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J Voirin, I Darie, D Fischer, A Simon, I Rohmer-Heitz, F Proust
INTRODUCTION: Motor cortex stimulation is a well-known treatment modality for refractory neuropathic pain. Nevertheless, some cases of therapeutic failure have been described but alternative therapies for these cases are rarely reported. CASE REPORT: The patient presented with neuropathic pain in his right arm due to a cervical syrinx which was surgically treated by a shunt in 2003 with no clinical improvement. As alternative therapy, after an evaluation by repetitive magnetic transcranial stimulation with significant benefit, motor cortex stimulation was successfully implanted in 2004...
October 19, 2016: Neuro-Chirurgie
Julia Prusik, Charles Argoff, Sophia Peng, Julie G Pilitsis
BACKGROUND: Ziconotide use in intrathecal drug therapy (IDT) has been limited by dosing related side effects. We examine our experience with ziconotide as a first line IDT monotherapy in patients with chronic pain and present our low and slow dosing algorithm aimed at reducing these patient experienced side effects while adequately managing pain. METHODS: We retrospectively reviewed demographics, dosing, and outcomes of 15 consecutive patients with complete three-month data sets implanted with intrathecal pain pumps more than three years utilizing ziconotide as a first-line monotherapy...
August 5, 2016: Neuromodulation: Journal of the International Neuromodulation Society
Héléne Staquet, Denis Dupoiron, Edmond Nader, Philippe Menei
Intracerebroventricular (ICV) administration of opioids for control of intractable cancer pain has been used since 1982. We present here our experience of intracerebroventricular administration of pain treatments including ziconotide associated with morphine and ropivacaine for patients resistant to a conventional approach, with nociceptive, neuropathic, or mixed pain. These clinical cases were conducted with patients suffering from refractory pain, more than 6/10 on a numerical pain rating scale (NPRS) while on high-dose medical treatment and/or intolerance with significant side effects from oral medication...
July 2016: Pain Physician
John C O'Donnell, Joshua G Jackson, Michael B Robinson
UNLABELLED: Recently, mitochondria have been localized to astrocytic processes where they shape Ca(2+) signaling; this relationship has not been examined in models of ischemia/reperfusion. We biolistically transfected astrocytes in rat hippocampal slice cultures to facilitate fluorescent confocal microscopy, and subjected these slices to transient oxygen/glucose deprivation (OGD) that causes delayed excitotoxic death of CA1 pyramidal neurons. This insult caused a delayed loss of mitochondria from astrocytic processes and increased colocalization of mitochondria with the autophagosome marker LC3B...
July 6, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
J Gorson, M Holford
Venomous organisms used in research were historically chosen based on size and availability. This opportunity-driven strategy created a species bias in which snakes, scorpions, and spiders became the primary subjects of venom research. Increasing technological advancements have enabled interdisciplinary studies using genomics, transcriptomics, and proteomics to expand venom investigation to animals that produce small amounts of venom or lack traditional venom producing organs. One group of non-traditional venomous organisms that have benefitted from the rise of -omic technologies is the Conoideans...
July 1, 2016: Integrative and Comparative Biology
Brian M Bruel, Allen W Burton
OBJECTIVE: The increasing incidence of cancer survivorship has shifted treatment of cancer-related pain from short-term analgesia to long-term chronic pain management. As a result, alternatives to oral analgesics, such as intrathecal therapy, may be beneficial for patients with cancer-related pain. The authors review the use of intrathecal therapy in the management of cancer-related pain. METHODS: The Medline database was searched for English-language articles that included "ziconotide" or "morphine" AND ("cancer" OR "malignant") AND "intrathecal" in title or abstract...
April 28, 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Jason E Pope, Timothy R Deer, Brian M Bruel, Steven Falowski
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)...
February 23, 2016: Pain Practice: the Official Journal of World Institute of Pain
Morag E Brookes, Sam Eldabe, Alan Batterham
INTRODUCTION: Chronic neuropathic pain is difficult to treat and is often refractory to most modalities of treatment. Ziconotide is a novel, potent, non-opioid, calcium channel blocking agent which has been shown in clinical trials to be effective in treating chronic neuropathic pain. METHODS: EMBASE, MEDLINE, CINAHL Plus and Web of Science electronic databases were searched for English language studies. Reference sections of articles were examined for further papers and the manufacturer of ziconotide was contacted for further unpublished data...
February 10, 2016: Current Neuropharmacology
J E Pope, T R Deer, K Amirdelfan, W P McRoberts, N Azeem
Intrathecal drug delivery has undergone a revitalization following a better understanding of this delivery route and its pharmacokinetics. Driven by patient safety and outcomes, clinicians are motivated to rethink the traditional spinal infusion pump patient selection criteria and indications. We review the current understanding of the pharmacology of commonly employed intrathecal agents and the clinical relevance.
February 10, 2016: Current Neuropharmacology
Gladstone C McDowell, Jason E Pope
INTRODUCTION: Ziconotide is a non-opioid analgesic for intrathecal (IT) administration. The aim of this review is to provide a comprehensive and clinically relevant summary of the literature on dosing and administration with IT ziconotide in the management of refractory chronic pain, and to describe novel dosing strategies intended to improve clinical outcomes. MATERIALS AND METHODS: A Medline search was conducted for "ziconotide," supplemented by manual searching of published bibliographies and abstracts from conferences...
July 2016: Neuromodulation: Journal of the International Neuromodulation Society
Patrizia Russo, Aliaksei Kisialiou, Palma Lamonaca, Rossana Moroni, Giulia Prinzi, Massimo Fini
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder. Current approved drugs may only ameliorate symptoms in a restricted number of patients and for a restricted period of time. Currently, there is a translational research challenge into identifying the new effective drugs and their respective new therapeutic targets in AD and other neurodegenerative disorders. In this review, selected examples of marine-derived compounds in neurodegeneration, specifically in AD field are reported. The emphasis has been done on compounds and their possible relevant biological activities...
January 2016: Marine Drugs
Rosario Russo, Maria Cristina Caroleo, Erika Cione, Mariarita Perri, Maria Teresa Paparo, Antonio Russo
Erythromelalgia (EM) is a rare disabling clinical syndrome more commonly known to affect the lower extremities. There is no single effective treatment for this disease that often requires a multidisciplinary approach. Herein, we report the case of a 31-year-old woman affected by primary erythromelalgia who was successfully treated with intrathecal Ziconotide. We also observed an unexpected result following therapy with Ziconotide. The legs and feet of the patient that at the time of admission were swollen and tumefied dramatically improved after one week of the drug administration...
2015: Case Reports in Medicine
Ana Bella de la Calle Gil, Isaac Peña Vergara, María Auxiliadora Cormane Bornacelly, Antonio Pajuelo Gallego
INTRODUCTION: Studies have shown that, at low doses and with careful titration, combination therapy with intrathecal ziconotide and morphine results in rapid control of opioid-refractory cancer pain. However, there is a lack of published data regarding the efficacy and safety of intrathecal ziconotide specifically for the treatment of neuropathic cancer pain. CASE SERIES: Case reports of ziconotide intrathecal infusion in eight patients (age 45-71 years; 75% male) with chronic, uncontrolled cancer pain during therapy with intrathecal morphine plus bupivacaine were reviewed...
December 2015: Neurology and Therapy
Paul Farquhar-Smith, Suzanne Chapman
1. Neuraxial opioids are considered for use in patients who have resistant intractable pain that fails to respond to other treatment options or pain that responds to analgesia but for which the doses required result in unacceptable side-effects. 2. Neuraxial opiods can be considered for both chronic non-malignant pain and chronic cancer-related pain. 3. Effectiveness in chronic non-malignant pain and cancer pain is exerted through the use of either single-agent drugs (opioids) or a combination of drugs: opioids, local anaesthetics and other drugs such as clonodine and ziconotide...
February 2012: British Journal of Pain
Catherine Smyth, Nadera Ahmadzai, Jason Wentzell, Ashley Pardoe, Andrew Tse, Tiffany Nguyen, Yvette Goddard, Shona Nair, Patricia A Poulin, Becky Skidmore, Mohammed T Ansari
The intrathecal drug-delivery system (IDDS) is one mode of infusing analgesic medications directly into the cerebrospinal fluid in close proximity to their site of action. This modality has been employed in patients with refractory pain either due to malignant or non-malignant causes for over 30 years. Unfortunately, and despite the number of years it has been in use, there is still a scarcity of rigorous evidence to guide its integration into clinical practice. Current best evidence is inconclusive as to the comparative effectiveness and harms of the IDDS relative to routine medical care of patients...
November 2015: Drugs
Peter J Duggan, Kellie L Tuck
Ziconotide (Prialt®), a synthetic version of the peptide ω-conotoxin MVIIA found in the venom of a fish-hunting marine cone snail Conus magnus, is one of very few drugs effective in the treatment of intractable chronic pain. However, its intrathecal mode of delivery and narrow therapeutic window cause complications for patients. This review will summarize progress in the development of small molecule, non-peptidic mimics of Conotoxins and a small number of other venom peptides. This will include a description of how some of the initially designed mimics have been modified to improve their drug-like properties...
October 2015: Toxins
Sachin Narain, Lama Al-Khoury, Eric Chang
BACKGROUND: Migraine headaches are a common and functionally debilitating disorder affecting approximately 17% of women and 5.6% of men. Compared to episodic migraine patients, chronic migraineurs are more likely to be occupationally disabled, miss family activities, have comorbid anxiety and/or chronic pain disorders, and utilize significantly more health care dollars. Ziconotide is a calcium channel blocker used for the treatment of chronic severe pain without issues of tolerance or dependency found with opioid therapy...
2015: Journal of Pain Research
Gerald W Zamponi, Joerg Striessnig, Alexandra Koschak, Annette C Dolphin
Voltage-gated calcium channels are required for many key functions in the body. In this review, the different subtypes of voltage-gated calcium channels are described and their physiologic roles and pharmacology are outlined. We describe the current uses of drugs interacting with the different calcium channel subtypes and subunits, as well as specific areas in which there is strong potential for future drug development. Current therapeutic agents include drugs targeting L-type Ca(V)1.2 calcium channels, particularly 1,4-dihydropyridines, which are widely used in the treatment of hypertension...
October 2015: Pharmacological Reviews
Fei Wang, Zhenzhen Yan, Zhuguo Liu, Sheng Wang, Qiaoling Wu, Shuo Yu, Jiuping Ding, Qiuyun Dai
MVIIA (ziconotide) is a specific inhibitor of N-type calcium channel, Cav2.2. It is derived from Cone snail and currently used for the treatment of severe chronic pains in patients unresponsive to opioid therapy. However, MVIIA produces severe side-effects, including dizziness, nystagmus, somnolence, abnormal gait, and ataxia, that limit its wider application. We previously identified a novel inhibitor of Cav2.2, ω-conopeptide SO-3, which possesses similar structure and analgesic activity to MVIIA's. To investigate the key residues for MVIIA toxicity, MVIIA/SO-3 hybrids and MVIIA variants carrying mutations in its loop 2 were synthesized...
February 2016: Neuropharmacology
Prachi Anand, Alison O'Neil, Emily Lin, Trevor Douglas, Mandë Holford
The blood brain barrier (BBB) is often an insurmountable obstacle for a large number of candidate drugs, including peptides, antibiotics, and chemotherapeutic agents. Devising an adroit delivery method to cross the BBB is essential to unlocking widespread application of peptide therapeutics. Presented here is an engineered nanocontainer for delivering peptidic drugs across the BBB encapsulating the analgesic marine snail peptide ziconotide (Prialt®). We developed a bi-functional viral nanocontainer based on the Salmonella typhimurium bacteriophage P22 capsid, genetically incorporating ziconotide in the interior cavity, and chemically attaching cell penetrating HIV-Tat peptide on the exterior of the capsid...
2015: Scientific Reports
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