Review of Opioid Sparing Interventional Pain Management Options and Techniques for Radiofrequency Ablations for Sacroiliac Joint Pain.

PURPOSE OF REVIEW: The goal of this clinical review was to provide an update about the existing treatment options and associated evidence for various radiofrequency ablation techniques for sacroiliac joint pain. An electronic literature search on radiofrequency for the treatment of sacroiliac joint pain was conducted using PubMed, NCBI and Google Scholar. The following search keywords were used: radiofrequency ablation (cooled, pulsed, conventional, bipolar, intra-articular), sacroiliac joint and sacroiliac pain. The search was limited to human subjects, English language and articles with available full text. The bibliographic sections of all manuscripts were further searched for additional relevant citations. The full text of the relevant articles was reviewed by all the authors. RECENT FINDINGS: Our study showed that radiofrequency ablation is a safe and effective treatment option that can be utilized to manage sacroiliac joint pain. It offers accessibility to the primary care physician, reduces office visits with "pain" as the primary complaint and provides the added benefit of acting as a non-opioid sparing means of analgesia.

Clinical Radiofrequency Ablation Outcomes of Combined Sensory Nerve Branch and Dorsal Entry Root Zone Complex Lesions for Sacroiliac Joint Complex Pain.

BACKGROUND: Chronic lower back pain (LBP) with or without leg pain (LP) is the most commonly reported anatomical site of pain among Canadian adults with chronic pain. A common cause for LBP and LP arises from dysfunction of the sacroiliac joint (SIJ) complex. When conventional medical management or rehabilitative efforts for SIJ-related LBP and LP fail to provide analgesia, pulsed radiofrequency (PRF) and/or radiofrequency ablation (RFA) of the dorsal entry root zone complex lesions (DREZC) and/or their more peripheral branches can also be a suitable means for treatment. Both PRF and RFA are interventional techniques that utilize heat to attenuate or ablate transmission of painful signals, respectively. The purpose of this chart review is to explore the clinical outcomes of patients experiencing SIJ-related pain who have undergone procedures with combined sensory nerve branch RFA and DREZC PRF lesions targeting the SIJ complex. METHODS: Following institutional review board approval, a retrospective chart review was performed from June 2018 to February 2021 for patients with LBP and/or LP refractory to physical rehabilitative efforts and medical management that underwent combined PRF and RF treatments for a diagnosis of SIJ complex pain. RF and PRF procedures were anatomically guided with the addition of sensory stimulation to ensure appropriate needle placement. Charts were reviewed for percentage of analgesia at final follow-up, duration of effect, degree of analgesia, patients' functional improvements, and changes in medication use patterns. RESULTS: Data was reviewed from 180 patients with LBP or LP who underwent combined PRF and RF treatments for a diagnosis of SIJ complex pain. The group consisted of 69 men and 111 women with a mean age of 59 years. All patients had lesions to their dorsal roots and/or branches (lumbar medial and sacral lateral), as determined using their pain profile as well as sensory stimulation. In the sample of 180 patients a total of 276 SIJs were treated over the period of data collection. Overall, 85.0% (n = 234) of procedures were considered successful with more than 50% analgesic relief at final follow-up. Of 234 successful outcomes, 110 reported ongoing analgesia (mean = 80.3% pain relief, SD ± 18.0) on the last date of follow up (mean = 53.2 days, SD ± 41.8) prior to being lost to follow-up. For patients not lost to follow-up, the mean amount of analgesia was reported to be 83.9% with an average duration of 86.3 days. Among all treatments, 6.9% (n = 19) provided no analgesic effect. Among the successful procedure outcomes, 54.4% (n = 150) reported increased activity/mobility, 24.3% (n = 67) reported improved sleep, 49.3% (n = 136) reported improved mood, and 11.6% (n = 32) reported decreased medication usage. Nine patients reported complications following the procedure. Complications included transient soreness, bruising, tenderness, myofascial pain, and two mild vagal responses without lasting sequelae. CONCLUSION: This review suggests that combined sensory nerve branch RFA and DREZC PRF lesions targeting the SIJ complex is a suitable intervention to treat SIJ-related LBP and/or LP refractory to physical rehabilitative efforts and medical management. Approximately 85% of these cases were successfully treated with the majority of patients report lasting analgesic effects with minimal complications, supporting the use of sensory stimulation-guided combined RF and PRF lesions for treatment of refractory SIJ complex pain.

Safety of Conventional and Pulsed Radiofrequency Lesions of the Dorsal Root Entry Zone Complex (DREZC) for Interventional Pain Management: A Systematic Review.

STUDY DESIGN: Systematic literature review. OBJECTIVE: The goal of this systematic review is to assess the clinical safety and potential complications of conventional and pulsed radiofrequency ablations targeting dorsal root entry zone complex (DREZC) components in the treatment of chronic pain. BACKGROUND: There is a growing popularity for the use of radiofrequency ablation (RFA) techniques targeting DREZC components by pain management physicians for an increasing variety of indications. To date, we lack a systematic review to describe the safety and the type of complications associated with these procedures. METHODS: This was a systematic literature review. This systematic search was limited to peer-reviewed literature using "radiofrequency ablation" as a search keyword using PubMed's database for manuscripts published between inception and December 2020. Abstracts that involved the application of radiofrequency currents, of any modality, to DREZC components for the treatment of pain were included for full-text review. Search was limited to original data describing clinical outcomes following RFA performed for pain indications only, involving the DREZC components outlined above, in human subjects, and written in English. The primary outcomes were complications associated with conventional RFA and pulsed radiofrequency ablation (PRF). Complications were categorized as type 1 (persistent neurological deficits or other serious adverse events, defined as any event that resulted in permanent of prolonged injury; type 2 (transient neuritis or neurological deficits, or other non-neurological non-minor adverse event); type 3 (minor adverse events (e.g., headache, soreness, bruising, etc.). RESULTS: Of the 62 selected manuscripts totaling 3157 patients, there were zero serious adverse events or persistent neurological deficits reported. A total of 36 (1.14%) transient neurological deficits, cases of transient neuritis, or non-minor adverse events like uncomplicated pneumothorax were reported. A total of 113 (3.58%) minor adverse events were reported (bruising, transient site soreness, headache). CONCLUSIONS: This systematic review indicates that the use of RFA lesion of the DREZC for interventional pain management is very safe. There were no serious adverse effects with a sizable sample of randomized controlled trial (RCT), prospective observational, and retrospective studies.

Pulsed Radiofrequency in Interventional Pain Management: Cellular and Molecular Mechanisms of Action - An Update and Review.

BACKGROUND: Pulsed radiofrequency (PRF) treatment uses low energy, short pulsations to modulate tissue characteristics. PRF treatment has been effective as an interventional pain management technique to treat a variety of chronic neuropathic pain (neuralgia) disorders, but a comprehensive review of its biological mechanism has not been updated in a decade. OBJECTIVES: In this literature review, we performed a literature search in PubMed to identify publications describing the mechanisms of action of pulsed radiofrequency for pain indications. STUDY DESIGN: Narrative literature review. METHODS: A systematic search was performed through PubMed from database inception to December 31, 2019, to identify all articles addressing the cellular or molecular mechanisms of action of PRF on neuropathic pain. The search terms "pulsed radiofrequency" and "pulsed radiofrequency mechanisms" were used. Cellular and molecular mechanisms of PRF interventions were subdivided into 3 broad categories: nociceptive signalling, immune activity, and synaptic function. A total of 20 publications were identified for inclusion in this updated review. RESULTS: It was found that pulsed radiofrequency impacts many different biological pathways involved in the modulation of chronic neuropathic pain (neuralgia). With regards to nociceptive signalling, PRF treatment modulates ion channels (Na/K ATPase, HCN, P2X3), CGRP, neurotransmitters (aspartate, citrulline, M-ENK, glutamate), postsynaptic receptors (AMPA-R, GABA-B), and synaptic function (KCC2). PRF treatment also modulates immune activity, including microglial markers (CD3, CD56, Iba1), inflammatory cytokines (IL-6, IL-17, IRF8, IFN-g, TNFa), and intracellular proteins implicated in immune mediated neuropathic pain (BDNF, b-catenin, JNK, p38, ERK1/2). LIMITATIONS: This review is primarily limited by the diverse data sets that needed to be collated and correlated, as no study was comprehensive in addressing all markers, cytokines, pathways, neurotransmitters, ion channels, proteins, genes, and gene expression changes, along with their clinical outcomes concurrently. As such, the interplay of these individual pathways and mechanisms and their isolated effects on efficacy of PRF cannot be concluded. Rather, the large majority of findings can be seen as associations instead of definitive causal relationships to clinical outcomes. CONCLUSIONS: Herein describes a clinically relevant collated update describing the cellular and molecular mechanisms of action of PRF for pain management.

A Literature Review of Dorsal Root Entry Zone Complex (DREZC) Lesions: Integration of Translational Data for an Evolution to More Accurate Nomenclature.

The purpose of this translational review was to provide evidence to support the natural evolution of the nomenclature of neuromodulatory and neuroablative radiofrequency lesions for pain management from lesions of individualized components of the linear dorsal afferent pathway to "Dorsal Root Entry Zone Complex (DREZC) lesions." Literature review was performed to collate anatomic and procedural data and correlate these data to clinical outcomes. There is ample evidence that the individual components of the DREZC (the dorsal rami and its branches, the dorsal root ganglia, the dorsal rootlets, and the dorsal root entry zone) vary dramatically between vertebral levels and individual patients. Procedurally, fluoroscopy, the most commonly utilized technology is a 2-dimensional x-ray-based technology without the ability to accurately locate any one component of the DREZC dorsal afferent pathway, which results in clinical inaccuracies when naming each lesion. Despite the inherent anatomic variability and these procedural limitations, the expected poor clinical outcomes that might follow such nomenclature inaccuracies have not been shown to be prominent, likely because these are all lesions of the same anatomically linear sensory pathway, the DREZC, whereby a lesion in any one part of the pathway would be expected to interrupt sensory transmission of pain to all subsequent more proximal segments. Given that the common clinically available tools (fluoroscopy) are inaccurate to localize each component of the DREZC, it would be inappropriate to continue to erroneously refer to these lesions as lesions of individual components, when the more accurate "DREZC lesions" designation can be utilized. Hence, to avoid inaccuracies in nomenclature and until more accurate imaging technology is commonly utilized, the evidence herein supports the proposed change to this more sensitive and inclusive nomenclature, "DREZC lesions."

Naltrexone's Impact on Cancer Progression and Mortality: A Systematic Review of Studies in Humans, Animal Models, and Cell Cultures.

BACKGROUND: Naltrexone (NTX) is an opioid antagonist traditionally used as a treatment for alcohol and opioid use disorders, but various studies have documented its involvement in cancer progression, exploring possible anticancer potential, when administered at high doses or as low dose naltrexone (LDN). Herein we present a systematic review of cancer-related outcomes from case reports, clinical trials, and retrospective and prospective studies conducted using cell cultures, animal models, and human subjects receiving NTX/LDN. METHODS: A systematic search of NTX in cancer therapy was conducted. Outcomes including tumor size and number, latency to tumor development, survival duration, progression of disease, and scan results were assessed in clinical and animal studies, and cell number was used as the outcome measure of culture studies. RESULTS: Several case reports demonstrate notable survival durations and metastatic resolutions in patients with late stage cancer when administered an average LDN dose of 3-5 mg/day. Animal and cell culture studies suggest an overarching principle of NTX involvement in cancer pharmacophysiology, suggesting that high doses and continuous administration can foster cancer progression, whereas low doses and intermittent treatment may hinder cell proliferation, impede tumorigenesis, and have potential anticancer efficacy. CONCLUSION: This review emphasizes the value of potential future research on NTX in cancer therapy, and warrants need for a better understanding of underlying mechanisms. Future controlled studies with more robust sample sizes, particularly in humans, are needed to fully elucidate its potential in cancer therapy.

Systematic Review of the Use of Intravenous Ketamine for Fibromyalgia.

Background: Fibromyalgia, a complex disorder that affects 1% to 5% of the population, presents as widespread chronic musculoskeletal pain without physical or laboratory signs of any specific pathologic process. The mechanism, while still being explored, suggests central sensitization and disordered pain regulation at the spinal cord and supraspinal levels, with a resulting imbalance between excitation and inhibition that may alter central nervous system nociceptive processing. Nociceptive hypersensitivity results from activity of the N-methyl-D-aspartate receptor (NMDAR)-mediated glutamatergic synaptic transmission in the spinal cord and brain. Because ketamine, an NMDAR antagonist, may reduce induction of synaptic plasticity and maintenance of chronic pain states, the study of its use in intravenous form to treat fibromyalgia has increased. Methods: We conducted a literature search with the objectives of examining the effect of intravenous ketamine administration on pain relief, identifying side effects, and highlighting the need for clinical studies to evaluate ketamine infusion treatment protocols for patients with fibromyalgia. We used the keywords "fibromyalgia," "chronic pain," "ketamine," "intravenous," and "infusion" and found 7 publications that included 118 patients with fibromyalgia who met inclusion criteria. Results: Clinical studies revealed a short-term reduction-only for a few hours after the infusions-in self-reported pain intensity with single, low-dose, intravenous ketamine infusions, likely attributable to nociception-dependent central sensitization in fibromyalgia via NMDAR blockade. Case studies suggest that increases in the total dose of ketamine and longer, more frequent infusions may be associated with more effective pain relief and longer-lasting analgesia. Another neurotransmitter release may be contributing to this outcome. Conclusion: This systematic review suggests a dose response, indicating potential efficacy of intravenous ketamine in the treatment of fibromyalgia.