Medical Cannabis: A Review from the American Society of Pain and Neuroscience.

Cannabinoids have recently gained a renewed interest due to their potential applicability to various medical conditions, specifically the management of chronic pain conditions. Unlike many other medications, medical cannabis is not associated with serious adverse events, and no overdose deaths have been reported. However, both safety and efficacy data for medical cannabis treatment of chronic, nonmalignant pain conditions are lacking. Therefore, representatives from the American Society of Pain and Neuroscience summarize the evidence, according to level and grade, for medical cannabis treatment of several different pain conditions. Treatment of cancer-related pain has prospective evidentiary support for the use of medical cannabis. Although 3 large and well-designed randomized controlled trials investigated cannabis treatment of cancer-related pain, the evidence yielded only a grade D recommendation. Neuropathic pain has been investigated in prospective studies, but a lack of high-quality evidence renders cannabis treatment for this indication a grade C recommendation. Both safety and efficacy data are lacking for use of medical cannabis to treat chronic nonmalignant pain conditions.

A Prospective, Observational, Open-Label, Non-Randomized, Multicenter Study Measuring Functional Outcomes in a Novel Interspinous Fusion Device in Subjects with Low Back Pain: REFINE Study.

INTRODUCTION: Lumbar degenerative disease and the accompanying pain and dysfunction affect a significant number of patients in the USA and around the world. As surgery and innovation are moving towards minimally invasive treatments, this study looks to explore interspinous fixation as a standalone posterior approach to treat lumbar degenerative disc disease in the presence of neurogenic claudication and spinal stenosis. METHODS: This study was approved by an institutional review board (IRB) and is actively enrolling in a single-arm, multicenter, prospective, open-label fashion. Patients are followed with reporting at 3 months, and 12 months for primary endpoint analysis of efficacy and safety based on improved composite endpoints relative to baseline, with success defined as greater than 20 mm back pain reduction in Visual Analog Scale 100 mm (VAS) while standing or walking, greater than 20 mm leg pain reduction in VAS while standing or walking, Zurich Claudication Questionnaire (ZCQ) improvement of 0.5 or greater in two or three domains, Oswestry Disability Index (ODI) improvement of a least 10 points and no reoperations or revisions at the index level(s). Secondary endpoints included a multidimensional assessment in the Patient-Reported Outcomes Measurement Information System (PROMIS) 29 v2.1 and Patient Global Impression of Change (PGIC). RESULTS: In this interim 3-month analysis, 82% of patients reported they were improved from the procedure, while 65% of patients demonstrated clinical meaningful improvement in their pain and function, as defined by the VAS, ODI, and ZCQ. There was only one adverse event and no complications were identified at last clinic research follow-up visit. CONCLUSIONS: This interim analysis of the first 20% of the enrolled patients out to 3 months was to determine safety of the procedure and report on adverse events, acknowledging the heterogeneity of surgical specialty. Further follow-up and greater numbers are needed as the study is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05504499.

A post-market, randomized, controlled, prospective study evaluating intrathecal pain medication versus conventional medical management in the non-cancer, refractory, chronic pain population (PROSPER).

INTRODUCTION: Intrathecal therapy has been limited by non-randomized prospective studies, particularly for those suffering from non-cancer. Further, no prospective, randomized studies investigating the efficacy, safety, and utilization of intrathecal polyanalgesic consensus guidelines exist. METHODS: After IRB approval, patients were enrolled in a 1:1 fashion for intrathecal drug delivery (IDD) or conventional management (CMM), employing standard of care, excluding intrathecal drug delivery, based on the principal investigator's discretion. They were followed 3, 6, 9, and 12 months. Assessments included PROMIS 29, NPRS, and PriceMonkey. RESULTS: Seventy-nine patients were screened, 54 patients were enrolled: 26 to IDD and 28 to CMM. At 3 months, there was no measurable difference in pain improvement in either subgroups within the CMM for chronic pain-related syndromes (CPRS) or failed back and related spine disorders (FBRS). For the IDD, early and maintained benefit from the baseline was statistically achieved. Cost analysis of pump to CMM breakeven was 4.5 months. There were no adverse events related to compounded intrathecal medications. CONCLUSION: This is the first randomized prospective, multicenter study investigating the safety, cost, and efficacy of off-label medications for intrathecal therapy, as compared to conventional management, and suggests early detection of improvement, cost savings, safety of intrathecal compounded medication use, and safety and efficacy of employing the PACC guidance.

Best Practices for Minimally Invasive Lumbar Spinal Stenosis Treatment 2.0 (MIST): Consensus Guidance from the American Society of Pain and Neuroscience (ASPN).

Introduction: Lumbar spinal stenosis (LSS) is a common spinal disease of aging with a growing patient population, paralleling population growth. Minimally invasive treatments are evolving, and the use of these techniques needs guidance to provide the optimal patient safety and efficacy outcomes. Methods: The American Society of Pain and Neuroscience (ASPN) identified an educational need for guidance on the prudent use of the innovative minimally invasive surgical therapies for the treatment of symptomatic LSS. The executive board nominated experts spanning anesthesiology, physiatry, orthopedic surgery, and neurosurgery based on expertise, publications, research, diversity and field of practice. Evidence was reviewed, graded using the United States Preventive Services Task Force (USPSTF) criteria for evidence and recommendation strength and grade, and expert opinion was added to make consensus points for best practice. Results: 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 LSS-related pain. Search words were selected based upon the section represented. Identified peer-reviewed literature was critiqued using USPSTF criteria and consensus points are presented. Discussion: The algorithm for patient selection in the management of symptomatic spinal stenosis is evolving. Careful consideration of patient selection and anatomic architecture variance is critical for improved outcomes and patient safety. Conclusion: ASPN created a guidance for best practice for minimally invasive surgical treatment of symptomatic spinal stenosis.

Diagnosis, Treatment, and Management of Painful Scar: A Narrative Review.

Painful scars can develop after surgery or trauma, with symptoms ranging from a minor itch to intractable allodynia. The problem of the painful scar may involve both intraneural and extraneural structures, requiring a systematic approach to diagnosis and treatment of this neuropathic pain condition that can impact quality of life and function profoundly. In this review, we outline the algorithm for the diagnosis, management, medical and surgical treatment of painful scars.

A Systematic Literature Review of Spine Neurostimulation Therapies for the Treatment of Pain.

OBJECTIVE: To conduct a systematic literature review of spinal cord stimulation (SCS) for pain. DESIGN: Grade the evidence for SCS. METHODS: An international, interdisciplinary work group conducted literature searches, reviewed abstracts, and selected studies for grading. Inclusion/exclusion criteria included randomized controlled trials (RCTs) of patients with intractable pain of greater than one year's duration. Full studies were graded by two independent reviewers. Excluded studies were retrospective, had small numbers of subjects, 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: SCS has Level 1 evidence (strong) for axial back/lumbar radiculopathy or neuralgia (five high-quality RCTs) and complex regional pain syndrome (one high-quality RCT). CONCLUSIONS: High-level evidence supports SCS for treating chronic pain and complex regional pain syndrome. For patients with failed back surgery syndrome, SCS was more effective than reoperation or medical management. New stimulation waveforms and frequencies may provide a greater likelihood of pain relief compared with conventional SCS for patients with axial back pain, with or without radicular pain.

Long-term safety and efficacy of closed-loop spinal cord stimulation to treat chronic back and leg pain (Evoke): a double-blind, randomised, controlled trial.

BACKGROUND: Spinal cord stimulation has been an established treatment for chronic back and leg pain for more than 50 years; however, outcomes are variable and unpredictable, and objective evidence of the mechanism of action is needed. A novel spinal cord stimulation system provides the first in vivo, real-time, continuous objective measure of spinal cord activation in response to therapy via recorded evoked compound action potentials (ECAPs) in patients during daily use. These ECAPs are also used to optimise programming and deliver closed-loop spinal cord stimulation by adjusting the stimulation current to maintain activation within patients' therapeutic window. We aimed to examine pain relief and the extent of spinal cord activation with ECAP-controlled closed-loop versus fixed-output, open-loop spinal cord stimulation for the treatment of chronic back and leg pain. METHODS: This multicentre, double-blind, parallel-arm, randomised controlled trial was done at 13 specialist clinics, academic centres, and hospitals in the USA. Patients with chronic, intractable pain of the back and legs (Visual Analog Scale [VAS] pain score ≥60 mm; Oswestry Disability Index [ODI] score 41-80) who were refractory to conservative therapy, on stable pain medications, had no previous experience with spinal cord stimulation, and were appropriate candidates for a spinal cord stimulation trial were screened. Eligible patients were randomly assigned (1:1) to receive ECAP-controlled closed-loop spinal cord stimulation (investigational group) or fixed-output, open-loop spinal cord stimulation (control group). The randomisation sequence was computer generated with permuted blocks of size 4 and 6 and stratified by site. Patients, investigators, and site staff were masked to the treatment assignment. The primary outcome was the proportion of patients with a reduction of 50% or more in overall back and leg pain with no increase in pain medications. Non-inferiority (δ=10%) followed by superiority were tested in the intention-to-treat population at 3 months (primary analysis) and 12 months (additional prespecified analysis) after the permanent implant. This study is registered with ClinicalTrials.gov, NCT02924129, and is ongoing. FINDINGS: Between Feb 21, 2017, and Feb 20, 2018, 134 patients were enrolled and randomly assigned (67 to each treatment group). The intention-to-treat analysis comprised 125 patients at 3 months (62 in the closed-loop group and 63 in the open-loop group) and 118 patients at 12 months (59 in the closed-loop group and 59 in the open-loop group). The primary outcome was achieved in a greater proportion of patients in the closed-loop group than in the open-loop group at 3 months (51 [82·3%] of 62 patients vs 38 [60·3%] of 63 patients; difference 21·9%, 95% CI 6·6-37·3; p=0·0052) and at 12 months (49 [83·1%] of 59 patients vs 36 [61·0%] of 59 patients; difference 22·0%, 6·3-37·7; p=0·0060). We observed no differences in safety profiles between the two groups. The most frequently reported study-related adverse events in both groups were lead migration (nine [7%] patients), implantable pulse generator pocket pain (five [4%]), and muscle spasm or cramp (three [2%]). INTERPRETATION: ECAP-controlled closed-loop stimulation provided significantly greater and more clinically meaningful pain relief up to 12 months than open-loop spinal cord stimulation. Greater spinal cord activation seen in the closed-loop group suggests a mechanistic explanation for the superior results, which aligns with the putative mechanism of action for spinal cord stimulation and warrants further investigation. FUNDING: Saluda Medical.

Intrathecal Therapy for Chronic Pain: A Review of Morphine and Ziconotide as Firstline Options.

OBJECTIVES: To evaluate the evidence for morphine and ziconotide as firstline intrathecal (IT) analgesia agents for patients with chronic pain. METHODS: Medline was searched (through July 2017) for "ziconotide" or "morphine" AND "intrathecal" AND "chronic pain," with results limited to studies in human populations. RESULTS: The literature supports the use of morphine (based primarily on noncontrolled, prospective, and retrospective studies) and ziconotide (based on randomized controlled trials and prospective observational studies) as first-choice IT therapies. The 2016 Polyanalgesic Consensus Conference (PACC) guidelines recommended both morphine and ziconotide as firstline IT monotherapy for localized and diffuse chronic pain of cancer-related and non-cancer-related etiologies; however, one consensus point emphasized ziconotide use, unless contraindicated, as firstline IT therapy in patients with chronic non-cancer-related pain. Initial IT therapy choice should take into consideration individual patient characteristics (e.g., pain location, response to previous therapies, comorbid medical conditions, psychiatric history). Trialing is recommended to assess medication efficacy and tolerability. For both morphine and ziconotide, the PACC guidelines recommend conservative initial dosing strategies. Due to its narrow therapeutic window, ziconotide requires careful dose titration. Ziconotide is contraindicated in patients with a history of psychosis. IT morphine administration may be associated with serious side effects (e.g., respiratory depression, catheter tip granuloma), require dose increases, and cause dependence over time. CONCLUSION: Based on the available evidence, morphine and ziconotide are recommended as firstline IT monotherapy for cancer-related and non-cancer-related pain. The choice of first-in-pump therapy should take into consideration patient characteristics and the advantages and disadvantages of each medication.

The MIST Guidelines: The Lumbar Spinal Stenosis Consensus Group Guidelines for Minimally Invasive Spine Treatment.

BACKGROUND: Lumbar spinal stenosis (LSS) can lead to compression of neural elements and manifest as low back and leg pain. LSS has traditionally been treated with a variety of conservative (pain medications, physical therapy, epidural spinal injections) and invasive (surgical decompression) options. Recently, several minimally invasive procedures have expanded the treatment options. METHODS: The Lumbar Spinal Stenosis Consensus Group convened to evaluate the peer-reviewed literature as the basis for making minimally invasive spine treatment (MIST) recommendations. Eleven consensus points were clearly defined with evidence strength, recommendation grade, and consensus level using U.S. Preventive Services Task Force criteria. The Consensus Group also created a treatment algorithm. Literature searches yielded 9 studies (2 randomized controlled trials [RCTs]; 7 observational studies, 4 prospective and 3 retrospective) of minimally invasive spine treatments, and 1 RCT for spacers. RESULTS: The LSS treatment choice is dependent on the degree of stenosis; spinal or anatomic level; architecture of the stenosis; severity of the symptoms; failed, past, less invasive treatments; previous fusions or other open surgical approaches; and patient comorbidities. There is Level I evidence for percutaneous image-guided lumbar decompression as superior to lumbar epidural steroid injection, and 1 RCT supported spacer use in a noninferiority study comparing 2 spacer products currently available. CONCLUSIONS: MISTs should be used in a judicious and algorithmic fashion to treat LSS, based on the evidence of efficacy and safety in the peer-reviewed literature. The MIST Consensus Group recommend that these procedures be used in a multimodal fashion as part of an evidence-based decision algorithm.

Multicenter Retrospective Study of Neurostimulation With Exit of Therapy by Explant.

INTRODUCTION: Spinal cord stimulation (SCS) devices are cost effective and improve function as well as quality of life. Despite the demonstrated benefits of SCS, some patients have the device explanted. We are interested in exploring the patient characteristics of those explanted. METHODS: This is a retrospective chart review of neurostimulation patients who underwent explantation at 18 centers across the United States within the previous five years. RESULTS: Data from 352 patients were collected and compiled. Failed Back Surgery syndrome was the most common diagnosis (38.9%; n = 136/350) and over half of the patients reported numerical rating scale (NRS) scores ≥8 prior to implant (64.3%; n = 207/322). All patients reported changes in NRS scores across time, with an initial decrease after implant followed by a pre-explant increase (F (2, 961) = 121.7, p < 0.001). The most common reason for device explant was lack or loss of efficacy (43.9%; 152/346) followed by complications (20.2%; 70/346). Eighteen percent (18%; 62/343) of patients were explanted by a different physician than the implanting one. Rechargeable devices were explanted at a median of 15 months, whereas primary cell device explants occurred at a median of 36 months (CI 01.434, 2.373; median endpoint time ratio = 2.40). DISCUSSION: Loss or lack of efficacy and complications with therapy represent the most frequent reasons for neurostimulation explantation. Of the devices that were explanted, therapy was terminated earlier when devices were rechargeable, when complications occurred, or when pain relief was not achieved or maintained. Furthermore, in nearly 20% of the cases, a different provider than the implanting physician performed device removal. CONCLUSIONS: SCS is largely a safe and efficacious strategy for treating select chronic refractory pain syndromes. Further prospective data and innovation are needed to improve patient selection, maintain SCS therapeutic efficacy and reduce the reasons that lead to device explant.

Evaluation of Abbott's BurstDR stimulation device for the treatment of chronic pain.

INTRODUCTION: Burst stimulation, as described by DeRidder, is a novel waveform made up of closely spaced, high-frequency electrical impulses delivered in packets, which are followed by a quiescent period or interburst interval. Electrically generated burst waveforms were initially designed to treat neural pathology in the auditory cortex and were later applied to the spinal cord through spinal cord stimulation (SCS) devices to treat chronic pain states. When Burst stimulation is applied to the spinal cord, the impulses travel to the thalamus and then diverge, targeting both the somatosensory cortex and the limbic system where they treat both the sensory, affective and attentional components of neuropathic pain. Areas covered: Literature examining clinical and basic research findings with the application of Burst stimulation to pathologically active central neural tissue was found using bibliographic databases including PubMed, Medline, Cochrane, Embase and Google Scholar. Expert commentary: Burst stimulation offers a salvage strategy for failed tonic spinal cord stimulation (tSCS), thus improving both quality of life and cost-effectiveness of SCS by reducing explant rates. The goal of this therapy is to use more than one waveform in the same device so that lost efficacy from tSCS can be salvaged.

The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines.

INTRODUCTION: Pain treatment is best performed when a patient-centric, safety-based philosophy is used to determine an algorithmic process to guide care. Since 2007, the International Neuromodulation Society has organized a group of experts to evaluate evidence and create a Polyanalgesic Consensus Conference (PACC) to guide practice. METHODS: The current PACC update was designed to address the deficiencies and innovations emerging since the previous PACC publication of 2012. An extensive literature search identified publications between January 15, 2007 and November 22, 2015 and authors contributed additional relevant sources. After reviewing the literature, the panel convened to determine evidence levels and degrees of recommendations for intrathecal therapy. This meeting served as the basis for consensus development, which was ranked as strong, moderate or weak. Algorithms were developed for intrathecal medication choices to treat nociceptive and neuropathic pain for patients with cancer, terminal illness, and noncancer pain, with either localized or diffuse pain. RESULTS: The PACC has developed an algorithmic process for several aspects of intrathecal drug delivery to promote safe and efficacious evidence-based care. Consensus opinion, based on expertise, was used to fill gaps in evidence. Thirty-one consensus points emerged from the panel considerations. CONCLUSION: New algorithms and guidance have been established to improve care with the use of intrathecal drug delivery.

The Polyanalgesic Consensus Conference (PACC): Recommendations for Trialing of Intrathecal Drug Delivery Infusion Therapy.

INTRODUCTION: Intrathecal (IT) drug infusion is an appropriate and necessary tool in the algorithm to treat refractory cancer and noncancer pain. The decision-making steps/methodology for selecting appropriate patients for implanted targeted drug delivery systems is controversial and complicated. Therefore, a consensus on best practices for determining appropriate use of IT drug infusion may involve testing/trialing this therapy before implantation. METHODS: This current Polyanalgesic Consensus Conference (PACC) update was designed to address the deficiencies and emerging innovations since the previous PACC convened in 2012. A literature search identified publications available since the previous PACC publications in 2014, and relevant sources were contributed by the PACC members. After reviewing the literature, the panel determined the evidence levels and degrees of recommendations. The developed consensus was ranked as strong (>80%), moderate (50-79%), or weak (<49%). RESULTS: The trialing for IT drug delivery systems (IDDS) remains an area of continued controversy. The PACC recommendations for trialing are presented in 34 consensus points and cover trialing for morphine, ziconotide, and medication admixtures; starting doses and titration practices; measurements of success; trial settings and monitoring; management of systemic opioids during trialing; and the role of psychological evaluation. Finally, the PACC describes clinical scenarios in which IT trialing is required or not required. CONCLUSION: The PACC provides consensus guidance on best practices of trialing for IDDS implants. In addition, the PACC recommends that no trial may be required in certain patient populations.

The Polyanalgesic Consensus Conference (PACC): Recommendations for Intrathecal Drug Delivery: Guidance for Improving Safety and Mitigating Risks.

INTRODUCTION: Intrathecal therapy is an important part of the pain treatment algorithm for chronic disease states. The use of this option is a viable treatment strategy, but it is inherent for pain physicians to understand risk assessment and mitigation. In this manuscript, we explore evidence and mitigating strategies to improve safety with intrathecal therapy. METHODS: A robust literature search was performed covering January 2011 to October 9, 2016, in PubMed, Embase, MEDLINE, Biomed Central, Google Scholar, Current Contents Connect, and International Pharmaceutical Abstracts. The information was cross-referenced and compiled for evidence, analysis, and consensus review, with the intent to offer weighted recommendations and consensus statements on safety for targeted intrathecal therapy delivery. RESULTS: The Polyanalgesic Consensus Conference has made several best practice recommendations to improve care and reduce morbidity and mortality associated with intrathecal therapy through all phases of management. The United States Prevention Service Task Force evidence level and consensus strength assessments are offered for each recommendation. CONCLUSION: Intrathecal therapy is a viable and relatively safe option for the treatment of cancer- and noncancer-related pain. Continued research and expert opinion are required to improve our current pharmacokinetic and pharmacodynamic model of intrathecal drug delivery, as this will undoubtedly improve safety and efficacy.

Clinical Uses of Intrathecal Therapy and Its Placement in the Pain Care Algorithm.

Intrathecal drug delivery is an effective treatment option for patients with severe chronic pain who have not obtained adequate analgesia from more conservative therapies (eg, physical therapy, systemic opioids, nonsteroidal anti-inflammatory drugs, antidepressants, and anticonvulsants). This review focuses on, but is not limited to, the 2 agents currently approved by the U.S. Food and Drug Administration for intrathecal analgesia: preservative-free morphine and ziconotide (a nonopioid, selective N-type calcium channel blocker). We describe the appropriate use of intrathecal therapy in the management of severe chronic pain, based on current best practices. Topics addressed here include patient selection, trialing, dosing and titration, adverse event profiles, long-term management, intrathecal therapy for cancer-related pain, and the placement of intrathecal therapy in the pain care algorithm. In appropriately selected patients with chronic pain, intrathecal therapy can provide substantial pain relief with improved functioning and quality of life. Successful long-term management requires ongoing patient monitoring for changes in efficacy and the occurrence of adverse events, with subsequent changes in intrathecal dosing and titration, the addition of adjuvant intrathecal agents, and the use of concomitant oral medications to address side effects, as needed. Based on an infrequent but clinically concerning risk of overdose, granuloma, and other opioid-induced complications, nonopioid therapy with ziconotide may be preferred as a first-line intrathecal therapy in patients without a history of psychosis or allergy.

Peripheral Nerve Stimulation for Pain in Extremities: An Update.

Pain in extremities may occur in a variety of central and peripheral neuropathic and nociceptive syndromes, some of which may respond to central neuromodulation procedures. Peripheral neuromodulation techniques, either as a stand-alone therapy or as an adjuvant to spinal cord stimulation, may be particularly effective when the pain is localized to a part of a single extremity or when the source of the pain is related to the malfunction of a known peripheral nerve. Further, peripheral neuromodulation is used to treat disorders in which central simulation fails to provide discrete therapeutic paresthesia. Despite the fact that there are only a few neuromodulatory devices designed specifically for the periphery, clinical experiences are growing, and here we provide a clinical update on use of peripheral nerve stimulation (PNS) in management of chronic pain in extremities. Historical PNS strategies and innovative methods are reviewed and highlighted in this chapter. With the upcoming technological advances and new stimulation paradigms, along with clear updated guidelines statements, the utilization of PNS will likely continue to increase and improve the management of chronic pain syndromes in the extremities. The potential success of the novel devices specifically designed to target the peripheral nervous system is expected to positively impact and promote the use of PNS in treatment of chronic pain.

Intrathecal drug delivery for pain: a clinical guide and future directions.

Intrathecal infusion of medications allows for a direct delivery of agents to the receptors in which they act. This method of treatment is indicated in severe chronic pain of cancer or noncancer origin. In recent years, the use of these devices has increased and the general pain physician, referring doctor and concerned parties such as insurers, needs a better understanding of safety and efficacy. This article is an overview of this therapeutic option and also provides an update on new innovations and forward thinking approaches at improving patient selection and appropriateness of use.

Intrathecal Pharmacology Update: Novel Dosing Strategy for Intrathecal Monotherapy Ziconotide on Efficacy and Sustainability.

INTRODUCTION: Intrathecal drug delivery is a well-defined strategy to treat malignant and nonmalignant pain. Ziconotide is a well-studied intrathecal medicine option that has many attractive qualities, as it is non-granulomagenic, overdose or underdose is not associated with cardiopulmonary compromise or death, and is a non-opoid analgesic. However, it has had slow adoption into pain care algorithms because it has been historically plagued with the connotation of having a narrow therapeutic window and a low sustainability rate. We introduce a novel dosing strategy to improve patient outcomes and sustainability. METHODS: Patients were identified as being an intrathecal candidate and trialed with ziconotide based on the current standard of care. Patient demographics, diagnosis, previous treatment failures, and pre-implant visual analog scale (VAS) scores were recorded. Once the trial was deemed successful, based on the dual bolusing strategy, the patient underwent device implantation. Consecutive patients were prospectively followed. Ziconotide was then initiated with a flex dosing strategy, weighted during nocturnal dosing. Outcome endpoints included: reduction in VAS, side effects, durability of therapy, and systemic opioid use prior to implant and at last visit were noted (calculated to daily morphine equivalents). Primary endpoint was tolerability of ziconotide at three months following new dosing strategy. No industry support or funding was obtained for this project. RESULTS: All enrolled patients met the endpoint of the study of tolerability of ziconotide at three months. Numbers declined to 75% of patients at four months, and 70% of patients at six months. The discontinuing side-effects were most commonly urinary retention and visual hallucinations. There were no serious adverse events and no unresolved complications reported. Numerical rating scale (NRS) decreased on average from 9.06 to 1.8. Opioid reduction in morphine equivalents averaged 91.5% DISCUSSION: The efficacy and tolerability of monotherapy ziconotide may be improved by using a weighted bolus flex dosing strategy as compared with slow continuous infusions. CONCLUSION: We present a novel strategy to deliver ziconotide using a unique continuous infusion flex dosing strategy. Further randomized, prospective, higher-powered studies are needed to critically evaluate the conclusions suggested by this limited prospective case series.

The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the Neuromodulation Appropriateness Consensus Committee.

INTRODUCTION: The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications. METHODS: The NACC used literature reviews, expert opinion, clinical experience, and individual research. Authors consulted the Practice Parameters for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain (2006), systematic reviews (1984 to 2013), and prospective and randomized controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google Scholar. RESULTS: Neurostimulation is relatively safe because of its minimally invasive and reversible characteristics. Comparison with medical management is difficult, as patients considered for neurostimulation have failed conservative management. Unlike alternative therapies, neurostimulation is not associated with medication-related side effects and has enduring effect. Device-related complications are not uncommon; however, the incidence is becoming less frequent as technology progresses and surgical skills improve. Randomized controlled studies support the efficacy of spinal cord stimulation in treating failed back surgery syndrome and complex regional pain syndrome. Similar studies of neurostimulation for peripheral neuropathic pain, postamputation pain, postherpetic neuralgia, and other causes of nerve injury are needed. International guidelines recommend spinal cord stimulation to treat refractory angina; other indications, such as congestive heart failure, are being investigated. CONCLUSIONS: Appropriate neurostimulation is safe and effective in some chronic pain conditions. Technological refinements and clinical evidence will continue to expand its use. The NACC seeks to facilitate the efficacy and safety of neurostimulation.

The appropriate use of neurostimulation: new and evolving neurostimulation therapies and applicable treatment for chronic pain and selected disease states. Neuromodulation Appropriateness Consensus Committee.

INTRODUCTION: The International Neuromodulation Society (INS) has determined that there is a need to provide an expert consensus that defines the appropriate use of neuromodulation technologies for appropriate patients. The Neuromodulation Appropriateness Consensus Committee (NACC) was formed to give guidance to current practice and insight into future developments. METHODS: The INS executive board selected members of the international scientific community to analyze scientific evidence for current and future innovations and to use clinical experience to fill in any gaps in information. The NACC used PubMed and Google Scholar to obtain current evidence in the field and used clinical and research experience to give a more complete picture of the innovations in the field. RESULTS: The NACC has determined that currently approved neurostimulation techniques and technologies have expanded our ability to treat patients in a more effective and specific fashion. Despite these advances, the NACC has identified several additional promising technologies and potential applications for neurostimulation that could move this field forward and expand the applicability of neuromodulation. CONCLUSIONS: The NACC concludes that the field of neurostimulation is an evolving and rapidly changing one that will lead to improved patient access, safety, and outcomes.