Intermittent Dorsal Root Ganglion Stimulation Is as Efficacious as Standard Continuous Dosing in Treating Chronic Pain: Results From a Randomized Controlled Feasibility Trial

Primary sensory neurons of the dorsal root ganglion (DRG) respond and relay sensations that are felt, such as those for touch, pain, temperature, itch, and more. The ability to discriminate between the various types of stimuli is reflected by the existence of specialized DRG neurons tuned to respond to specific stimuli. Because of this, a comprehensive classification of DRG neurons is critical for determining exactly how somatosensation works and for providing insights into cell types involved during chronic pain. This article reviews the recent advances in unbiased classification of molecular types of DRG neurons in the perspective of known functions as well as predicted functions based on gene expression profiles. The data show that sensory neurons are organized in a basal structure of three cold-sensitive neuron types, five mechano-heat sensitive nociceptor types, four A-Low threshold mechanoreceptor types, five itch-mechano-heat–sensitive nociceptor types and a single C–low-threshold mechanoreceptor type with a strong relation between molecular neuron types and functional types. As a general feature, each neuron type displays a unique and predicable response profile; at the same time, most neuron types convey multiple modalities and intensities. Therefore, sensation is likely determined by the summation of ensembles of active primary afferent types. The new classification scheme will be instructive in determining the exact cellular and molecular mechanisms underlying somatosensation, facilitating the development of rational strategies to identify causes for chronic pain.

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Dorsal root ganglion stimulation lead fractures: potential mechanisms and ways to avoid

BMJ Case Reports ◽

10.1136/bcr-2020-241353 ◽

2021 ◽

Vol 14 (5) ◽

pp. e241353

Author(s):

Gaurav Chauhan ◽

Brandon I Roth ◽

Nagy Mekhail

Keyword(s):

Spinal Cord ◽

Chronic Pain ◽

Case Report ◽

Dorsal Root Ganglion ◽

Dorsal Root ◽

Unusual Case ◽

Pain Syndrome ◽

Structural Instability ◽

Probable Mechanism ◽

Lead Fracture

Dorsal root ganglion stimulation (DRGS) therapy is a rapidly emerging tool being used by pain physicians in the treatment of chronic pain. Complex regional pain syndrome (CRPS), a debilitating disease whose mechanism is still has yet to be fully elucidated, is a common pathology targeted by DRGS therapy, often better results than traditional spinal cord stimulation. DRGS therapy, however, is not bereft of complications. Lead migration and fracture are two examples in particular that are among the most common of these complications. The authors report an unusual case of lost efficacy due to lead fractures in patients with CRPS treated with DRGS. The case report narrates identification, management and probable mechanism of DRGS lead fracture. The structural instability of DRGS leads can yield distressing symptoms at any point during the therapy, and physicians should be cognisant of the complications of DRGS therapy.

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

Neuromodulation Technology at the Neural Interface ◽

10.1111/ner.13074 ◽

2019 ◽

Vol 23 (2) ◽

pp. 213-221 ◽

Cited By ~ 7

Author(s):

Frank J.P.M. Huygen ◽

Jan Willem Kallewaard ◽

Harold Nijhuis ◽

Liong Liem ◽

Jan Vesper ◽

...

Keyword(s):

Chronic Pain ◽

Dorsal Root Ganglion ◽

Dorsal Root ◽

Pooled Analysis

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Noncoding RNAs

Anesthesiology ◽

10.1097/aln.0000000000000265 ◽

2014 ◽

Vol 121 (2) ◽

pp. 409-417 ◽

Cited By ~ 56

Author(s):

Brianna Marie Lutz ◽

Alex Bekker ◽

Yuan-Xiang Tao

Keyword(s):

Chronic Pain ◽

Dorsal Root Ganglion ◽

Antisense Rna ◽

Dorsal Root ◽

Molecular Mechanisms ◽

Noncoding Rnas ◽

Current Evidence ◽

Noxious Stimuli ◽

Chronic Pain Conditions ◽

Novel Therapeutic Strategies

Abstract Chronic pain, a common clinical symptom, is often treated inadequately or ineffectively in part due to the incomplete understanding of molecular mechanisms that initiate and maintain this disorder. Newly identified noncoding RNAs govern gene expression. Recent studies have shown that peripheral noxious stimuli drive expressional changes in noncoding RNAs and that these changes are associated with pain hypersensitivity under chronic pain conditions. This review first presents current evidence for the peripheral inflammation/nerve injury–induced change in the expression of two types of noncoding RNAs, microRNAs, and Kcna2 antisense RNA, in pain-related regions, particularly in the dorsal root ganglion. The authors then discuss how peripheral noxious stimuli induce such changes. The authors finally explore potential mechanisms of how expressional changes in dorsal root ganglion microRNAs and Kcna2 antisense RNA contribute to the development and maintenance of chronic pain. An understanding of these mechanisms may propose novel therapeutic strategies for preventing and/or treating chronic pain.

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Nerve Injury-Induced Chronic Pain Is Associated with Persistent DNA Methylation Reprogramming in Dorsal Root Ganglion

Journal of Neuroscience ◽

10.1523/jneurosci.2616-17.2018 ◽

2018 ◽

Vol 38 (27) ◽

pp. 6090-6101 ◽

Cited By ~ 22

Author(s):

Judit Garriga ◽

Geoffroy Laumet ◽

Shao-Rui Chen ◽

Yuhao Zhang ◽

Jozef Madzo ◽

...

Keyword(s):

Dna Methylation ◽

Chronic Pain ◽

Dorsal Root Ganglion ◽

Nerve Injury ◽

Dorsal Root

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Randomized controlled trials between dorsal root ganglion thermal radiofrequency, pulsed radiofrequency and steroids for the management of intractable metastatic back pain in thoracic vertebral body

British Journal of Pain ◽

10.1177/2049463720942538 ◽

2020 ◽

pp. 204946372094253

Author(s):

Sherry Nabil Fanous ◽

Emad Gerges Saleh ◽

Ekramy Mansour Abd Elghafar ◽

Hossam Zarif Ghobrial

Keyword(s):

Dorsal Root Ganglion ◽

Dorsal Root ◽

Oral Morphine ◽

Good Alternative ◽

Drop Out ◽

Pulsed Radiofrequency ◽

Vertebral Metastasis ◽

Randomized Controlled ◽

Augmentation Techniques ◽

Axial Pain

Background: Bone metastasis is a complication of various cancers causing severe pain. The current modalities for the treatment of metastatic axial pain include pharmacological, surgical and vertebral augmentation techniques, each of which has its own challenges. Objectives: To evaluate the effectiveness of pulsed radiofrequency (PRF), thermal radiofrequency (RF) and steroids on dorsal root ganglion (DRG) in patients with thoracic axial pain due to vertebral metastasis. Methods: In this randomized controlled prospective study, 140 patients were assessed for eligibility, of which only 69 fulfilled the criteria. Patients were randomly divided into three equal groups, PRF, RF and steroid. Results: During the assessment of pain using Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), Opioid consumption using oral Morphine Equivalence (OME) and Analgesic Quantification Algorithm (AQA) – at baseline, 1 week, 1 month and 3 months – 81 patients were assessed for final eligibility, of which 12 were excluded before intervention due to drop-out. The remaining 69 were randomized (mean age: 53.87 ± 10.55, 55.78 ± 7.34 and 59.39 ± 13.72) for PRF, RF and steroid, respectively with no statistical difference. VAS% and ODI% decreased significantly at 3 months in RF group ( p <0.001, 0.014, respectively), as did the AQA ( p <0.027). Steroid group was the worst. Discussion: RF on DRG is the main stay for controlling intractable metastatic pain. PRF is a good alternative.

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A Systematic Literature Review of Dorsal Root Ganglion Neurostimulation for the Treatment of Pain

Pain Medicine ◽

10.1093/pm/pnaa005 ◽

2020 ◽

Vol 21 (8) ◽

pp. 1581-1589 ◽

Cited By ~ 2

Author(s):

Timothy R Deer ◽

Corey W Hunter ◽

Pankaj Mehta ◽

Dawood Sayed ◽

Jay S Grider ◽

...

Keyword(s):

Dorsal Root Ganglion ◽

Literature Review ◽

Systematic Literature Review ◽

Dorsal Root ◽

Task Force ◽

Controlled Trial ◽

Risk Of Bias ◽

Level Of Evidence ◽

Bias Assessment ◽

Randomized Controlled

Abstract Objective To conduct a systematic literature review of dorsal root ganglion (DRG) stimulation for pain. Design Grade the evidence for DRG stimulation. Methods An international, interdisciplinary work group conducted a literature search for DRG stimulation. Abstracts were reviewed to select studies for grading. General inclusion criteria were prospective trials (randomized controlled trials and observational studies) that were not part of a larger or previously reported group. Excluded studies were retrospective, too small, or existed only as abstracts. Studies were graded using the modified Interventional Pain Management Techniques–Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria. Results DRG stimulation has Level II evidence (moderate) based upon one high-quality pivotal randomized controlled trial and two lower-quality studies. Conclusions Moderate-level evidence supports DRG stimulation for treating chronic focal neuropathic pain and complex regional pain syndrome.

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Activation of STAT3-mediated CXCL12 up-regulation in the dorsal root ganglion contributes to oxaliplatin-induced chronic pain

Molecular Pain ◽

10.1177/1744806917747425 ◽

2017 ◽

Vol 13 ◽

pp. 174480691774742 ◽

Cited By ~ 11

Author(s):

Yong-Yong Li ◽

He Li ◽

Ze-Long Liu ◽

Qiong Li ◽

Hua-Wen Qiu ◽

...

Keyword(s):

Chronic Pain ◽

Dorsal Root Ganglion ◽

Dorsal Root

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Perspectives in Pain Research 2014: Neuroinflammation and glial cell activation: The cause of transition from acute to chronic pain?

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2014.10.002 ◽

2015 ◽

Vol 6 (1) ◽

pp. 3-6 ◽

Cited By ~ 21

Author(s):

Brian E. Cairns ◽

Lars Arendt-Nielsen ◽

Paola Sacerdote

Keyword(s):

Spinal Cord ◽

Chronic Pain ◽

Dorsal Root Ganglion ◽

Glial Cell ◽

Schwann Cells ◽

Glial Cells ◽

Proinflammatory Cytokines ◽

Immune Cells ◽

Dorsal Root ◽

Satellite Glial Cells

AbstractBackgroundIt is unknown why an acute pain condition under various circumstances can transition into a chronic pain condition.There has been a shift towards neuroinflammation and hence glial cell activations specifically in the dorsal root ganglion and spinal cord as a mechanism possibly driving the transition to chronic pain. This has led to a focus on non-neuronal cells in the peripheral and central nervous system. Besides infiltrating macrophages, Schwann cells and satellite glial cells release cytokines and therefore important mechanisms in the maintenance of pain. Activated Schwann cells, satellite glial cells, microglia, and astrocytes may contribute to pain sensitivity by releasing cytokines leading to altered neuronal function in the direction of sensitisation.Aims of this perspective paper1) Highlight the complex but important recent achievement in the area of neuroinflammation and pain at spinal cord level and in the dorsal root ganglion.2) Encourage further research which hopefully may provide better understanding of new key elements driving the transition from acute to chronic pain.Recent results in the area of neuroinflammation and painFollowing a sciatic nerve injury, local macrophages, and Schwann cells trigger an immune response immediately followed by recruitment of blood-derived immune cells. Schwann cells, active resident, and infiltrating macrophages release proinflammatory cytokines. Proinflammatory cytokines contribute to axonal damage and also stimulate spontaneous nociceptor activity. This results in activation of satellite glial cells leading to an immune response in the dorsal root ganglia driven by macrophages, lymphocytes and satellite cells. The anterograde signalling progresses centrally to activate spinal microglia with possible up regulation of glial-derived proinflammatory/pronociceptive mediators.An important aspect is extrasegmental spreading sensitisation where bilateral elevations in TNF-α, IL-6, and IL-10 are found in dorsal root ganglion in neuropathic models. Similarly in inflammatory pain models, bilateral up regulation occurs for TNF-α, IL-1 β, and p38 MAPK. Bilateral alterations in cytokine levels in the DRG and spinal cord may underlie the spread of pain to the uninjured side.An important aspect is how the opioids may interact with immune cells as opioid receptors are expressed by peripheral immune cells and thus can induce immune signaling changes. Furthermore, opioids may stimulate microglia cells to produce proinflammatory cytokines such as IL-1.ConclusionsThe present perspective paper indicates that neuroinflammation and the associated release of pro-inflammatory cytokines in dorsal root ganglion and at the spinal cord contribute to the transition from acute to chronic pain. Neuroinflammatory changes have not only been identified in the spinal cord and brainstem, but more recently, in the sensory ganglia and in the nerves as well. The glial cell activation may be responsible for contralateral spreading and possible widespread sensitisation.ImplicationsCommunication between glia and neurons is proposed to be a critical component of neuroinflammatory changes that may lead to chronic pain. Sensory ganglia neurons are surrounded by satellite glial cells but how communication between the cells contributes to altered pain sensitivity is still unknown. Better understanding may lead to new possibilities for (1) preventing development of chronic pain and (2) better pain management.

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