Programmable intrathecal pumps for the management of chronic pain: recommendations for improved efficiency

Wilkes, Denise

doi:10.2147/jpr.s46929

Cited by 35 publications

(23 citation statements)

References 42 publications

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“…Oligonucleotide delivery using osmotic pumps is a recognized technique with potential therapeutic applications in mammals including humans. 45 , 46 , 47 , 48 We therefore used this strategy to deliver miR-16 mimics into the mouse brain. We chose wild-type mice—instead of AD mice—for these in vivo preclinical studies since harboring all physiological regulatory elements ( e.g.…”

Section: Resultsmentioning

confidence: 99%

Preclinical Evaluation of miR-15/107 Family Members as Multifactorial Drug Targets for Alzheimer's Disease

Parsi

Smith

Goupil

et al. 2015

Molecular Therapy - Nucleic Acids

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Alzheimer's disease (AD) is a multifactorial, fatal neurodegenerative disorder characterized by the abnormal accumulation of Aβ and Tau deposits in the brain. There is no cure for AD, and failure at different clinical trials emphasizes the need for new treatments. In recent years, significant progress has been made toward the development of miRNA-based therapeutics for human disorders. This study was designed to evaluate the efficiency and potential safety of miRNA replacement therapy in AD, using miR-15/107 paralogues as candidate drug targets. We identified miR-16 as a potent inhibitor of amyloid precursor protein (APP) and BACE1 expression, Aβ peptide production, and Tau phosphorylation in cells. Brain delivery of miR-16 mimics in mice resulted in a reduction of AD-related genes APP, BACE1, and Tau in a region-dependent manner. We further identified Nicastrin, a γ-secretase component involved in Aβ generation, as a target of miR-16. Proteomics analysis identified a number of additional putative miR-16 targets in vivo, including α-Synuclein and Transferrin receptor 1. Top-ranking biological networks associated with miR-16 delivery included AD and oxidative stress. Collectively, our data suggest that miR-16 is a good candidate for future drug development by targeting simultaneously endogenous regulators of AD biomarkers (i.e., Aβ and Tau), inflammation, and oxidative stress.

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Section: Resultsmentioning

confidence: 99%

Preclinical Evaluation of miR-15/107 Family Members as Multifactorial Drug Targets for Alzheimer's Disease

Parsi

Smith

Goupil

et al. 2015

Molecular Therapy - Nucleic Acids

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“…Breakthrough pain in patients managed with an intrathecal delivery system historically required additional oral pain medication, which necessitated a physician office visit. The versatility of TDD hardware and software has evolved from devices capable of simple continuous nonprogrammable flow, to TDD systems with time and daily‐programmable variable modes . Optimizing programming algorithms received attention after physicians treating spasticity demonstrated that baclofen tolerance can be reversed when the agent is administered by daily timed bolus rather than continuous infusion .…”

Section: Introductionmentioning

confidence: 99%

Efficacy of a Targeted Drug Delivery on‐Demand Bolus Option for Chronic Pain

et al. 2017

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“…[ 31 ] Successful clinical implementation of the implantable pump requires significant training of the physicians. [ 32 ] Additionally, the implantable pumps are not cost-effective in patients with short life expectancy. [ 10 ] An external drug infusion is used as an alternative approach in cancer patients with a short life expectancy.…”

Section: Discussionmentioning

confidence: 99%

Palliative care with cervical intrathecal infusion and external pump for a late-stage cancer patient with refractory pain

Tian

Tan

et al. 2018

Medicine

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Rationale:Intrathecal therapy, with a low complication rate, has become an alternative to standard pain management for treatment of neuropathic cancer pain.Patient concerns:Here, we reported a late-stage cancer patient with intractable neuropathic pain in his right neck, shoulder, and upper limb.Diagnoses:The pain started 2 years ago when the patient was diagnosed as squamous cell carcinoma with metastasis to right supraclavicular lymph nodes.Interventions:Cervical intrathecal infusion of morphine and bupivacaine with patient control analgesia by external pump was performed. The intrathecal catheter was located at the level of C6 vertebra. The initial concentration of bupivacaine and morphine were both 1 mg/mL with infusion rate of 0.3 mL/h and bolus of 0.3 mL. Subsequently, the concentrations increased to 2 mg/mL (bupivacaine) and 1.33 mg/mL (morphine), with infusion rate to 0.6 mL/h and bolus to 0.5 ml.Outcomes:The pain intensity decreased from numerical rating scale 6 to 7 to 2 to 3 at rest, and from 10 to 5 to 6 of breakthrough pain.Lessons:In conclusion, cervical intrathecal infusion requires low concentration but high doses of bupivacaine and morphine, which is safe and effective in cancer patients with refractory pain and short life expectancy.

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Programmable intrathecal pumps for the management of chronic pain: recommendations for improved efficiency

Cited by 35 publications

References 42 publications

Preclinical Evaluation of miR-15/107 Family Members as Multifactorial Drug Targets for Alzheimer's Disease

Preclinical Evaluation of miR-15/107 Family Members as Multifactorial Drug Targets for Alzheimer's Disease

Efficacy of a Targeted Drug Delivery on‐Demand Bolus Option for Chronic Pain

Palliative care with cervical intrathecal infusion and external pump for a late-stage cancer patient with refractory pain

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