To evaluate the effectiveness and safety of a cancer pain information platform combined with semi-implantable intrathecal drug delivery systems among the patients with refractory cancer pain under a \"home analgesia\" model. This was a retrospective study. A total of 49 patients underwent semi-implantable intrathecal drug delivery systems with patient-controlled analgesia in conjunction with the establishment of a cancer pain information platform. Numeric rating scales (NRS), Bruggrmann comfort scale (BCS), high-quality sleep duration, and opioid-related adverse effects were recorded at various time points and analyzed: the day on admission (T0), the day of discharge (T1), 30 days post-discharge (T2), 60 days post-discharge (T3), 90 days post-discharge (T4), 120 days post-discharge (T5), 150 days post-discharge (T6), 180 days post-discharge (T7), and the day before death (T8). Compared with T0, NRS significantly decreased and BCS significantly increased at T1 to T8 time points (P < .05). However, NRS and BCS did not show differences at T1 to T8 time points (P > .05). The duration of high-quality sleep was significantly extended, and the incidence of opioid-related adverse effects was significantly reduced. Postoperative complications included 1 case of cerebrospinal fluid leakage, 3 cases of infection at the butterfly needle insertion site, 6 cases of hospital readmission for equipment malfunction, and no cases of respiratory depression. Eleven patients continued standardized antitreatment after IDDS surgery. The mean survival time for all patients was 135.51 ± 102.69 days, and the survival rate at T7 was 30.61%. The cancer pain information platform combined with semi-implantable IDDS is beneficial for the pain management of refractory cancer patients under the \"home analgesia\" model, improving their quality of life.

BACKGROUND: Dexamethasone palmitate (DEP), a prodrug of dexamethasone (DEX), is a synthetic corticosteroid medication distinguished by the inclusion of a fatty acid component known as palmitate. This study introduces DEP as a novel therapeutic option for spinal epidural injection, aiming to provide safer and longer-lasting pain relief as an alternative to for patients with spinal stenosis.
METHODS: 40 rats were randomly divided into four groups: those receiving epidural administration of normal saline (NS), and DEP in the lumbar spinal stenosis (LSS) model, and non-model rats receiving epidural NS administration. Paw withdrawal thresholds to mechanical stimulation and motor function (neurogenic intermittent claudication) were observed for up to 21 days. Hematology and blood chemistry analyses were performed 1 week after drug therapy. Tissue samples were collected for steroid pathology examination to evaluate adhesion degree, perineural area inflammation, and chromatolysis in the dorsal root ganglion (DRG), and adrenal gland.
RESULTS: The DEX and DEP groups demonstrated significant recovery from mechanical allodynia and motor dysfunction after 2 weeks of drug therapy (p<0.001). However, by the third week, the effect of DEX started to diminish while the effect of DEP persisted. Furthermore, the DEP group exhibited reduced fibrosis and less chromatolysis than the NS group. No steroid overdose or toxin was observed in any group.
CONCLUSIONS: The epidural administration of DEP demonstrated therapeutic efficacy in reducing allodynia and hyperalgesia resulting from chronic DRG compression, thus offering prolonged pain relief. These findings underscore the potential of DEP as a promising treatment alternative for pain associated with LSS, serving as a viable substitute for .

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Opioids are the gold standard for the treatment of chronic pain but are limited by adverse side effects. In our earlier work, we showed that Heat shock protein 90 (Hsp90) has a crucial role in regulating opioid signaling in spinal cord; Hsp90 inhibition in spinal cord enhances opioid anti-nociception. Building on these findings, we injected the non-selective Hsp90 inhibitor KU-32 by the intrathecal route into male and female CD-1 mice, showing that morphine anti-nociceptive potency was boosted by 1.9-3.5-fold in acute and chronic pain models. At the same time, tolerance was reduced from 21-fold to 2.9 fold and established tolerance was rescued, while the potency of constipation and reward was unchanged. These results demonstrate that spinal Hsp90 inhibition can improve the therapeutic index of morphine. However, we also found that systemic non-selective Hsp90 inhibition blocked opioid pain relief. To avoid this effect, we used selective small molecule inhibitors and CRISPR gene editing to identify 3 Hsp90 isoforms active in spinal cord (Hsp90α, Hsp90β, and Grp94) while only Hsp90α was active in brain. We thus hypothesized that a systemically delivered selective inhibitor to Hsp90β or Grp94 could selectively inhibit spinal cord Hsp90 activity, resulting in enhanced opioid therapy. We tested this hypothesis using intravenous delivery of KUNB106 (Hsp90β) and KUNG65 (Grp94), showing that both drugs enhanced morphine anti-nociceptive potency while rescuing tolerance. Together, these results suggest that selective inhibition of spinal cord Hsp90 isoforms is a novel, translationally feasible strategy to improve the therapeutic index of opioids.

This article describes a step-by-step process of lumbar intrathecal injection of Evans blue dye and AAV9-EGFP in adult (2-month-old) and neonatal (postnatal day 10) mice. Intrathecal injection is a clinically translatable technique that has already been extensively applied in humans. In mice, intrathecal injection is considered a challenging procedure that requires a trained and experienced researcher. For both adult and neonatal mice, lumbar intrathecal injection is directed into the L5-L6 intervertebral space. Intrathecally injected material enters the cerebrospinal fluid (CSF) within the intrathecal space from where it can directly access the central nervous system (CNS) parenchyma. Simultaneously, intrathecally injected material exits the CSF with pressure gradient and enters the endoneurial fluid and ultimately the peripheral nerves. While in the CSF, the injectable material also enters the bloodstream and systemic circulation through the arachnoid villi. A successful lumbar intrathecal injection results in adequate biodistribution of the injectable material in the CNS, PNS, and peripheral organs. When correctly applied, this technique is considered as minimally invasive and non-disruptive and can be used for the lumbar delivery of any solute. © 2024 Wiley Periodicals LLC. Basic Protocol 1: C57BL/6 adult and P10 mice lumbar intrathecal injection Basic Protocol 2: Tissue collection and preparation for evaluating Evans blue dye diffusion Basic Protocol 3: Tissue collection and preparation for immunohistochemistry staining Basic Protocol 4: Tissue collection and vector genome copy number analysis.

BACKGROUND: Complex spinal deformities necessitate surgical interventions that may intervene with intrathecal injections in patients with spinal muscular atrophy (SMA). This study aimed to determine the effect of spinal deformity correction surgery on nusinersen administration.
METHODS: Pediatric patients with SMA, operated by a single surgeon, either via magnetically controlled growing rod (MCGR) or definitive fusion (DF) with skip instrumentation, were evaluated retrospectively in terms of safety and feasibility of intrathecal injections. Patients\' and their parents\' perspectives were evaluated through a questionnaire regarding any shift in the setting of injections.
RESULTS: Fourteen patients with 15 spinal surgeries (10 MCGR and 5 DF) were included. Eleven patients received intrathecal treatment both before and after the surgery. Preoperative (n=3) and postoperative (n=9) fluoroscopic guidance was required leading to a shift in the application settings in 6 patients. Of 106 preoperative injections, 15% required fluoroscopy and 2% required anesthesia. Postoperatively, of 88 injections, 73% required fluoroscopy and 26% required anesthesia. No patients discontinued intrathecal injections due to technical difficulties associated with the spinal surgery.
CONCLUSIONS: This study demonstrates that spinal surgery does not prevent safe and successful intrathecal nusinersen injections. In the DF group, the skip instrumentation technique provided access to interlaminal space for intrathecal injections. In either surgical group, no further auxillary approach was required. Modifications in the injection technique require an institutional approach, and concerns of patients and their families should be addressed accordingly.
METHODS: IV.

Treating metastatic malignancies to the central nervous system (CNS) is challenging because many drugs cannot cross the blood-brain-barrier (BBB). Direct intrathecal (IT) drug administration into the cerebrospinal fluid (CSF) is a strategy to overcome this problem. Thiotepa has effective CNS penetration but its popularity has waned over the last two decades due to concerns about its efficacy and potential systemic toxicity. This review evaluates the available evidence for the use of IT thiotepa in hematologic malignancies and non-CNS solid tumors with leptomeningeal disease metastases (LMD). Our search shows that IT thiotepa is a reasonable alternative in hematologic malignancies and LMD due to solid organ malignancies. This suggests a potential role of IT thiotepa in second-or third-line treatment or a substitute role in cases of drug-shortages and adverse effects with other agents. Future research should focus on rigorous comparative trials to establish its definitive role in the evolving landscape of CNS-directed chemotherapy.

BACKGROUND: The first pump for intrathecal administration of baclofen was implanted in 1984. Over thirty years, intrathecal prolonged infusion of muscle relaxants has occupied a worthy niche among all methods for correction of non-focal drug-resistant disabling muscle spasticity. However, this method has not become routine despite high awareness of specialists in Russia and abroad, as well as undeniable advantages for restoring the daily activity, improving the walking pattern and providing care and quality of life in people with limited mobility. This is due to scrupulous analysis of adverse events and accurate attitude towards its use.
The purpose of this review was to systematize data on indications, selection criteria, pump implantation technique, subsequent patient management and treatment outcomes over a 30-year history.
METHODS: A review of national and foreign literature was performed.
CONCLUSIONS: Prolonged intrathecal baclofen therapy is perspective for long-term treatment of severe spasticity interfering with quality of life and self-care if oral muscle relaxants are contraindicated or ineffective. This procedure is effective for impaired articulation, chewing and spastic pain syndrome. One can reduce the incidence of side effects via correct dosage of the drug, and tolerance to therapy can be reduced by timely elimination of problems with catheter.
Начавшись с первой имплантированной помпы для интратекального введения баклофена в 1984 г., за 30 лет использования метод интратекальной пролонгированной инфузии миорелаксантов занял достойную нишу среди способов коррекции нефокальной резистентной инвалидизирующей мышечной спастичности. Однако метод не стал рутинным, несмотря на высокую информированность специалистов как в России, так и за рубежом, и неоспоримые преимущества для восстановления повседневной активности и улучшения стереотипа ходьбы у пациентов с высоким уровнем функциональных возможностей, а также для обеспечения ухода и качества жизни маломобильных больных, что обусловлено скрупулезным анализом нежелательных явлений и взвешенным отношением к его использованию.
UNASSIGNED: Систематизация информации по показаниям, критериям отбора на операцию, технике проведения имплантации помпы, последующему ведению пациентов и результатам лечения за 30-летний период применения метода.
UNASSIGNED: Выполнен повествовательный обзор отечественной и зарубежной литературы.
UNASSIGNED: Изучение источников литературы позволяет сделать вывод о перспективности пролонгированного интратекального введения баклофена в долгосрочной терапии выраженной спастичности, нарушающей качество жизни и самообслуживание, при непереносимости или неэффективности пероральных миорелаксантов. Процедура эффективна при нарушении артикуляции, жевания, спастическом болевом синдроме. Частоту побочных эффектов можно снизить за счет корректной дозировки препарата, а толерантность к терапии — своевременным устранением проблем с катетером.

Leptomeningeal metastases are lesions of brain and/or spinal cord sheaths by tumor cells. They occur in 5% of patients with solid tumors, although autopsies reveal these lesions much more often (10-20% of cases). Leptomengeal metastases are an unfavorable prognostic factor. Despite the modern NCCN treatment standards, including intrathecal therapy (ITT), such patients receive only irradiation of the entire brain and/or spinal cord in most cases.
OBJECTIVE: To evaluate the effectiveness of ITT in patients with leptomeningeal metastases in breast cancer.
METHODS: Twenty-five patients with breast cancer and leptomeningeal metastases underwent intrathecal administration of methotrexate between 2016 and 2022. Intrathecal chemotherapy was administered through lumbar puncture. We performed an intensive course (intrathecal methotrexate 15 mg 2 times a week for 1 month (8 injections), then intrathecal methotrexate 15 mg 1 time a week (4 injections), and then 15 mg 1 time a month until progression or unacceptable toxicity).
RESULTS: The median duration of ITT was 2.5 months. Complete neurological responses were observed in 3 out of 25 (12%) patients, partial neurological response - in 15 out of 25 (60%) patients, progression of neurological symptoms - in 7 (28%) patients. The number of complete cytological responses was observed in 6 out of 25 (24%) patients. The median overall survival after ITT was 6.7 months.
CONCLUSIONS: Effectiveness of ITT is confirmed by higher quality of life (72% of patients), complete cytological responses (24%) and improvement in neuroimaging data. This is an important criterion for severe patients with limited treatment options. First-stage ITT before whole-brain irradiation is preferable, as this approach increases overall survival by 3 months. Undoubtedly, ITT is a treatment option that can be used in routine clinical practice for lesions of brain and spinal cord sheaths.
Лептоменингеальные метастазы — поражение опухолевыми клетками оболочек головного и/или спинного мозга. Развиваются у 5% больных с солидными опухолями, хотя на аутопсиях поражение оболочек выявляется значительно чаще — в 10—20% случаев. Лептоменингеальные метастазы считаются неблагоприятным фактором прогноза. Несмотря на имеющиеся стандарты лечения, по данным Национальной комплексной онкологической сети (National Comprehensive Cancer Network, NCCN), включающие интратекальную терапию (ИТТ), таким пациенткам в большинстве случаев проводится только облучение всего головного и/или спинного мозга.
UNASSIGNED: Оценка эффективности ИТТ у больных с лептоменингеальными метастазами при раке молочных желез (РМЖ).
UNASSIGNED: В отделении нейроонкологии ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России в период с 2016 по 2022 г. интратекальное введение метотрексата получили 25 больных РМЖ с лептоменингеальными метастазами. ИТТ-химиотерапия проводилась посредством люмбальной пункции. Интенсивный курс в дозе 15 мг метотрексата интратекально 2 раза в неделю в течение 1 мес (8 введений), далее по 15 мг метотрексата интратекально 1 раз в неделю (4 введения), далее по 15 мг 1 раз в месяц до прогрессирования или неприемлемой токсичности.
UNASSIGNED: Медиана длительности проводимой ИТТ составила 2,5 мес. Количество полных неврологических ответов отмечено у 3 (12%) из 25 пациенток. Частичный неврологический ответ — у 15 (60%) из 25 больных, у 7 (28%) пациенток отмечалось прогрессирование неврологической симптоматики. Количество полных цитологических ответов наблюдалось у 6 (24%) из 25 больных. Медиана общей выживаемости больных, получивших ИТТ, составила 6,7 мес.
UNASSIGNED: Эффективность лечения ИТТ подтверждена улучшением качества жизни больных (72%), полными цитологическими ответами (24%) и улучшением картины при нейровизуализации, что является немаловажным критерием для тяжелой категории больных с ограниченными лечебными опциями. Предпочтительнее проводить ИТТ на первом этапе лечения, до облучения всего головного мозга, поскольку это увеличивает медиану общей выживаемости на 3 мес. Несомненно, проведение ИТТ — это лечебная опция, которая может использоваться в рутинной клинической практике при поражении оболочек головного и спинного мозга.