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Ziconotide Trialing by Intrathecal Bolus Injections: An Open-Label Non-Randomized Clinical Trial in Postoperative/Posttraumatic Neuropathic Pain Patients Refractory to Conventional Treatment
Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin.ORCID-id: 0000-0003-4420-418X
Linköpings universitet, Institutionen för medicin och hälsa. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum. Linköpings universitet, Medicinska fakulteten.
Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum.
2015 (Engelska)Ingår i: Neuromodulation (Malden, Mass.), ISSN 1094-7159, E-ISSN 1525-1403, Vol. 18, nr 5, s. 404-413Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objectives: The aim of this open-label, non-randomized, clinical trial was to evaluate the feasibility of trialing ziconotide by intrathecal bolus injections. Material and Methods: Twenty-three patients, who had peripheral neuropathic pain refractory to pharmacological treatment and were under consideration for Spinal Cord Stimulation, received up to three ziconotide bolus injections according to a comprehensive algorithm. After a first injection of 2.5g, the patients progressed in the algorithm depending on the presence or absence of pain reduction and significant adverse events. A patient was considered a "responder" if experiencing pain reduction and no significant adverse event on two consecutive occasions at the same dosage. Results: We found a low proportion of responders (13%). However 30% of patients experienced greater than= 30% pain reduction on a least one injection, yielding a number needed to treat of similar to 3 for clinically significant pain relief. Pain intensity changed significantly over time (0-6h) (p = 0.047) after a mean ziconotide dose of 2.75 mu g. Adverse events were as expected, and no serious adverse event occurred. We did not find any statistical association between response to Spinal Cord Stimulation and response to ziconotide. Conclusions: Ziconotide bolus injection trialing seems feasible, but the proportion of responders in the present study was low. Adverse events were as expected, and no serious adverse event occurred. The predictive power of ziconotide bolus trialing remains unclear, and the pharmacological profile of ziconotide (slow tissue penetration due to high hydrophilicity) calls the rationale for bolus trialing into question.

Ort, förlag, år, upplaga, sidor
Wiley , 2015. Vol. 18, nr 5, s. 404-413
Nyckelord [en]
Bolus; intrathecal; spinal; trialing; ziconotide
Nationell ämneskategori
Klinisk medicin Medicinska och farmaceutiska grundvetenskaper
Identifikatorer
URN: urn:nbn:se:liu:diva-120352DOI: 10.1111/ner.12293ISI: 000357388400010PubMedID: 25879804OAI: oai:DiVA.org:liu-120352DiVA, id: diva2:843880
Anmärkning

Funding Agencies|County Council of Ostergotland; Swedish Research Council

Tillgänglig från: 2015-07-31 Skapad: 2015-07-31 Senast uppdaterad: 2018-01-11
Ingår i avhandling
1. The Cerebrospinal Fluid in Severe Pain Conditions: Clinical, Pharmacological and Proteomic Aspects
Öppna denna publikation i ny flik eller fönster >>The Cerebrospinal Fluid in Severe Pain Conditions: Clinical, Pharmacological and Proteomic Aspects
2015 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping University Electronic Press, 2015. s. 94
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1465
Nationell ämneskategori
Anestesi och intensivvård Neurovetenskaper
Identifikatorer
urn:nbn:se:liu:diva-121494 (URN)10.3384/diss.diva-121494 (DOI)978-91-7519-032-7 (ISBN)
Disputation
2015-11-13, Berzeliussalen, Ingång 65, Campus US, Linköping, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2015-09-22 Skapad: 2015-09-22 Senast uppdaterad: 2018-01-11Bibliografiskt granskad

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