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      Near-resolution of persistent idiopathic facial pain with low-dose lumbar intrathecal ziconotide: a case report

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          Persistent idiopathic facial pain (PIFP) is a poorly defined and debilitating chronic pain state with a challenging and often inadequate treatment course. This is the first case report identifying the novel use of low-dose lumbar intrathecal ziconotide to successfully treat PIFP with nearly complete resolution of pain and minimal to no side effects.


          The patient was a 37 year-old female whose PIFP was refractory to multimodal medication management and multiple neurovascular surgical interventions. A single-shot lumbar intrathecal trial of ziconotide (2.5 mL, equivalent 2.5 μg) was injected when she was at her baseline pain level — VAS 7/10. She received complete resolution of her pain for about 9 hours, concordant with ziconotide’s half-life. She was subsequently implanted with a lumbar intrathecal delivery system.


          The patient experienced complete resolution of her facial pain with a single-shot intrathecal trial of ziconotide. The intrathecal pump system has provided nearly complete (VAS 1/10) pain relief. Two flares of pain occurred 10 and 18 months after pump placement, which subsequently resolved after increasing the ziconotide dose by 0.5 μg/day on each occasion. The patient is currently maintained on a dose of 2.0 μg/day and is pain-free.


          This is the first case report describing the use of a single-shot lumbar intrathecal trial of ziconotide and subsequent placement of lumbar (as opposed to thoracic) intrathecal ziconotide pump for PIFP. A single-injection intrathecal trial is a low-risk, viable option for patients with this debilitating and frustrating pain condition. Successful trials and subsequent intrathecal pump placement with ziconotide may supplant multimodal medication management and/or invasive orofacial surgical intervention for PIFP.

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          Most cited references 31

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          Ziconotide: neuronal calcium channel blocker for treating severe chronic pain.

           G. Miljanich (2004)
          Ziconotide (PRIALT) is a neuroactive peptide in the final stages of clinical development as a novel non-opioid treatment for severe chronic pain. It is the synthetic equivalent of omega-MVIIA, a component of the venom of the marine snail, Conus magus. The mechanism of action underlying ziconotide's therapeutic profile derives from its potent and selective blockade of neuronal N-type voltage-sensitive calcium channels (N-VSCCs). Direct blockade of N-VSCCs inhibits the activity of a subset of neurons, including pain-sensing primary nociceptors. This mechanism of action distinguishes ziconotide from all other analgesics, including opioid analgesics. In fact, ziconotide is potently anti-nociceptive in animal models of pain in which morphine exhibits poor anti-nociceptive activity. Moreover, in contrast to opiates, tolerance to ziconotide is not observed. Clinical studies of ziconotide in more than 2,000 patients reveal important correlations to ziconotide's non-clinical pharmacology. For example, ziconotide provides significant pain relief to severe chronic pain sufferers who have failed to obtain relief from opiate therapy and no evidence of tolerance to ziconotide is seen in these patients. Contingent on regulatory approval, ziconotide will be the first in a new class of neurological drugs: the N-type calcium channel blockers, or NCCBs. Its novel mechanism of action as a non-opioid analgesic suggests ziconotide has the potential to play a valuable role in treatment regimens for severe chronic pain. If approved for clinical use, ziconotide will further validate the neuroactive venom peptides as a source of new and useful medicines.
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            Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial.

            Ziconotide (formerly SNX-111) selectively blocks N-type voltage-sensitive calcium channels and may be effective in patients with pain that is refractory to opioid therapy or those with intolerable opioid-related adverse effects. To assess the safety and efficacy of intrathecal ziconotide in patients with pain that is refractory to conventional treatment. Double-blind, placebo-controlled, randomized trial conducted from March 12, 1996, to July 11, 1998, at 32 study centers in the United States, Australia, and the Netherlands. Patients were 111 individuals ages 24 to 85 years with cancer or AIDS and a mean Visual Analog Scale of Pain Intensity (VASPI) score of 50 mm or greater. Patients were randomly assigned in a 2:1 ratio to receive ziconotide or placebo treatment. Intrathecal ziconotide was titrated over 5 to 6 days, followed by a 5-day maintenance phase for responders and crossover of nonresponders to the opposite treatment group. Mean percentage change in VASPI score from baseline to the end of the initial titration period. Of the evaluable population, 67 (98.5%) of 68 patients receiving ziconotide and 38 (95%) of 40 patients receiving placebo were taking opioids at baseline (median morphine equivalent dosage of 300 mg/d for the ziconotide group and 600 mg/d for the placebo group; P =.63, based on mean values), and 36 had used intrathecal morphine. Mean (SD) VASPI scores were 73.6 (1.8) mm in the ziconotide group and 77.9 (2.3) mm in the placebo group (P =.18). Mean VASPI scores improved 53.1% (95% confidence interval [CI], 44.0%-62.2%) in the ziconotide group and 18.1% (95% CI, 4.8%-31.4%) in the placebo group (P<.001), with no loss of efficacy of ziconotide in the maintenance phase. Pain relief was moderate to complete in 52.9% of patients in the ziconotide group compared with 17.5% in the placebo group (P<.001). Five patients receiving ziconotide achieved complete pain relief, and 50.0% of patients receiving ziconotide responded to therapy compared with 17.5% of those receiving placebo (P =.001). Intrathecal ziconotide provided clinically and statistically significant analgesia in patients with pain from cancer or AIDS.
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              Incidence of facial pain in the general population.

              Facial pain has a considerable impact on quality of life. Accurate incidence estimates in the general population are scant. The aim was therefore to estimate the incidence rate (IR) of trigeminal neuralgia (TGN), postherpetic neuralgia (PHN), cluster headache (CH), occipital neuralgia (ON), local neuralgia (LoN), atypical facial pain (AFP), glossopharyngeal neuralgia (GPN) and paroxysmal hemicrania (PH) in the Netherlands. In the population-based Integrated Primary Care Information (IPCI) medical record database potential facial pain cases were identified from codes and narratives. Two medical doctors reviewed medical records, questionnaires from general practitioners and specialist letters using criteria of the International Association for the Study of Pain. A pain specialist arbitrated if necessary and a random sample of all cases was evaluated by a neurologist. The date of onset was defined as date of first specific symptoms. The IR was calculated per 100,000PY. Three hundred and sixty-two incident cases were ascertained. The overall IR [95% confidence interval] was 38.7 [34.9-42.9]. It was more common among women compared to men. Trigeminal neuralgia and cluster headache were the most common forms among the studied diseases. Paroxysmal hemicrania and glossopharyngeal neuralgia were among the rarer syndromes. The IR increased with age for all diseases except CH and ON, peaking in the 4th and 7th decade, respectively. Postherpetic neuralgia, CH and LoN were more common in men than women. From this we can conclude that facial pain is relatively rare, although more common than estimated previously based on hospital data.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                08 March 2019
                : 12
                : 945-949
                [1 ]Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
                [2 ]Pain Management, Parkview Health, Fort Wayne, IN, USA
                [3 ]Department of Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
                [4 ]University of Pittsburgh Physicians, Pittsburgh, PA, USA, emericktd@ 123456upmc.edu
                [5 ]Division of Chronic Pain, Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, emericktd@ 123456upmc.edu
                Author notes
                Correspondence: Trent D Emerick, Division of Chronic Pain, Department of Anesthesiology, University of Pittsburgh School of Medicine, UPMC Montefiore Hospital, 3459 Fifth Avenue, Suite NE 570, Pittsburgh, PA 15213, USA, Tel +1 412 692 2234, Fax +1 412 692 2235, Email emericktd@ 123456upmc.edu
                © 2019 Staub et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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