Quantitative sensory phenotyping in chronic neuropathic pain patients treated with unilateral L4-dorsal root ganglion stimulation

Thomas Kinfe,Michael Buchfelder,Thomas L Yearwood,Thomas Randau,Andreas Stadlbauer,Christian Maihöfner,Shafqat R Chaudhry,Sajjad Muhammad,Nico Von Willebrand,Klemens Winder,Walter Magerl,Sascha Gravius,Nadine Gravius

doi:10.1186/s12967-020-02566-8

Abstract

BackgroundIn a previous study, we reported that selective dorsal root ganglion stimulation (DRGSTIM) at DRG level L4 promoted a favorable outcome for complex regional pain syndrome (CRPS) patients along with DRGSTIM-related changes of inflammatory biomarkers in blood and saliva. The impact on somatosensation is largely unknown. Herein, we assessed the quantitative sensory profile to quantify L4-DRGSTIM effects in CRPS patients.MethodsTwelve refractory CRPS patients (4 female; 8 male; mean age 69 ± 9 years) received standardized quantitative sensory testing (QST) protocol at baseline and after 3 months of unilateral L4-DRGSTIM assessing nociceptive and non-nociceptive thermal and mechanical sensitivity of the knee affected by CRPS and the contralateral non-painful knee area.ResultsAt baseline, CRPS subjects showed significantly increased thresholds for warmth, tactile and vibration detection (WDT, MDT and VDT) and exaggerated pain summation (WUR). After 3 months of unilateral L4-DRGSTIM all pain parameters exhibited trends towards normalization of sensitivity accumulating to a significant overall normalization for pain sensitivity (effect size: 0.91, p < 0.01), while with the one exception of WDT all non-nociceptive QST parameters remained unchanged. Overall change of non-nociceptive detection was negligible (effect size: 0.25, p > 0.40). Notably, reduction of pain summation (WUR) correlated significantly with pain reduction after 3 months of L4-DRGSTIM.ConclusionsSelective L4-DRGSTIM lowered ongoing pain in CRPS patients and evoked significant normalization in the pain domain of the somatosensory profile. Thermoreception and mechanoreception remained unchanged. However, larger randomized, sham-controlled trials are highly warranted to shed more light on effects and mechanisms of dorsal root ganglion stimulation on quantitative sensory characteristics.The study protocol was registered at the 15.11.2016 on German Register for Clinical Trials (DRKS ID 00011267).https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011267

Highlights

In a previous study, we reported that selective dorsal root ganglion stimulation (DRGSTIM) at DRG level L4 promoted a favorable outcome for complex regional pain syndrome (CRPS) patients along with D RGSTIM-related changes of inflammatory biomarkers in blood and saliva
Since we have recently found that principal component analysis revealed a communality of pressure pain threshold (PPT) and pain summation (WUR) [39] we added a tentative analysis of the combined normalized data
We found a meaningful clinical response and improved quantitative sensory testing (QST) parameters, with regard to circulating inflammatory mediators assessed in our previously published study, increased serum values of pro-inflammatory markers have been quantified pre- and post L4-DRGSTIM compared to healthy controls for HMGB-1, Tumor necrosis factor (TNF)-α, IL-6 and leptin

Summary

Introduction

We reported that selective dorsal root ganglion stimulation (DRGSTIM) at DRG level L4 promoted a favorable outcome for complex regional pain syndrome (CRPS) patients along with D RGSTIM-related changes of inflammatory biomarkers in blood and saliva. Published complex regional pain syndrome (CRPS) tonic spinal cord stimulation (SCS) trials reported a success rate between 40–50%, while randomized-controlled CRPS studies found an increased pain suppression rate using targeted sub-perceptional DRGSTIM varying between 50–70%. Additional transcriptome analysis of the L4-DRGSTIM treated CRPS patients revealed a distinct upregulated—downregulated pattern of genes associated with inflammatory circuits pivotal for the development of CRPS (cytokine activity, glucose hemostasis, innate immune response, metabolic processing, sensory perception of pain, chronic inflammatory signaling, cell chemotaxis and neural synaptic transmission, cell chemotaxis, cell–cell signaling, vasodilatation, immune cell proliferation, cartilage development, cytokine synthesis, lipid metabolic function, angiogenesis, blood pressure and response to mechanical stimuli) [5]. The predominantly applied SCS waveform represented conventional low-frequency SCS pattern, despite one study, in which high-frequency SCS (HFS) was utilized [9,10,11,12,13,14,15,16,17]

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Results

Discussion

Conclusion