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OBJECTIVES: Lumbar spine surgery is a common procedure for treating disabling spine-related pain. In recent decades, both the number and cost of spine surgeries have increased despite technological advances and modification in surgical technique. For those patients that have continued uncontrolled back and/or lower extremity pain following lumbar spine surgery, spinal cord stimulation (SCS) has emerged as a viable treatment option. However, the impact of lumbar spine surgical history remains largely unstudied. Specifically, the current study considers the impact of number of prior lumbar spine surgeries on pain relief outcomes following SCS implantation. MATERIALS AND METHODS: We queried the electronic medical record of five separate pain practices for all patients who have undergone a SCS implant between January 1, 2017, and March 1, 2020. Inclusion criteria consisted of any patients with an SCS implant who underwent a prior lumbar spine surgery. The primary outcome was the mean calculated percentage pain relief in patients based on number of prior lumbar spine surgeries. RESULTS: There was a total of 1974 total SCS implant cases identified across five separate pain clinics. There was no difference in mean calculated pain relief in patients with one prior spine surgery versus those with two or more prior spine surgeries (28.2% vs. 25.8%, adjusted ß-coefficient -3.1, 95% CI -8.9 to 2.7, p = 0.290). Similarly, when analyzing number of spine surgeries as a continuous variable, there was no association between number of spine surgeries and calculated pain relief (adjusted ß-coefficient -1.5, 95% CI -4.0 to 1.1, p = 0.257). Additionally, after patients were stratified based on waveform, there was no association between number of prior lumbar spine surgeries (analyzed both as a categorical and continuous variable) and calculated percentage pain relief. CONCLUSIONS: This multicentered retrospective study found that there was no significant difference in pain scores in individuals who received SCS following one or more lumbar spine surgeries. Additionally, the waveform of the SCS device had no statistically significant impact on post-operative pain scores following one or more lumbar spine surgeries.
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PURPOSE: Evidence suggests that traditional low-frequency spinal cord stimulation (LF-SCS) reduces arterial blood pressure (BP) in patients with chronic pain and hypertension independent of improved pain symptoms. However, it remains unclear whether high-frequency spinal cord stimulation (HF-SCS) also lowers BP in chronic pain patients with hypertension. Therefore, in a retrospective study design, we tested the hypothesis that clinic BP would be significantly reduced following implantation of HF-SCS in patients with chronic pain and hypertension. METHODS: Clinic BP within 3 months before and after surgical implantation of either a LF-SCS or HF-SCS device between 2010 and 2020 were collected from electronic medical records at The University of Kansas Health System (TUKHS). RESULTS: A total of 132 patients had available records of clinic BP (64 ± 13 years of age). Patients with hypertension (n = 32) demonstrated a significantly greater reduction in systolic BP (-8 ± 12 versus 2 ± 9 mmHg, P < 0.001) following implantation compared with normotensive patients (n = 100). Importantly, the change in BP was inversely related to baseline BP independent of age and sex following implantation of HF-SCS (n = 70, R = -0.50, P < 0.001) or LF-SCS (n = 62, R = -0.42, P = 0.001). Higher pain scores before implantation were not associated with reduction in systolic BP (R = 0.10, P = 0.43) or diastolic BP (R = -0.08, P = 0.53) (n = 69) after implantation. CONCLUSION: These findings confirm previous studies showing reduced BP following implantation of LF-SCS in patients with chronic pain and hypertension and provide novel data regarding reduced BP following implantation of newer generation HF-SCS devices.
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Dor Crônica , Hipertensão , Estimulação da Medula Espinal , Humanos , Dor Crônica/terapia , Estudos Retrospectivos , Pressão Arterial , Hipertensão/terapia , Medula Espinal , Resultado do TratamentoRESUMO
OBJECTIVES: High-frequency 10 kHz spinal cord stimulation (10 kHz-SCS) has achieved analgesia superior to traditional SCS in a number of studies. However, there is concern regarding long-term outcomes of 10 kHz-SCS. Prior work has suggested that explant rates are higher with 10 kHz-SCS. Our primary objective was to determine the explant rate of 10 kHz-SCS in a large patient cohort from multiple centers followed for at least 12 months after implant surgery. MATERIALS AND METHODS: We performed a retrospective chart review of all patients who received a 10 kHz-SCS implant before July 1, 2019. We abstracted patient demographics, implant date, primary site of pain, implant indication, explant date, and reason for explant. A total of 744 patients were included in the study analysis. RESULTS: Average age of the overall cohort was 65.53 years and 407 (54.7%) were women. Average follow-up for all patients was 793 days. There were a total of 76 explants (10.2%). The most common reason for explant was loss of efficacy, which accounted for 39 explants (51.3% of total explants, 5.2% of overall cohort). Female sex and radiculopathy as the SCS indication were associated with statistically significant decreased risk of 10 kHz-SCS explant. CONCLUSIONS: We found 10 kHz-SCS explant rates to be similar to prior reported explant rates for traditional SCS devices. Patient-related factors including female sex and radiculopathy as the primary SCS indication may be protective factors against explantation.
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Dor Crônica , Estimulação da Medula Espinal , Idoso , Dor Crônica/terapia , Remoção de Dispositivo , Feminino , Humanos , Masculino , Manejo da Dor , Estudos RetrospectivosRESUMO
The human mind and body respond to stress, a state of perceived threat to homeostasis, by activating the sympathetic nervous system and secreting the catecholamines adrenaline and noradrenaline in the 'fight-or-flight' response. The stress response is generally transient because its accompanying effects (for example, immunosuppression, growth inhibition and enhanced catabolism) can be harmful in the long term. When chronic, the stress response can be associated with disease symptoms such as peptic ulcers or cardiovascular disorders, and epidemiological studies strongly indicate that chronic stress leads to DNA damage. This stress-induced DNA damage may promote ageing, tumorigenesis, neuropsychiatric conditions and miscarriages. However, the mechanisms by which these DNA-damage events occur in response to stress are unknown. The stress hormone adrenaline stimulates ß(2)-adrenoreceptors that are expressed throughout the body, including in germline cells and zygotic embryos. Activated ß(2)-adrenoreceptors promote Gs-protein-dependent activation of protein kinase A (PKA), followed by the recruitment of ß-arrestins, which desensitize G-protein signalling and function as signal transducers in their own right. Here we elucidate a molecular mechanism by which ß-adrenergic catecholamines, acting through both Gs-PKA and ß-arrestin-mediated signalling pathways, trigger DNA damage and suppress p53 levels respectively, thus synergistically leading to the accumulation of DNA damage. In mice and in human cell lines, ß-arrestin-1 (ARRB1), activated via ß(2)-adrenoreceptors, facilitates AKT-mediated activation of MDM2 and also promotes MDM2 binding to, and degradation of, p53, by acting as a molecular scaffold. Catecholamine-induced DNA damage is abrogated in Arrb1-knockout (Arrb1(-/-)) mice, which show preserved p53 levels in both the thymus, an organ that responds prominently to acute or chronic stress, and in the testes, in which paternal stress may affect the offspring's genome. Our results highlight the emerging role of ARRB1 as an E3-ligase adaptor in the nucleus, and reveal how DNA damage may accumulate in response to chronic stress.
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Arrestinas/metabolismo , Dano ao DNA , Receptores Adrenérgicos beta 2/metabolismo , Estresse Fisiológico/fisiologia , Animais , Arrestinas/deficiência , Arrestinas/genética , Catecolaminas/farmacologia , Linhagem Celular , Núcleo Celular/enzimologia , Núcleo Celular/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Fibroblastos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Testículo/metabolismo , Timo/metabolismo , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/metabolismo , beta-Arrestina 1 , beta-ArrestinasRESUMO
Background: Chronic abdominal pain (CAP) is a common and challenging to treat condition with a global prevalence of up to 25%. Despite extensive evaluation, approximately 40% of patients with CAP have an unknown diagnosis. Medications may be ineffective, and surgery is rarely indicated. Interventional treatment including sympathetic blocks, sympathetic neurolysis, and transversus abdominal plane (TAP) blocks may be an option, but their efficacy can wane over time. Neuromodulation has emerged as an option for these patients, as there is evidence of success with dorsal column spinal cord and dorsal root ganglion (DRG) stimulation. Peripheral nerve stimulation (PNS) may be an alternative option, particularly in higher risk patients or in patients for whom neuraxial access may be unsafe or too technically challenging. Thoracoabdominal nerve peripheral nerve stimulation via a TAP approach may be more specifically targeted in comparison to dorsal column or DRG stimulation. In this short report, we detail a technique that the authors have successfully used for thoracoabdominal nerve PNS via a TAP approach for management of CAP. Methods: This article describes a novel medial to lateral ultrasound guided thoracoabdominal nerve PNS via a TAP approach technique for lead placement and implantation. Results: A medial to lateral ultrasound guided TAP approach as described to successfully implant percutaneous thoracoabdominal nerve PNS leads for management of CAP. Conclusion: The thoracoabdominal nerve PNS via a TAP approach lead placement technique noted in this report has been used as a means for management of CAP utilizing peripheral neuromodulation. Here, we present a short report detailing a potential technique for PNS utilization for management of CAP. Further studies are needed to validate the safety and efficacy of this therapy modality, although the authors have found it to be a viable management option for patients with medically refractory neuropathic CAP.
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BACKGROUND: Lumbar medial branch nerve radiofrequency ablation (LRFA) is an interventional procedure used to treat chronic lumbar facet joint pain. Because the medial branch nerves also innervate the multifidus muscle, it has been proposed that LRFA may pose a risk of multifidus atrophy and/or dysfunction. However, the quality and level of evidence to answer this clinical question have not been established. Therefore, this review aimed to systematically appraise the literature to discern whether the prevailing evidence substantiates the hypothesis in question. METHODS: A systematic review compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed to evaluate the quality and level of evidence of studies reporting functional and/or structural changes in the multifidus muscle following LRFA. RESULTS: Only five cohort studies met inclusion criteria. Two studies assessed changes in multifidus function following LRFA with confirmed denervation at electromyography and significant reduction in multifidus shear modulus with ultrasound shear wave elastography. Of the four studies that evaluated changes in multifidus structure with magnetic resonance imaging following LRFA, two demonstrated a decrease in cross-sectional area or an increase in fat infiltration, one demonstrated no change, and one revealed an apparent increase. Given the destructive nature attributed to LRFA, some degree of multifidus atrophy and/or dysfunction may be plausible, albeit with a very low certainty that relies on a restricted body of literature of modest quality and with a presence of high bias. CONCLUSION: There is a paucity of studies discussing the potential association between LRFA and multifidus atrophy and/or dysfunction. In light of the shortage of high-quality studies and the absence of standardized protocols to assess both changes in the structure and function of the multifidus subsequent to LRFA, there is a pressing need for more prospective studies with a high methodological rigor to comprehensively address and answer this enduring debate in clinical practice.
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Introduction: Research suggests that sacroiliac joint (SIJ) dysfunction is responsible for 15% to 30% of reported low back pain cases. Recently, there has been an increasing interest in SIJ fusion using minimally invasive surgery (MIS) due to safety. Initially, devices designed for MIS were intended for lateral approaches. A minimally invasive sacroiliac fusion implant for use with a posterior approach has been developed and is regulated for clinical use under the regulatory framework required for human cells, tissues, or cellular or tissue-based products (HCT/Ps). Methods: A multi-center, prospective, single-arm study was launched after initial studies provided preliminary data to support safety, efficacy, and durability of this minimally invasive sacroiliac posterior fusion LinQ allograft implant (NCT04423120). Preliminary results were reported previously. Final results for the full participant cohort are presented here. Results: One-hundred and fifty-nine (159) participants were enrolled across 16 investigational sites in the US between January 2020 and March 2022. One-hundred and twenty-two (122) participants were implanted. At the 1-month follow-up, 82 participants satisfied all criteria for the composite responder endpoint, representing 73.2% of the study cohort. These results stayed consistent across the remaining study timepoints with 66.0%, 74.4%, and 73.5% of participants classified as responders at the 3-, 6- and 12-month follow-up visits, respectively. VAS scores were significantly reduced (p < 0.0001) and ODI scores were significantly improved (p < 0.0001). All domains of the PROMIS-29 were also significantly improved (all p's <0.0001). Only one procedure-related serious AE was reported in the study. Conclusion: These results suggest that the posterior approach LinQ Implant System is a safe and effective treatment for sacroiliac joint dysfunction at 12 months, with results that are favorable compared to outcomes reported for an FDA-cleared lateral approach.
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Chronic pain constitutes a significant disease burden globally and accounts for a substantial portion of healthcare spending. The COVID-19 pandemic contributed to an increase in this burden as patients presented with musculoskeletal or neuropathic pain after contracting COVID-19 or had their chronic pain symptoms exacerbated by the virus. This extensive literature review analyzes the epidemiology of pain pre-pandemic, the costs associated with the COVID-19 pandemic, the impact of the virus on the body, mechanisms of pain, management of chronic pain post-pandemic, and potential treatment options available for people living with chronic pain who have had or are currently infected with COVID-19.
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Spinal cord stimulation (SCS) is a well-established treatment for patients with chronic pain. With increasing healthcare costs, it is important to determine the benefits of SCS in healthcare utilization (HCU). This retrospective, single-center observational study involved 160 subjects who underwent implantation of a high-frequency (10 kHz) SCS device. We focused on assessing trends in HCU by measuring opioid consumption in morphine milligram equivalents (MME), as well as monitoring emergency department (ED) and office visits for interventional pain procedures during the 12-month period preceding and following the SCS implant. Our results revealed a statistically significant reduction in HCU in all domains assessed. The mean MME was 51.05 and 26.52 pre- and post-implant, respectively. There was a 24.53 MME overall decrease and a mean of 78.2% statistically significant dose reduction (p < 0.0001). Of these, 91.5% reached a minimally clinically important difference (MCID) in opioid reduction. Similarly, we found a statistically significant (p < 0.01) decrease in ED visits, with a mean of 0.12 pre- and 0.03 post-implant, and a decrease in office visits for interventional pain procedures from a 1.39 pre- to 0.28 post-10 kHz SCS implant, representing a 1.11 statistically significant (p < 0.0001) mean reduction. Our study reports the largest cohort of real-world data published to date analyzing HCU trends with 10 kHz SCS for multiple pain etiologies. Furthermore, this is the first and only study evaluating HCU trends with 10 kHz SCS by assessing opioid use, ED visits, and outpatient visits for interventional pain procedures collectively. Preceding studies have individually investigated these outcomes, consistently yielding positive results comparable to our findings.
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INTRODUCTION: Drawbacks of fixed-output spinal cord stimulation (SCS) screening trials may lead to compromised trial outcomes and poor predictability of long-term success. Evoked compound action potential (ECAP) dose-controlled closed-loop (CL) SCS allows objective confirmation of therapeutic neural activation and pulse-to-pulse stimulation adjustment. We report on the immediate patient-reported and neurophysiologic treatment response post-physiologic CL-SCS and feasibility of early SCS trial responder prediction. METHODS: Patient-reported pain relief, functional improvement, and willingness to proceed to permanent implant were compared between the day of the trial procedure (Day 0) and end of trial (EOT) for 132 participants in the ECAP Study undergoing a trial stimulation period. ECAP-based neurophysiologic measurements from Day 0 and EOT were compared between responder groups. RESULTS: A high positive predictive value (PPV) was achieved with 98.4% (60/61) of patients successful on the Day 0 evaluation also responding at EOT. The false-positive rate (FPR) was 5.6% (1/18). ECAP-based neurophysiologic measures were not different between patients who passed all Day 0 success criteria ("Day 0 successes") and those who did not ("needed longer to evaluate the therapy"). However, at EOT, responders had higher therapeutic usage and dose levels compared to non-responders. CONCLUSIONS: The high PPV and low FPR of the Day 0 evaluation provide confidence in predicting trial outcomes as early as the day of the procedure. Day 0 trials may be beneficial for reducing patient burden and complication rates associated with extended trials. ECAP dose-controlled CL-SCS therapy may provide objective data and rapid-onset pain relief to improve prognostic ability of SCS trials in predicting outcomes. TRIAL REGISTRATION: The ECAP Study is registered with ClinicalTrials.gov (NCT04319887).
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Clinical management of sacroiliac disease has proven challenging from both diagnostic and therapeutic perspectives. Although it is widely regarded as a common source of low back pain, little consensus exists on the appropriate clinical management of sacroiliac joint pain and dysfunction. Understanding the biomechanics, innervation, and function of this complex load bearing joint is critical to formulating appropriate treatment algorithms for SI joint disorders. ASPN has developed this comprehensive practice guideline to serve as a foundational reference on the appropriate management of SI joint disorders utilizing the best available evidence and serve as a foundational guide for the treatment of adult patients in the United States and globally.
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Introduction: Painful diabetic neuropathy (PDN) is a leading cause of pain and disability globally with a lack of consensus on the appropriate treatment of those suffering from this condition. Recent advancements in both pharmacotherapy and interventional approaches have broadened the treatment options for PDN. There exists a need for a comprehensive guideline for the safe and effective treatment of patients suffering from PDN. Objective: The SWEET Guideline was developed to provide clinicians with the most comprehensive guideline for the safe and appropriate treatment of patients suffering from PDN. Methods: The American Society of Pain and Neuroscience (ASPN) identified an educational need for a comprehensive clinical guideline to provide evidence-based recommendations for PDN. A multidisciplinary group of international experts developed the SWEET guideline. The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Meeting Abstracts, and Scopus to identify and compile the evidence for diabetic neuropathy pain treatments (per section as listed in the manuscript) for the treatment of pain. Manuscripts from 2000-present were included in the search process. Results: After a comprehensive review and analysis of the available evidence, the ASPN SWEET guideline was able to rate the literature and provide therapy grades for most available treatments for PDN utilizing the United States Preventive Services Task Force criteria. Conclusion: The ASPN SWEET Guideline represents the most comprehensive review of the available treatments for PDN and their appropriate and safe utilization.
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Ubiquitously expressed seven-transmembrane receptors (7TMRs) classically signal through heterotrimeric G proteins and are commonly referred to as G protein-coupled receptors. It is now recognized that 7TMRs also signal through beta-arrestins, which act as versatile adapters controlling receptor signaling, desensitization, and trafficking. Most endogenous receptors appear to signal in a balanced fashion using both beta-arrestin and G protein-mediated pathways. Some 7TMRs are thought to be nonsignaling "decoys" because of their inability to activate typical G protein signaling pathways; it has been proposed that these receptors act to scavenge ligands or function as coreceptors. Here we demonstrate that ligand binding to the decoy receptor CXCR7 does not result in activation of signaling pathways typical of G proteins but does activate MAP kinases through beta-arrestins in transiently transfected cells. Furthermore, we observe that vascular smooth muscle cells that endogenously express CXCR7 migrate to its ligand interferon-inducible T-cell alpha chemoattractant (ITAC), an effect that is significantly attenuated by treatment with either a CXCR7 antagonist or beta-arrestin depletion by siRNA. This example of an endogenous "beta-arrestin-biased" 7TMR that signals through beta-arrestin in the absence of G protein activation demonstrates that some 7TMRs encoded in the genome have evolved to signal through beta-arrestin exclusively and suggests that other receptors that are currently thought to be orphans or decoys may also signal through such nonclassical pathways.
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Arrestinas/fisiologia , Receptores CXCR/fisiologia , Linfócitos T/fisiologia , Animais , Linhagem Celular , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/fisiologia , Humanos , Camundongos , Músculo Liso Vascular/fisiologia , Fosforilação , RNA Mensageiro/genética , Ratos , Receptores CXCR/genética , Receptores de Quimiocinas/genética , Transdução de Sinais/fisiologia , Linfócitos T/citologia , beta-ArrestinasRESUMO
BACKGROUND: Chronic pelvic pain (CPP) is a pervasive, difficult to treat condition affecting up to 26% of the global female and 8.2% of the global male population. Considered a form of chronic regional pain syndrome (CRPS), it is medically complex and often refractory to multimodal management. Neuromodulation has become increasingly popular in treatment of chronic neuropathic pain conditions, including CPP and CRPS. Dorsal column spinal cord stimulation and dorsal root ganglion stimulation have had some success for managing CPP meanwhile peripheral nerve stimulators (PNS) have been suggested as another viable option. However, few studies in the literature have reported successful use of PNS in treatment of CPP. Here, we detail a possible technique for pudendal PNS lead placement for management of CPP. METHOD: This article describes a novel cephalad to caudad fluoroscopic guided technique for pudendal nerve PNS lead placement and implantation. RESULTS: A cephalad to caudal-medial fluoroscopic guided approach as described within to successfully implant a percutaneous pudendal nerve PNS for management of CPP. CONCLUSIONS: The pudendal nerve PNS lead placement technique noted within can be used to avoid many of the important neurovascular structures near the pelvic outlet. Further studies are needed to validate the safety and efficacy of this therapy modality but it may be a viable management option for patients with medically refractory CPP.
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Dor Crônica , Síndromes da Dor Regional Complexa , Nervo Pudendo , Estimulação da Medula Espinal , Estimulação Elétrica Nervosa Transcutânea , Humanos , Masculino , Feminino , Dor Crônica/diagnóstico , Dor Crônica/terapia , Estimulação da Medula Espinal/métodos , Dor Pélvica/terapiaRESUMO
Objective: Baroreceptors play a significant role in nociceptive pain. However, the extent to which baroreceptors modulate nociception in patients with chronic pain is unclear. We tested the hypothesis that cardiopulmonary baroreceptor unloading via LBNP would significantly increase pressure pain threshold and habituation to heat pain among patients with chronic back pain. Methods: Mechanical pressure pain threshold at the upper trapezius (hand-held algometer) and habituation to heat pain at the forearm were performed during sitting and supine position, and during baroreceptor unloading via lower body negative pressure (LBNP) of -10 mmHg in 12 patients with chronic back pain (54 ± 11 years of age). To determine whether pain reduction is normal during LBNP, studies were repeated in 7 young, healthy participants (23 ± 7). Results: Mechanical pressure pain threshold (P < 0.01) and habituation to heat pain (P = 0.04) were significantly reduced during supine compared with sitting. Conversely, baroreceptor unloading via LBNP significantly increased pressure pain threshold (P = 0.03) and heat pain habituation (P < 0.01) compared with supine. In young healthy controls, pressure pain threshold was similarly affected when comparing sitting and supine (P = 0.01) and during LBNP (P < 0.01), whereas habituation to heat pain was unaltered when comparing sitting and supine (P = 0.93) and during LBNP (P = 0.90). Total peripheral resistance was increased during LBNP (P = 0.01) but not among young, healthy controls (P = 0.71). Conclusions: The findings demonstrate cardiopulmonary baroreceptor modulation of nociceptive pain in patients with chronic pain. Interestingly, habituation to heat pain appears more readily modified by cardiopulmonary baroreceptors in patients with chronic back pain compared with young, healthy individuals.
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Neuromodulation, specifically spinal cord stimulation (SCS), has become a staple of chronic pain management for various conditions including failed back syndrome, chronic regional pain syndrome, refractory radiculopathy, and chronic post operative pain. Since its conceptualization, it has undergone several advances to increase safety and convenience for patients and implanting physicians. Current research and efforts are aimed towards novel programming modalities and modifications of existing hardware. Here we review the recent advances and future directions in spinal cord stimulation including a brief review of the history of SCS, SCS waveforms, new materials for SCS electrodes (including artificial skins, new materials, and injectable electrodes), closed loop systems, and neurorestorative devices.
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The objective of this peripheral nerve stimulation consensus guideline is to add to the current family of consensus practice guidelines and incorporate a systematic review process. The published literature was searched from relevant electronic databases, including PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science from database inception to March 29, 2021. Inclusion criteria encompassed studies that described peripheral nerve stimulation in patients in terms of clinical outcomes for various pain conditions, physiological mechanism of action, surgical technique, technique of placement, and adverse events. Twenty randomized controlled trials and 33 prospective observational studies were included in the systematic review process. There is Level I evidence supporting the efficacy of PNS for treatment of chronic migraine headaches via occipital nerve stimulation; chronic hemiplegic shoulder pain via stimulation of nerves innervating the trapezius, supraspinatus, and deltoid muscles; failed back surgery syndrome via subcutaneous peripheral field stimulation; and lower extremity neuropathic and lower extremity post-amputation pain. Evidence from current Level I studies combined with newer technologies facilitating less invasive and easier electrode placement make peripheral nerve stimulation an attractive alternative for managing patients with complex pain disorders. Peripheral nerve stimulation should be used judiciously as an adjunct for chronic and acute postoperative pain following adequate patient screening and positive diagnostic nerve block or stimulation trial.
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Chronic low back pain is a worldwide leading cause of pain and disability. Degenerative disc disease has been the presumptive etiology in the majority of cases of chronic low back pain (CLBP). More recent study and treatments have discovered that the vertebral endplates play a large role in CLBP in a term defined as vertebrogenic back pain. As the vertebral endplates are highly innervated via the basivertebral nerve (BVN), this has resulted in a reliable target in treating patients suffering from vertebrogenic low back pain (VLBP). The application of BVN ablation for patients suffering from VLBP is still in its early stages of adoption and integration into spine care pathways. BVN ablation is grounded in a solid foundation of both pre-clinical and clinical evidence. With the emergence of this therapeutic option, the American Society of Pain and Neuroscience (ASPN) identified the need for formal evidence-based guidelines for the proper identification and selection of patients for BVN ablation in patients with VLBP. ASPN formed a multidisciplinary work group tasked to examine the available literature and form best practice guidelines on this subject. Based on the United States Preventative Task Force (USPSTF) criteria for grading evidence, gives BVN ablation Level A grade evidence with high certainty that the net benefit is substantial in appropriately selected individuals.
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Introduction: Painful lumbar spinal disorders represent a leading cause of disability in the US and worldwide. Interventional treatments for lumbar disorders are an effective treatment for the pain and disability from low back pain. Although many established and emerging interventional procedures are currently available, there exists a need for a defined guideline for their appropriateness, effectiveness, and safety. Objective: The ASPN Back Guideline was developed to provide clinicians the most comprehensive review of interventional treatments for lower back disorders. Clinicians should utilize the ASPN Back Guideline to evaluate the quality of the literature, safety, and efficacy of interventional treatments for lower back disorders. Methods: The American Society of Pain and Neuroscience (ASPN) identified an educational need for a comprehensive clinical guideline to provide evidence-based recommendations. Experts from the fields of Anesthesiology, Physiatry, Neurology, Neurosurgery, Radiology, and Pain Psychology developed the ASPN Back Guideline. The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Scopus, and meeting abstracts to identify and compile the evidence (per section) for back-related pain. Search words were selected based upon the section represented. Identified peer-reviewed literature was critiqued using United States Preventive Services Task Force (USPSTF) criteria and consensus points are presented. Results: After a comprehensive review and analysis of the available evidence, the ASPN Back Guideline group was able to rate the literature and provide therapy grades to each of the most commonly available interventional treatments for low back pain. Conclusion: The ASPN Back Guideline represents the first comprehensive analysis and grading of the existing and emerging interventional treatments available for low back pain. This will be a living document which will be periodically updated to the current standard of care based on the available evidence within peer-reviewed literature.
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Seven transmembrane receptors (7TMRs), commonly referred to as G protein-coupled receptors, form a large part of the "druggable" genome. 7TMRs can signal through parallel pathways simultaneously, such as through heterotrimeric G proteins from different families, or, as more recently appreciated, through the multifunctional adapters, ß-arrestins. Biased agonists, which signal with different efficacies to a receptor's multiple downstream pathways, are useful tools for deconvoluting this signaling complexity. These compounds may also be of therapeutic use because they have distinct functional and therapeutic profiles from "balanced agonists." Although some methods have been proposed to identify biased ligands, no comparison of these methods applied to the same set of data has been performed. Therefore, at this time, there are no generally accepted methods to quantify the relative bias of different ligands, making studies of biased signaling difficult. Here, we use complementary computational approaches for the quantification of ligand bias and demonstrate their application to two well known drug targets, the ß2 adrenergic and angiotensin II type 1A receptors. The strategy outlined here allows a quantification of ligand bias and the identification of weakly biased compounds. This general method should aid in deciphering complex signaling pathways and may be useful for the development of novel biased therapeutic ligands as drugs.