition of Microglial Activation Attenuates the Development but Not Existing Hypersensitivity in a Rat Model of NeuropathyJournal of Pharmacology and Experimental Therapeutics, 2003
- The possible role of glia in nociceptive processing and hyperalgesia in the spinal cord of the ratNeuropharmacology, 1994