Selective L4 Dorsal Root Ganglion Stimulation Evokes Pain Relief and Changes of Inflammatory Markers: Part I Profiling of Saliva and Serum Molecular Patterns

Gravius, Nadine; Chaudhry, Shafqat Rasul; Muhammad, Sajjad; Boström, Azize; Gravius, Sascha; Randau, Thomas M.; Scheele, Dirk; Westhofen, P.; Kruppenbacher, J. P.; Stoffel‐Wagner, Birgit; Maier, Christian; Weidlich, Anna; Yearwood, Thomas; Chakravarthy, Krishnan; Kramer, Jeffery M.; Hurlemann, René; Kinfe, Thomas M.

doi:10.1111/ner.12866

Cited by 31 publications

(48 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with previously reported observational cohort and randomized-controlled trials we have most recently demonstrated that unilateral selective L4-dorsal root ganglion stimulation (L4-DRG STIM ) evoked pain relief in complex regional pain syndrome patients (CRPS) and improved functional capacity as well [1–4]. In addition, we observed changes of peripheral circulating inflammatory mediators in different biofluids (saliva and serum).…”

Section: Introductionsupporting

confidence: 89%

“…Table 1 summarizes baseline characteristics and applied DRG stimulation pattern and Table 2 the peripheral levels of inflammatory mediators assessed in our previous study [1].…”

Section: Resultsmentioning

confidence: 99%

“…Peripheral pro-inflammatory IL-1β was significantly elevated pre-L4 DRG STIM , but not post-L4 DRG STIM , while anti-inflammatory IL-10 also declined after 3 months of unilateral L4-DRG STIM with oxytocin from saliva increased after 3 months L4-DRG STIM. Members of the adipokine superfamily associated with metabolic disorders such as ghrelin and adiponectin remained unchanged [1].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Unilateral L4-dorsal root ganglion stimulation evokes pain relief in chronic neuropathic postsurgical knee pain and changes of inflammatory markers: part II whole transcriptome profiling

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background In our recent clinical trial, increased peripheral concentrations of pro-inflammatory molecular mediators were determined in complex regional pain syndrome (CRPS) patients. After 3 months adjunctive unilateral, selective L4 dorsal root ganglion stimulation (L4-DRG STIM ), significantly decreased serum IL-10 and increased saliva oxytocin levels were assessed along with an improved pain and functional state. The current study extended molecular profiling towards gene expression analysis of genes known to be involved in the gonadotropin releasing hormone receptor and neuroinflammatory (cytokines/chemokines) signaling pathways. Methods Blood samples were collected from 12 CRPS patients for whole-transcriptome profiling in order to assay 18,845 inflammation-associated genes from frozen blood at baseline and after 3 months L4-DRG STIM using PANTHER™ pathway enrichment analysis tool. Results Pathway enrichment analyses tools (GOrilla™ and PANTHER™) showed predominant involvement of inflammation mediated by chemokines/cytokines and gonadotropin releasing hormone receptor pathways. Further, screening of differentially regulated genes showed changes in innate immune response related genes. Transcriptomic analysis showed that 21 genes (predominantly immunoinflammatory) were significantly changed after L4-DRG STIM . Seven genes including TLR1 , FFAR2 , IL1RAP , ILRN , C5 , PKB and IL18 were down regulated and fourteen genes including CXCL2, CCL11, IL36G, CRP, SCGB1A1, IL - 17F, TNFRSF4, PLA2G2A, CREB3L3, ADAMTS12, IL1F10, NOX1, CHIA and BDKRB1 were upregulated. Conclusions In our sub-group analysis of L4-DRG STIM treated CRPS patients, we found either upregulated or downregulated genes involved in immunoinflammatory circuits relevant for the pathophysiology of CRPS indicating a possible relation. However, large biobank-based approaches are recommended to establish genetic phenotyping as a quantitative outcome measure in CRPS patients. Trial registration 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

show abstract

Section: Introductionsupporting

confidence: 89%

“…Table 1 summarizes baseline characteristics and applied DRG stimulation pattern and Table 2 the peripheral levels of inflammatory mediators assessed in our previous study [1].…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Unilateral L4-dorsal root ganglion stimulation evokes pain relief in chronic neuropathic postsurgical knee pain and changes of inflammatory markers: part II whole transcriptome profiling

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…The end result of electrical stimulation on the DRG neurons is to stabilize and decrease hyperexcitability (15). In addition, to our knowledge, all in vitro and in vivo animal studies have shown that DRG stimulation has positive effects on pain-related outcomes without causing any inflammation or DRG tissue damage and may actually be antiinflammatory (16,17).…”

Section: Introductionmentioning

confidence: 99%

Effectiveness and Safety of Dorsal Root Ganglion Stimulation for the Treatment of Chronic Pain: A Pooled Analysis

Huygen

Kallewaard

Nijhuis

et al. 2020

Neuromodulation: Technology at the Neural Interface

View full text Add to dashboard Cite

Introduction Since it became available in the mid‐2010s, dorsal root ganglion (DRG) stimulation has become part of the armamentarium to treat chronic pain. To date, one randomized controlled trial, and several studies of moderate sample size and various etiologies have been published on this topic. We conducted a pooled analysis to investigate the generalizability of individual studies and to identify differences in outcome between chronic pain etiologic subgroups and/or pain location. Materials and Methods One prospective, randomized comparative trial and six prospective, single‐arm, observational studies were identified that met pre‐defined acceptance criteria. Pain scores and patient‐reported outcome (PRO) measures were weighted by study sample sizes and pooled. Safety data are reported in aggregate form. Results Our analysis included 217 patients with a permanent implant at 12‐month follow‐up. Analysis of pooled data showed an overall weighted mean pain score of 3.4, with 63% of patients reporting ≥50% pain relief. Effectiveness sub‐analyses in CRPS‐I, causalgia, and back pain resulted in a mean reduction in pain intensity of 4.9, 4.6, and 3.9 points, respectively. Our pooled analysis showed a pain score for primary affected region ranging from 1.7 (groin) to 3.0 (buttocks) and responder rates of 80% for foot and groin, 75% for leg, and 70% for back. A substantial improvement in all PROs was observed at 12 months. The most commonly reported procedural or device complications were pain at the IPG pocket site, lead fracture, lead migration, and infection. Conclusions DRG stimulation is an effective and safe therapy for various etiologies of chronic pain.

show abstract

“…A second possible explanation for the differences in habituation is that there are multiple, synergistic effects resulting from DRG stimulation that produce a more robust change in the chronic pain state, such as the impact of DRG stimulation on the inflammatory reflex. 7 Third, it was previously shown that DRG stimulation provided greater improvement in psychological disposition versus tonic SCS, 5 possibly through modulation by DRG stimulation of the medial pain pathway associated with the emotional aspects of pain. 20 Alleviating the adverse psychological factors associated with pain could enhance long-term outcomes.…”

Section: Discussionmentioning

confidence: 99%

Therapy Habituation at 12 Months: Spinal Cord Stimulation Versus Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome Type I and II

Levy

Mekhail

Kramer

et al. 2020

The Journal of Pain

View full text Add to dashboard Cite

Selective L4 Dorsal Root Ganglion Stimulation Evokes Pain Relief and Changes of Inflammatory Markers: Part I Profiling of Saliva and Serum Molecular Patterns

Cited by 31 publications

References 47 publications

Unilateral L4-dorsal root ganglion stimulation evokes pain relief in chronic neuropathic postsurgical knee pain and changes of inflammatory markers: part II whole transcriptome profiling

Unilateral L4-dorsal root ganglion stimulation evokes pain relief in chronic neuropathic postsurgical knee pain and changes of inflammatory markers: part II whole transcriptome profiling

Effectiveness and Safety of Dorsal Root Ganglion Stimulation for the Treatment of Chronic Pain: A Pooled Analysis

Therapy Habituation at 12 Months: Spinal Cord Stimulation Versus Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome Type I and II

Contact Info

Product

Resources

About