Ziconotide for treatment of severe chronic pain

Schmidtko, Achim; Lötsch, Jörn; Freynhagen, Rainer; Geißlinger, Gerd

doi:10.1016/s0140-6736(10)60354-6

Cited by 312 publications

(260 citation statements)

References 61 publications

Supporting

Mentioning

247

Contrasting

Unclassified

Order By: Relevance

“…Consistent with the role of CaV2.2 in pain signaling, genetic deletion, as well as pharmacologic block of CaV2.2, impairs nociceptive processing (3,54). Additionally, central blockade of CaV2.2 is effective in treating some cases of chronic pain that have been intractable to other interventions (8).…”

Section: Discussionmentioning

confidence: 77%

“…Indeed, inhibition of CaV2.2 by synthetic conopeptides provides analgesic relief in a variety of platforms (3)(4)(5)(6). However, given the importance of CaV2.2 integrity in peripheral and central synapses, directly targeting channel function is complicated by a myriad of adverse side effects (7)(8)(9). Targeting protein-protein interactions that regulate CaV2.2 may provide analgesic benefits similar to those provided by direct inhibition, while avoiding complications associated with channel block.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of Transmitter Release and Attenuation of Anti-retroviral-associated and Tibial Nerve Injury-related Painful Peripheral Neuropathy by Novel Synthetic Ca2+ Channel Peptides

Wilson

Schmutzler

Brittain

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: N-type Ca 2ϩ channels (CaV2.2) are clinically validated targets for chronic pain. Results: Two peptides from CaV2.2 and CaV1.2 perturb binding to a regulatory protein, CRMP2, inhibit calcium influx, and attenuate mechanical hyperalgesia in a rodent model of drug-induced chronic pain. Conclusion: Ca 2ϩ channel peptides block drug-and nerve injury-induced chronic pain. Significance: Ca 2ϩ channel peptide therapeutics can be useful in mitigating chronic pain.

show abstract

Section: Discussionmentioning

confidence: 77%

mentioning

confidence: 99%

Inhibition of Transmitter Release and Attenuation of Anti-retroviral-associated and Tibial Nerve Injury-related Painful Peripheral Neuropathy by Novel Synthetic Ca2+ Channel Peptides

Wilson

Schmutzler

Brittain

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Typical opioid adverse events (AEs) such as respiratory depression, tolerance or dependence have not been described for ziconotide [215]. However, ziconotide has a narrow therapeutic window [189,215] and several neurological AEs have been reported, e.g.…”

Section: Ziconotidementioning

confidence: 99%

“…Before each ziconotide injection, a blood sample for Creatine Kinase (CK) was taken [215]. Commercially available ziconotide (Prialt®) was used.…”

Section: Ziconotide Trialing Proceduresmentioning

confidence: 99%

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

Bäckryd¹

2015

View full text Add to dashboard Cite

The treatment of both cancer pain and non-cancer chronic pain is still suboptimal. The overall aim of this PhD thesis was to conduct translational pain research at the interface between clinical pain medicine and the field of human proteomics, using the practice of intrathecal analgesia at our institution as a starting point. Hence, the cerebrospinal fluid (CSF) is at the centre of the present dissertation, both as a target for infusing analgesics (Papers I and II – clinical and pharmacological aspects) and as an important biofluid for human biomarker studies (Papers III and IV – proteomic aspects). In Paper I, 28 cases of intrathecal analgesia in cancer patients were prospectively followed. Movement-evoked breakthrough pain remained a major clinical problem throughout the study month despite otherwise successful intrathecal analgesia (defined as good control of spontaneous resting pain paralleled by a marked decrease of concomitant systemic opioid doses). This study therefore illustrates the importance of considering not only spontaneous resting pain but also movement-evoked breakthrough pain. In Paper II, an expert-based algorithm for trialing the intrathecal analgesic ziconotide by bolus injections was evaluated in an open-label study of 23 patients with chronic neuropathic pain. We found few responders (13%) according to the strict criteria of the algorithm, but ziconotide bolus injection trialing seems feasible. The predictive power of ziconotide bolus trialing remains unclear, and the pharmacological profile of ziconotide (with very slow tissue penetration due to high hydrophilicity) calls the rationale for ziconotide bolus trialing into question. In Paper III, we found low levels of beta-endorphin in the CSF of chronic neuropathic pain patients (n=15) compared to healthy controls (n=19). We speculate that this might indicate dysfunctional top-down control of nociception. Substance P levels in the CSF did not differ by univariate statistics. In Paper IV, the CSF proteome of 11 patients with chronic neuropathic pain and 11 healthy controls was exploratively studied, combining gel-based proteomics with multivariate data analysis. After eliminating four proteins associated with age, 32 proteins were found to highly discriminate between groups. Among these, the seven proteins having the highest discriminatory power between patients and controls were: one isoform of angiotensinogen, two isoforms of alpha-1-antitrypsin, three isoforms of haptoglobin, and one isoform of pigment epithelium-derived factor. In conclusion, this PhD thesis demonstrates the fruitfulness of studying the CSF, both as a target for infusing analgesics and as a potential mirror of the neurobiological processes involved in pathological pain conditions. The thesis points to the need for more research into the mechanisms of different pain conditions, in order to hopefully achieve the vision of mechanism-based pain diagnoses

show abstract

“…Ropivacaïne or bupivacaine are used to strengthen morphine effects by blocking nerve conduction in the sodium channels. Ziconotide is a small ω-conotoxine peptide isolated from a marine cone snail, Conus magus and acts as a selective blocker of voltage-sensitive calcium channels of N-type [8][9][10][11]. Due to its narrow therapeutic range and its potentially serious adverse effects (psychiatric and nervous system disorders), this drug is only indicated for the treatment of severe, chronic pain in adults who require intrathecal (IT) analgesia [12,13].…”

Section: Introductionmentioning

confidence: 99%

Validation Study of UPLC Method for Determination of Morphine, Ropivacaïne and Ziconotide in Combination for Intrathecal Analgesia

Rossignol¹,

Sorrieul²,

Beaussart³

et al. 2016

J Anal Bioanal Tech

View full text Add to dashboard Cite

Pain is often considered as the most feared symptom amongst individuals living with cancer. It can arrive at any stage during the course of the illness. In 15% to 20% of patients, conventional analgesic therapy either fails to relieve pain or induces adverse effects. Use of analgesic admixture has been recommended by the most recent consensus conferences. Several studies found evidence of synergistic effects of intrathecal analgesic admixtures, most notably these containing ziconotide, morphine and ropivacaïne, administering by a fully implantable pumps. The refills were prepared under a laminar airflow hood under strictly aseptic conditions, by the hospital pharmacist. This group of

show abstract

Ziconotide for treatment of severe chronic pain

Cited by 312 publications

References 61 publications

Inhibition of Transmitter Release and Attenuation of Anti-retroviral-associated and Tibial Nerve Injury-related Painful Peripheral Neuropathy by Novel Synthetic Ca2+ Channel Peptides

Inhibition of Transmitter Release and Attenuation of Anti-retroviral-associated and Tibial Nerve Injury-related Painful Peripheral Neuropathy by Novel Synthetic Ca2+ Channel Peptides

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

Validation Study of UPLC Method for Determination of Morphine, Ropivacaïne and Ziconotide in Combination for Intrathecal Analgesia

Contact Info

Product

Resources

About