Cervical nerve root injury commonly leads to radicular pain. Normal sensation relies on regulation of extracellular glutamate in the spinal cord by glutamate transporters. The goal of this study was to define the temporal response of spinal glutamate transporters (glial glutamate transporter 1 [GLT-1], glutamate-aspartate transporter [GLAST], and excitatory amino acid carrier 1) following nerve root compressions that do or do not produce sensitivity in the rat and to evaluate the role of glutamate uptake in radicular pain by using ceftriaxone to upregulate GLT-1. Compression was applied to the C7 nerve root. Spinal glutamate transporter expression was evaluated at days 1 and 7. In a separate study, rats underwent a painful root compression and were treated with ceftriaxone or the vehicle saline. Glial glutamate transporter expression, astrocytic activation (glial fibrillary acidic protein [GFAP]), and neuronal excitability were assessed at day 7. Both studies measured behavioral sensitivity for 7 days after injury. Spinal GLT-1 significantly decreased (P < 0.04) and spinal GLAST significantly increased (P = 0.036) at day 7 after a root injury that also produced sensitivity to both mechanical and thermal stimuli. Within 1 day after ceftriaxone treatment (day 2), mechanical allodynia began to decrease; both mechanical allodynia and thermal hyperalgesia were attenuated (P < 0.006) by day 7. Ceftriaxone also reduced (P < 0.024) spinal GFAP and GLAST expression, and neuronal hyperexcitability in the spinal dorsal horn, restoring the proportion of spinal neurons classified as wide dynamic range to that of normal. These findings suggest that nerve root-mediated pain is maintained jointly by spinal astrocytic reactivity and neuronal hyperexcitability and that these spinal modifications are associated with reduced glutamate uptake by GLT-1.

Level II, prospective observational cohort study.

Nerve root compression induces persistent behavioral hypersensitivity and spinal glial reactivity. Viscoelastic properties of neural tissues suggest that physiologic outcomes may depend on the duration of an applied nerve root compression. This study evaluated the time-dependent properties of the root under compression in the context of pain-related behavioral and physiologic outcomes. The decrease in applied load measured by load relaxation under compression was quantified for rat cervical (C6-C8) roots in situ for durations of 30 sec, 3 min, or 15 min (n ¼ 6). Immediately following compression, the change in the root width relative to its original width was quantified as a measure of its structural recovery. Both load relaxation and structural recovery were significantly ( p < 0.05) correlated with duration of compression. After 30 sec of compression, load relaxed by 22 AE 10%; increasing to 36 AE 18% and 56 AE 20% at 3 and 15 min, respectively. Following 30 sec, 3 min, and 15 min of compression, the root recovered to 91 AE 5%, 88 AE 5 and 72 AE 13% of its original width, respectively. A companion in vivo study imposed these same compression durations and sham procedures to the C7 root to evaluate pain symptoms and spinal glial reactivity. Allodynia was assessed for 7 days to measure behavioral sensitivity. Immunohistochemistry and quantitative densitometry detected GFAP and OX-42 in the dorsal horn at day 7. Significant correlations were detected between compression duration and allodynia ( p < 0.03), and astrocyte and microglial activation ( p < 0.01). These biomechanical and glial results imply that a similar duration of compression may modulate both sustained pain and spinal glial reactivity.

3.

Propensity score matching (PSM) is a commonly used statistical method in orthopedic surgery research that accomplishes the removal of confounding bias from observational cohorts where the benefit of randomization is not possible. An alternative to multiple regression analysis, PSM attempts to reduce the effects of confounders by matching already treated subjects with control subjects who exhibit a similar propensity for treatment based on preexisting covariates that influence treatment selection. It, therefore, establishes a new control group by discarding outlier control subjects. This new control group reduces the unwanted influences of covariates, allowing for proper measurement of the intended variable. An example from orthopedic spine literature is discussed to illustrate how PSM may be applied in practice. PSM is uniquely valuable in its utility and simplicity, but it is limited in that it requires the removal of data and works primarily on binary treatments. In addition to matching, the propensity score can be used for stratification, covariate adjustments, and inverse probability of treatment weighting, but these topics are outside the scope of this paper. Personnel in the orthopedic field would benefit from learning about the function and application of this method given its common use in the orthopedic literature.

Study Design. Retrospective comparative study. Objective. The purpose of this study was to investigate whether preoperative depressive symptoms, measured by mental component score of the Short Form-12 survey (MCS-12), influence patient-reported outcome measurements (PROMs) following an anterior cervical discectomy and fusion (ACDF) surgery for cervical degeneration. Summary of Background Data. There is a paucity of literature regarding preoperative depression and PROMs following ACDF surgery for cervical degenerative disease. Methods. Patients who underwent an ACDF for degenerative cervical pathology were identified. A score of 45.6 on the MCS-12 was used as the threshold for depression symptoms, and patients were divided into two groups based on this value: depression (MCS-12 ≤45.6) and nondepression (MCS-12 >45.6) groups. Outcomes including Neck Disability Index (NDI), physical component score of the Short Form-12 survey (PCS-12), and Visual Analogue Scale Neck (VAS Neck), and Arm (VAS Arm) pain scores were evaluated using independent sample t test, recovery ratios, percentage of patients reaching the minimum clinically important difference, and multiple linear regression – controlling for factors such as age, sex, and BMI. Results. The depression group was found to have significantly worse baseline pain and disability than the nondepression group in NDI (P < 0.001), VAS Neck pain (P < 0.001), and VAS Arm pain (P < 0.001) scores. Postoperatively, both groups improved to a similar amount with surgery based on the recovery ratio analysis. The depression group continued to have worse scores than the nondepression group in NDI (P = 0.010), PCS-12 (P = 0.026), and VAS Arm pain (P = 0.001) scores. Depression was not a significant predictor of change in any PROMs based on regression analysis. Conclusion. Patients who presented with preoperative depression reported more pain and disability symptoms preoperatively and postoperatively; however, both groups achieved similar degrees of improvement. Level of Evidence: 3

Object Cervical radiculopathy is often attributed to cervical nerve root injury, which induces extensive degeneration and reduced axonal flow in primary afferents. Riluzole inhibits neuro-excitotoxicity in animal models of neural injury. The authors undertook this study to evaluate the antinociceptive and neuroprotective properties of riluzole in a rat model of painful nerve root compression. Methods A single dose of riluzole (3 mg/kg) was administered intraperitoneally at Day 1 after a painful nerve root injury. Mechanical allodynia and thermal hyperalgesia were evaluated for 7 days after injury. At Day 7, the spinal cord at the C-7 level and the adjacent nerve roots were harvested from a subgroup of rats for immunohistochemical evaluation. Nerve roots were labeled for NF200, CGRP, and IB4 to assess the morphology of myelinated, peptidergic, and nonpeptidergic axons, respectively. Spinal cord sections were labeled for the neuropeptide CGRP and the glutamate transporter GLT-1 to evaluate their expression in the dorsal horn. In a separate group of rats, electrophysiological recordings were made in the dorsal horn. Evoked action potentials were identified by recording extracellular potentials while applying mechanical stimuli to the forepaw. Results Even though riluzole was administered after the onset of behavioral sensitivity at Day 1, its administration resulted in immediate resolution of mechanical allodynia and thermal hyperalgesia (p < 0.045), and these effects were maintained for the study duration. At Day 7, axons labeled for NF200, CGRP, and IB4 in the compressed roots of animals that received riluzole treatment exhibited fewer axonal swellings than those from untreated animals. Riluzole also mitigated changes in the spinal distribution of CGRP and GLT-1 expression that is induced by a painful root compression, returning the spinal expression of both to sham levels. Riluzole also reduced neuronal excitability in the dorsal horn that normally develops by Day 7. The frequency of neuronal firing significantly increased (p < 0.045) after painful root compression, but riluzole treatment maintained neuronal firing at sham levels. Conclusions These findings suggest that early administration of riluzole is sufficient to mitigate nerve root–mediated pain by preventing development of neuronal dysfunction in the nerve root and the spinal cord.

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