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Changes in Dorsal Root Ganglion Gene Expression in Response to Spinal Cord Stimulation

Tilley, Dana M. PhD; Cedeño, David L. PhD; Kelley, Courtney A. BS; DeMaegd, Margaret BS; Benyamin, Ramsin MD; Vallejo, Ricardo MD, PhD

Regional Anesthesia & Pain Medicine: March/April 2017 - Volume 42 - Issue 2 - p 246–251
doi: 10.1097/AAP.0000000000000550
Chronic and Interventional Pain: Original Article

Background and Objectives: Spinal cord stimulation (SCS) has been shown to influence pain-related genes in the spinal cord directly under the stimulating electrodes. There is limited information regarding changes occurring at the dorsal root ganglion (DRG). This study evaluates gene expression in the DRG in response to SCS therapy.

Methods: Rats were randomized into experimental or control groups (n = 6 per group). Experimental animals underwent spared-nerve injury, implantation of lead, and continuous SCS (72 hours). Behavioral assessment for mechanical hyperalgesia was conducted to compare responses after injury and treatment. Ipsilateral DRG tissue was collected, and gene expression quantified for interleukin 1b (IL-1b), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), GABA B receptor 1 (GABAbr1), substance P (subP), Integrin alpha M (ITGAM), sodium/potassium ATP-ase (Na/K ATPase), fos proto-oncogene (cFOS), serotonin receptor 3A (5HT3r), galanin (Gal), vasoactive intestinal peptide (VIP), neuropeptide Y (NpY), glial fibrillary acidic protein (GFAP), and brain derived neurotropic factor (BDNF) via quantitative polymerase chain reaction. Statistical significance was established using analysis of variance (ANOVA), independent t tests, and Pearson correlation tests.

Results: Expression of IL-1b and IL-6 was reversed following SCS therapy relative to the increase caused by the injury model. Both GABAbr1 and Na/K ATPase were significantly up-regulated upon implantation of the lead, and SCS therapy reversed their expression to within control levels. Pearson correlation analyses reveal that GABAbr1 and Na/K ATPase expression was dependent on the stimulating current intensity.

Conclusions: Spinal cord stimulation modulates expression of key pain-related genes in the DRG. Specifically, SCS led to reversal of IL-1b and IL-6 expression induced by injury. Interleukin 6 expression was still significantly larger than in sham animals, which may correlate to residual sensitivity following continuous SCS treatment. In addition, expression of GABAbr1 and Na/K ATPase was down-regulated to within control levels following SCS and correlates with applied current.

From the *Basic Science Research, Millennium Pain Center, Bloomington; †School of Biological Sciences, Illinois State University, Normal; ‡Medical School, University of Illinois at Urbana–Champaign, Urbana; and §Department of Psychology, Illinois Wesleyan University, Bloomington, IL.

Accepted for publication October 26, 2016.

Address correspondence to: Ricardo Vallejo, MD, PhD, Millennium Pain Center, 1015 S Mercer Ave, Bloomington, IL 61701 (e-mail:

R.V. and R.B. have been paid consultants for Boston Scientific and Nevro Corporation.

Funding was provided by Millennium Pain Center and Boston Scientific Neuromodulation.

The authors declare no conflict of interest.

Copyright © 2017 by American Society of Regional Anesthesia and Pain Medicine.