Mark S Wallace

Cedars-Sinai Medical Center, Los Angeles, California, United States

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Publications (99)339.55 Total impact

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    ABSTRACT: to assess the long-term safety, tolerability, and consistency of effect of fentanyl pectin nasal spray (FPNS) in patients with breakthrough cancer pain (BTCP). a multicenter, open-label study. patients with chronic cancer pain treated with > or = 60 mg/d oral morphine or equivalent experiencing 1-4 episodes per day of BTCP. all patients entered into a 16-week treatment phase after undergoing a dose-titration phase with FPNS. safety and tolerability were assessed by adverse events (AEs) and by nasal tolerability assessments. Consistency of effect was monitored through additional rescue medication use and FPNS dose change. four hundred three patients were included in the safety analyses. Of these, 356 patients entered the treatment phase and 110 patients completed the study. FPNS was self-administered for 42,227 episodes. During the treatment phase, 99 patients (24.6 percent) reported treatment-related AEs; most were mild or moderate and typical of opioids. Serious AEs were reported by 61 patients (15.1 percent), but only five were considered related to study drug. Of the 80 deaths that occurred during this study, one was assessed as possibly related to study drug. Nasal assessments revealed no significant local effects. No additional rescue medication was required after 94 percent of FPNS-treated episodes. More than 90 percent of patients required no increase in their initial dose of FPNS. FPNS use for BTCP was associated with AEs, typical of opioids, with no evidence of nasal toxicity. A large proportion of BTCP episodes were treated with a single dose, and doses remained stable over the 4-month period.
    Journal of opioid management 01/2010; 6(5):319-28.
  • James G Modir, Mark S Wallace
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    ABSTRACT: The heat/capsaicin sensitization and intradermal capsaicin injection models are safe and noninvasive paradigms to generate stable, long-lasting, and reproducible injury capable of producing an area of both primary and secondary hyperalgesia. Risk of skin injury is substantially reduced since lower levels of thermal and chemical irritation produce long-lasting cutaneous hyperalgesia. Rekindling sustains central sensitization by providing peripheral nociceptive input. The intradermal capsaicin model has been widely used to test analgesic efficacy for a wide range of analgesics. Unlike the heat/capsaicin sensitization model, intradermal capsaicin results in a brief painful stimulus followed by a long lasting area of secondary hyperalgesia. The intradermal injection of capsaicin results in a transient, intense stinging sensation at the site of injection (e.g. heat allodynia) followed by a persistent area of secondary tactile allodynia.
    Methods in molecular biology (Clifton, N.J.) 01/2010; 617:169-74. · 1.29 Impact Factor
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    ABSTRACT: Morphine is often administered by the subcutaneous (SC) route when venous access is difficult to achieve. Hyaluronidase temporarily increases the permeability of SC connective tissues by degrading hyaluronan and has been shown to increase the dispersion and absorption of coadministered molecules. Therefore, hyaluronidase could enhance the pharmacokinetics of subcutaneous morphine. This Phase IIIB, double-blind, randomized, placebo-controlled crossover study compared the pharmacokinetics, safety, and tolerability of morphine administered SC with and without 150U of recombinant human hyaluronidase (rHuPH20) with those of intravenous (IV) morphine administration in 13 patients in a hospice or palliative care setting. Each patient received morphine 5mg parenterally daily for three days by a different method each day: IV, SC plus rHuPH20, and SC plus placebo (normal saline). The primary endpoint was the time to maximum plasma concentration (T(max)) for morphine. Concomitant SC administration of rHuPH20 enhanced the absorption rate of morphine compared with SC morphine with placebo, significantly reducing the mean T(max) from 13.8 to 9.2 minutes, a 33% decrease (P=0.026). The respective values for geometric mean maximum plasma concentration were 94.9 and 107.5nmol/L, a 13% increase (P=0.024), and the area under the plasma concentration vs. time curve values were 7.7 and 7.2micromol x min/L (P=0.23). Morphine plus rHuPH20 appeared to be safe and well tolerated. In patients requiring opioid analgesia, SC morphine plus rHuPH20 provides pharmacokinetic characteristics that are superior to those of SC morphine alone. These positive results warrant further studies on analgesic efficacy of morphine delivered with rHuPH20.
    Journal of pain and symptom management 10/2009; 38(5):663-72. · 2.42 Impact Factor
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    ABSTRACT: Neuropathic pain disorders are usually characterized by spontaneous ongoing or intermittent symptoms, stimulus-evoked positive sensory phenomena, and negative sensory phenomena. Spontaneous individual subject specific phenomena are identified in the neurologic history and are quantifiable by means of self-reported neuropathic pain symptoms tools such as scales, inventories, and questionnaires. Negative and positive sensory phenomena are assessed by the neurologic bedside examination and quantitative sensory testing (QST), which refers to psychophysical tests of sensory perception during the administration of stimuli with predetermined physical properties and following specific protocols. QST is able to capture and quantify stimulus-evoked negative and positive sensory phenomena, and as such should become standard if not a critical tool in neuropathic pain research and practice. Although the advent of anatomic and functional imaging modalities is revolutionizing our understanding of the mechanisms of neuropathic pain, only by anchoring such test results to individual subjects' own perceptions via QST can they provide meaningful information about neuropathic pain, which is based on perceptual experience. To yield useful results, QST requires a cooperative subject and carefully standardized methods, including standardization of the stimulus parameters as well as the testing environment, instructions, and evaluation methods. This manuscript provides a concise review of fundamental concepts necessary for understanding the role of QST in the process of eliciting information about sensory abnormalities associated with neuropathic pain and the place of that information in analysis of pain mechanisms. Together with the companion manuscript, this review provides definitions that should help further the use of QST as a diagnostic tool as well.
    The Clinical journal of pain 10/2009; 25(7):641-7. · 3.01 Impact Factor
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    ABSTRACT: Despite a growing interest in neuropathic pain, neurologists and pain specialists do not have a standard, validated, office examination for the evaluation of neuropathic pain signs to complement the neurologic, musculoskeletal, and general physical examinations. An office neuropathic pain examination focused on quantifying sensory features of neuropathic pain, ranging from deficits to allodynia and hyperalgesia, and evoked by a physiologically representative array of stimuli, will be an essential tool to monitor treatment effectiveness and for clinical investigation into the mechanisms and management of neuropathic pain. Such an examination should include mapping of areas of stimulus-evoked neuropathic pain and standardized, reproducible quantitative sensory testing (QST) of tactile, punctuate, pressure, and thermal modalities. We review quantitative sensory testing methodology in general and specific tests for the evaluation of neuropathic pain phenomena. Numerous quantitative sensory testing techniques for dynamic mechanical, pressure, vibration, and thermal sensory testing and mapping have been described. We propose a comprehensive neuropathic pain evaluation protocol that is based upon these available techniques. A comprehensive neuropathic pain evaluation protocol is essential for further advancement of clinical research in neuropathic pain. A protocol that uses tools readily available in clinical practice, when established and validated, can be used widely and thus accelerate data collection for clinical research and increase clinical awareness of the features of neuropathic pain.
    The Clinical journal of pain 10/2009; 25(7):632-40. · 3.01 Impact Factor
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    ABSTRACT: Neuropathic pain is a considerable burden that affects activities of daily living. The management of neuropathic pain can be challenging because of multiple etiologies and complex manifestations. Ziconotide is a nonopioid intrathecal (IT) analgesic option for patients with neuropathic pain refractory to conventional treatments. The objective of this article is to review the published literature on ziconotide for the treatment of neuropathic pain. Relevant publications were identified through searches of all years of 6 databases, which included PubMed, EMBASE, and CINAHL. Search terms used were ziconotide, SNX-111, MVIIA, Prialt, and neuropathic pain. Publications were included if ziconotide was intrathecally administered (either alone or in combination with other IT agents) to treat neuropathic pain of any etiology and if pain assessment was an outcome measure. Data extracted included study design, IT drug doses, pain outcome measures, and adverse events (AEs). Twenty-eight articles met the inclusion criteria: 5 were preclinical studies and 23 were clinical studies. In the preclinical studies, ziconotide demonstrated antiallodynic effects on neuropathic pain. Data from double-blind, placebo-controlled (DBPC) trials indicated that patients with neuropathic pain reported a mean percent improvement in pain score with ziconotide monotherapy that ranged from 15.7% to 31.6%. A low starting dose and slow titration of ziconotide resulted in an improved safety profile in the aforementioned trials. Common AEs associated with ziconotide include nausea and/or vomiting, dizziness, confusion, urinary retention, and somnolence. Evidence from DBPC trials, open-label studies, case series, and case studies suggests that ziconotide, as either monotherapy or in combination with other IT drugs, is a potential therapeutic option for patients with refractory neuropathic pain. Additional studies are needed to establish the long-term efficacy and safety of ziconotide for neuropathic pain.
    Pain Practice 09/2009; 9(5):327-37. · 2.61 Impact Factor
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    ABSTRACT: Prospective in vivo experimental animal model. To determine the effect of intra-arterial injection of the steroids commonly used for transforaminal epidurals on the central nervous system. And to determine if all of the steroids have the same effect. SUMMARY OF BACKGROUND DATA.: Transforaminal epidural steroid injection is commonly employed to treat radicular pain. This approach is associated with complications, including stroke and death. While the mechanism is unknown, the leading hypothesis is that intravascular injection of particulate steroids leads to microembolization. To characterize the nature of steroid induced injury, a rodent model was employed. The internal carotid artery was dissected and its branches ligated. The external carotid artery was ligated, mobilized, cannulated, and injectate administered. Five solutions were tested: Depo-Medrol (N = 11), Depo-Medrol carrier (N = 6), Solu-Medrol (N = 6), Decadron (N = 8), and normal saline (N = 7). Drugs, in volume of 50 microL, were injected into the ICA via the ECA cannula at 25 microL/min. The extent of central nervous system injury was evaluated by analysis of coronal sections of the brain. Cerebral hemorrhage occurred in test subjects with the following frequency: 8 of 11 in the Depo-Medrol group, 7 of 8 in the Solu-Medrol group, and 3 of 6 in the Depo-Medrol carrier group; no lesions were identified in the Decadron or saline groups (P < 0.01). Evan's blue dye leakage was detected in the Depo-Medrol and Solu-Medrol groups, but not the Decadron or saline groups. This study presents the first in vivo evaluation of intra-arterial steroid injection. Data demonstrate Depo-Medrol, as well as its nonparticulate carrier, and Solu-Medrol can produce significant injury to the blood-brain barrier when injected intra-arterially. These results demonstrate that injury is produced not only by particulate obstruction of the cerebral microvasculature, but also by toxicity of the carrier or steroid (methylprednisolone).
    Spine 07/2009; 34(16):1638-43. · 2.16 Impact Factor
  • Tobias Moeller-Bertram, Mark S. Wallace
    Current Pain and Headache Reports 01/2009; 13(3):179-180. · 1.67 Impact Factor
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    ABSTRACT: The limitations of current treatments for postherpetic neuralgia (PHN) have led to the investigation of localised, non-systemic alternatives. NGX-4010, a high-concentration (8%) capsaicin dermal patch, was developed to treat patients with neuropathic pain. We report the results of a randomised, double blind, 12-week study of the efficacy and safety of one application of NGX-4010 in patients with PHN. In this multicentre, double-blind, parallel-group trial, 402 patients were randomly assigned to one 60-min application of NGX-4010 (640 microg/cm(2) [8% capsaicin]) or a low-concentration capsaicin control patch (3.2 microg/cm(2) [0.04% capsaicin]). Patients were aged 18-90 years, had had postherpetic neuralgia for at least 6 months, and had an average baseline numeric pain rating scale (NPRS) score of 3 to 9. The primary efficacy endpoint was percentage change in NPRS score from baseline to weeks two to eight. Analysis was by intention to treat. This trial is registered with, number NCT00115310. Patients who were randomly assigned to NGX-4010 (n=206) had a significantly greater reduction in pain during weeks two to eight than did patients who had the control patch (n=196). The mean changes in NPRS score were -29.6%vs -19.9% (difference -9.7%, 95% CI -15.47 to -3.95; p=0.001). 87 (42%) patients who received NGX-4010 and 63 (32%) controls had a 30% or greater reduction in mean NPRS score (odds ratio [OR] 1.56, 95% CI 1.03 to 2.37; p=0.03). The patients who had NGX-4010 had significant improvements in pain during weeks two to 12 (mean change in NPRS score -29.9%vs -20.4%, difference -9.5, -15.39 to -3.61; p=0.002). Transient blood pressure changes associated with changes in pain level were recorded on the day of treatment, and short-lasting erythema and pain at the site of application were common, self-limited, and generally mild to moderate in the NGX-4010 group and less frequent and severe in the controls. One 60-min application of NGX-4010 provided rapid and sustained pain relief in patients with postherpetic neuralgia. No adverse events were associated with treatment except for local reactions at the site of application and those related to treatment-associated pain.
    The Lancet Neurology 01/2009; 7(12):1106-12. · 23.92 Impact Factor
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    ABSTRACT: To determine the efficacy and safety of a gastric-retentive, extended-release gabapentin (gabapentin ER) taken once or twice daily for treatment of postherpetic neuralgia. Using an enrichment design, a randomized, double-blind, placebo-controlled study was conducted in 158 patients who had experienced pain for at least 3 months after healing of acute herpes zoster skin rash and who had a baseline average daily pain (ADP) score of > or =4 on a 0 to 10 Numerical Rating Scale. Patients received gabapentin ER either once daily (1800 mg PM) or twice daily (600 mg AM, 1200 mg PM) or placebo for 4 weeks. Efficacy measures included changes from baseline to end point in ADP score and average daily sleep interference score. Mean (SEM) changes for ADP score were -1.93 (0.28), -2.24 (0.29), and -1.29 (0.29) in the gabapentin ER once daily, twice daily, and placebo groups, respectively (P=0.089 and 0.014 for gabapentin ER once daily and twice daily, respectively, vs. placebo), with 25.5%, 28.8%, and 11.8% of patients, respectively, reporting > or =50% decrease from baseline in ADP score. Mean (SEM) changes in sleep interference scores were -1.94 (0.30), -2.28 (0.30), and -1.16 (0.30), respectively (P=0.048 and 0.006 for gabapentin ER once daily and twice daily, respectively, vs. placebo). Common adverse events in the gabapentin ER once daily, twice daily, and placebo groups, respectively, were dizziness (22.2%, 11.3%, and 9.8%) and somnolence (9.3%, 7.5%, and 7.8%). Gabapentin ER administered twice daily is effective and safe for the treatment of pain associated with postherpetic neuralgia.
    The Clinical journal of pain 01/2009; 25(3):185-92. · 3.01 Impact Factor
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    ABSTRACT: This open-label multicenter study evaluated the long-term safety and efficacy of intrathecal ziconotide and included 78 patients with chronic pain who had completed one of two previous ziconotide clinical trials. Each patient's initial ziconotide dose was based on his or her dose from the study of origin and was adjusted as necessary on the basis of adverse events and analgesic effect. The median ziconotide dose was 6.48 mcg/day (range, 0.00-120.00 mcg/day) at the Initial Visit and ranged from 5.52 to 7.20 mcg/day across all study visits. The most commonly reported new adverse events that were considered ziconotide related were memory impairment (11.3%); dizziness, nystagmus, and speech disorder (8.5% each); nervousness and somnolence (7.0% each); and abnormal gait (5.6%). There was no evidence of increased adverse event incidence at higher cumulative ziconotide doses. Elevations in creatine kinase were noted, but the proportion of patients with creatine kinase elevations did not change from the Initial Visit to the Termination Visit (4.1% each). Stable mean Visual Analog Scale of Pain Intensity scores during the three years of the study suggested no evidence of increased pain intensity with increased duration of ziconotide exposure. Long-term treatment with ziconotide appeared to be well tolerated and effective in patients whose response to ziconotide and ability to tolerate the drug had been previously demonstrated.
    Journal of pain and symptom management 09/2008; 37(3):363-72. · 2.42 Impact Factor
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    ABSTRACT: To assess the safety and efficacy of adding intrathecal ziconotide to intrathecal morphine in patients being treated with a stable intrathecal morphine dose. Phase II, multicenter, open-label study with a 5-week titration phase and an extension phase. Outpatient clinics. Patients with suboptimal pain relief receiving stable intrathecal morphine doses (2-20 mg/day). Intrathecal morphine dosing remained constant during the titration phase. Ziconotide therapy began at 0.60 microg/day and was titrated to a maximum of 7.2 microg/day. During the extension phase, ziconotide and intrathecal morphine dosing were adjusted at the investigator's discretion. Safety was assessed primarily via adverse event reports. Efficacy was analyzed via percentage change on the visual analog scale of pain intensity and in weekly systemic opioid consumption. Twenty-six patients were enrolled. Treatment-emergent adverse events were generally mild or moderate; the most common (> or = 15% of patients in either study phase) study drug-related (i.e., ziconotide/morphine combination [or ziconotide monotherapy in the extension phase only]) events were confusion, dizziness, abnormal gait, hallucinations, and anxiety. The mean percentage improvement in visual analog scale of pain intensity scores was 14.5% (95% confidence interval: -9.4% to 38.5%) from baseline to week 5 and varied during the extension phase (range: -0.4% to 42.8%). Mean percentage change from baseline in systemic opioid consumption was -14.3% at week 5 and varied considerably during the extension phase. Ziconotide, combined with stable intrathecal morphine, may reduce pain and decrease systemic opioid use in patients with pain inadequately controlled by intrathecal morphine alone.
    Pain Medicine 04/2008; 9(3):271-81. · 2.46 Impact Factor
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    ABSTRACT: Background.  Expert panel of physicians and nonphysicians, all expert in intrathecal (IT) therapies, convened in the years 2000 and 2003 to make recommendations for the rational use of IT analgesics based on the preclinical and clinical literature known up to those times, presentations of the expert panel, discussions on current practice and standards, and the result of surveys of physicians using IT agents. An expert panel of physicians and convened in 2007 to review previous recommendations and to form recommendations for the rational use of IT agents as they pertain to new scientific and clinical information regarding the etiology, prevention and treatment for IT granuloma. Method.  A review of preclinical and clinical literature from 2000 to 2006 was undertaken and disseminated to an expert panel of physicians. Focused discussions concerning the rational use of IT agents and its relationship to the etiology of, prevention of, and treatment of IT granuloma were held. Results.  This report presents here new knowledge of the etiology of catheter tip granuloma and guidelines for its prevention and treatment.
    Neuromodulation 04/2008; 11(2):77-91. · 1.19 Impact Factor
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    ABSTRACT: Background.  Expert panels of physicians and nonphysicians, all expert in intrathecal (IT) therapies, convened in the years 2000 and 2003 to make recommendations for the rational use of IT analgesics, based on the preclinical and clinical literature known up to those times, presentations of the expert panels, discussions on current practice and standards, and the result of surveys of physicians using IT agents. An expert panel of physicians and nonphysicians has convened in 2007 to update information known regarding IT therapies and to update information on new and novel opioid and nonopioid analgesic compounds that might show promise for IT use. Methods.  A review of preclinical and clinical published relevant studies from 2000 to 2006 was undertaken and disseminated to a convened expert panel of physicians and nonphysicians to discuss new and novel analgesic agents for IT use. Results.  The panelists identified several agents that were worthy of future studies for the clinical and rational use of IT agents that are presented in this article. Conclusions.  A list of nonopioid IT analgesics, including gabapentin, adenosine, octreotide, the χ-conopeptide, Xen2174, the conopeptide, neurotensis 1 agonist, CGX-1160, the ω-conotoxin, AM-336, and physostigmine, were identified as worthy of future research by the panelists.
    Neuromodulation 04/2008; 11(2):92-97. · 1.19 Impact Factor
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    ABSTRACT: Ziconotide is a non-opioid drug indicated for management of severe chronic pain in patients for whom intrathecal (IT) therapy is warranted and who are intolerant of or refractory to other treatments. Six-hundred and forty-four patients with severe chronic pain participated in this open-label, multicenter study. Ziconotide titration was followed by long-term infusion. Efficacy assessments included the Visual Analog Scale of Pain Intensity. Safety was assessed via adverse events (AEs), vital signs, and routine laboratory values. One-hundred and nineteen patients received ziconotide for > or = 360 days; total exposure was 350.9 patient years. Median duration of ziconotide therapy was 67.5 days (range, 1.2-1215.5 days); mean dose at last infusion was 8.4 microg/d (range, 0.048-240.0 microg/d). Median Visual Analog Scale of Pain Intensity scores at baseline, month 1, and the last available observation up to month 2 were 76 mm (range, 4-100 mm), 68 mm (range, 0-100 mm), and 73 mm (range, 0-100 mm), respectively. Most patients (99.7%) experienced > or = 1 AE. Most AEs were of mild (43.5%) or moderate (42.3%) severity; 58.6% of AEs were considered unrelated to ziconotide. The most commonly reported AEs (> or = 25% of patients) included nausea, dizziness, headache, confusion, pain, somnolence, and memory impairment. Clinically significant abnormalities (> 3 times the upper limit of normal) in creatine kinase levels were reported in 0.9% of patients at baseline, 5.7% at month 1, and 3.4% at ziconotide discontinuation. No drug-related deaths, IT granulomas, or permanent adverse sequelae occurred with ziconotide therapy. We conclude that long-term IT ziconotide is an option for patients with severe, refractory chronic pain.
    Anesthesia and analgesia 03/2008; 106(2):628-37, table of contents. · 3.08 Impact Factor
  • Mark S Wallace, Gery Schulteis
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    ABSTRACT: There is an abundance of literature on the efficacy of gabapentin for the treatment of neuropathic pain. Two studies have demonstrated an effect of a single dose of gabapentin on experimental cutaneous hyperalgesia. This study evaluated the effect of chronic delivery of oral gabapentin on experimentally induced cutaneous hyperalgesia. A randomized, double-blinded, placebo-controlled crossover design methodology was conducted. Participants took part in two 10-day study sessions, separated by a 7-day washout period. One session was with gabapentin and one with placebo. Study drug was administered 300 mg b.i.d. from day 1 to 3, 300 mg q.i.d. from day 4 to 6 and 600 mg t.i.d. from day 7 to 10. At baseline, day 4, day 7, and day 10, quantitative sensory testing was performed to thermal and mechanical stimuli. On day 10, only intradermal capsaicin was injected on the volar aspect of the forearm followed by an assessment of pain and hyperalgesia. Side effects were recorded by the participants each evening. Thirteen participants were enrolled into the study. Three dropped out because of intolerable side effects. Ten participants completed the study and were able to tolerate the highest dose of gabapentin. Oral gabapentin had no significant effect on acute sensory thresholds, pain, secondary hyperalgesia, or flare response induced by intradermal capsaicin. There were significantly more side effects associated with gabapentin with sedation and dizziness being the most common. This study demonstrated a lack of effect of the chronic delivery of oral gabapentin on experimentally induced cutaneous hyperalgesia. The discrepancy of this finding with other studies using single oral doses may be the result of differences in the models used and differences in drug kinetics and plasma levels. The results of this study do not correlate with the clinical studies on gabapentin, which demonstrate efficacy at 1800 mg/d.
    The Clinical journal of pain 01/2008; 24(6):544-9. · 3.01 Impact Factor
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    ABSTRACT: Objectives.  This study aims to assess the safety and efficacy of long-term intrathecal (IT) ziconotide infusion. Materials and Methods.  In this prospective study, 155 patients with severe chronic pain (48 with malignant pain, 107 with nonmalignant pain) who had been responsive to short-term IT ziconotide in a double-blind, placebo-controlled study received long-term, open-label IT ziconotide monotherapy. Efficacy assessments included the mean percentage change on the visual analog scale of pain intensity from baseline in the study of origin; safety was monitored by adverse event (AE) reports, periodic laboratory tests, and vital sign measurements. Results.  At the last available observation, the visual analog scale of pain intensity scores had decreased by a mean of 36.9% from baseline in the short-term trial (N = 144; 95% CI: 30.1-43.7%; p < 0.0001). The mean IT ziconotide dose remained stable over 12 months in the 31 patients who participated in the study for ≥ one year. Ziconotide-related AEs were reported in 147 out of 155 patients (94.8%); 39.4% of patients discontinued treatment because of AEs, the majority of which were considered ziconotide related. Conclusions.  Ziconotide IT monotherapy provided patients with analgesia for 12 months in this open-label study, with an acceptable benefit/risk profile and no evidence of tolerance.
    Neuromodulation 01/2008; 11(1):40-49. · 1.19 Impact Factor
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    ABSTRACT: Patients with neuropathic pain (NP) are challenging to manage and evidence-based clinical recommendations for pharmacologic management are needed. Systematic literature reviews, randomized clinical trials, and existing guidelines were evaluated at a consensus meeting. Medications were considered for recommendation if their efficacy was supported by at least one methodologically-sound, randomized clinical trial (RCT) demonstrating superiority to placebo or a relevant comparison treatment. Recommendations were based on the amount and consistency of evidence, degree of efficacy, safety, and clinical experience of the authors. Available RCTs typically evaluated chronic NP of moderate to severe intensity. Recommended first-line treatments include certain antidepressants (i.e., tricyclic antidepressants and dual reuptake inhibitors of both serotonin and norepinephrine), calcium channel alpha2-delta ligands (i.e., gabapentin and pregabalin), and topical lidocaine. Opioid analgesics and tramadol are recommended as generally second-line treatments that can be considered for first-line use in select clinical circumstances. Other medications that would generally be used as third-line treatments but that could also be used as second-line treatments in some circumstances include certain antiepileptic and antidepressant medications, mexiletine, N-methyl-D-aspartate receptor antagonists, and topical capsaicin. Medication selection should be individualized, considering side effects, potential beneficial or deleterious effects on comorbidities, and whether prompt onset of pain relief is necessary. To date, no medications have demonstrated efficacy in lumbosacral radiculopathy, which is probably the most common type of NP. Long-term studies, head-to-head comparisons between medications, studies involving combinations of medications, and RCTs examining treatment of central NP are lacking and should be a priority for future research.
    Pain 01/2008; 132(3):237-51. · 5.64 Impact Factor
  • Journal of Pain - J PAIN. 01/2008; 9(4):46-46.
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    ABSTRACT: Although the preclinical literature suggests that cannabinoids produce antinociception and antihyperalgesic effects, efficacy in the human pain state remains unclear. Using a human experimental pain model, the authors hypothesized that inhaled cannabis would reduce the pain and hyperalgesia induced by intradermal capsaicin. In a randomized, double-blinded, placebo-controlled, crossover trial in 15 healthy volunteers, the authors evaluated concentration-response effects of low-, medium-, and high-dose smoked cannabis (respectively 2%, 4%, and 8% 9-delta-tetrahydrocannabinol by weight) on pain and cutaneous hyperalgesia induced by intradermal capsaicin. Capsaicin was injected into opposite forearms 5 and 45 min after drug exposure, and pain, hyperalgesia, tetrahydrocannabinol plasma levels, and side effects were assessed. Five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 min after cannabis exposure, however, there was a significant decrease in capsaicin-induced pain with the medium dose and a significant increase in capsaicin-induced pain with the high dose. There was no effect seen with the low dose, nor was there an effect on the area of hyperalgesia at any dose. Significant negative correlations between pain perception and plasma delta-9-tetrahydrocannabinol levels were found after adjusting for the overall dose effects. There was no significant difference in performance on the neuropsychological tests. This study suggests that there is a window of modest analgesia for smoked cannabis, with lower doses decreasing pain and higher doses increasing pain.
    Anesthesiology 12/2007; 107(5):785-96. · 5.16 Impact Factor

Publication Stats

3k Citations
339.55 Total Impact Points


  • 2013
    • Cedars-Sinai Medical Center
      • Cedars Sinai Medical Center
      Los Angeles, California, United States
  • 1997–2013
    • University of California, San Diego
      • • Department of Anesthesiology
      • • Department of Medicine
      San Diego, CA, United States
  • 2012
    • VA San Diego Healthcare System
      San Diego, California, United States
  • 2010
    • Beth Israel Medical Center
      • Department of Pain Medicine and Palliative Care
      New York City, New York, United States
  • 2009
    • Swedish Medical Center Seattle
      Seattle, Washington, United States
  • 2008
    • University of Rochester
      Rochester, New York, United States
    • North Carolina Clinical Research
      Raleigh, North Carolina, United States
    • La Jolla Pharmaceutical
      San Diego, California, United States