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intracerebroventricular opiate infusion for refractory head and facial pain

World Journal of Clinical Cases 2014年第8期2卷 351-356页

作者： Darrin J Lee Gene G Gurkoff Amir Goodarzi J Paul Muizelaar James E Boggan Kiarash Shahlaie Department of Neurological Surgery School of MedicineUniversity of CaliforniaDavisCA 95817United States

AIM: To study the risks and benefits of intracerebroventricular(ICV) opiate pumps for the management of benign head and face ***: SSix patients with refractory trigeminal neuralgia and/or cluster headaches were evaluated for implantation of an ICV opiate infusion pump using either ICV injections through an Ommaya reservoir or external ventricular drain. Four patients received morphine ICV pumps and two patient S received a hydromorphone pump. Of the Four patients with morphine ICV pumps, one patient had the medication changed to hydromorphone. Preoperative and post-operative visual analog scores(VAS) were obtained. Patients were evaluated post-operatively for a minimum of 3 mo and the pump dosage was adjusted at each outpatient clinic visit according to the patient's pain ***: All 6 patients had an intracerebroventricular opiate injection trial period, using either an Ommaya reservoir or an external ventricular drain. There was an average VAS improvement of 75.8%. During the trial period, no complications were observed. Pump implantation was performed an average of 3.7 wk(range 1-7) after the trial injections. After implantation, an average of 20.7 ± 8.3 dose adjustments were made over 3-56 mo after surgery to achieve maximal pain relief. At the most recent follow-up(26.2 mo, range 3-56), VAS scores significantly improved from an average of 7.8 ± 0.5(range 6-10) to 2.8 ± 0.7(range 0-5) at the final dose(mean improvement 5.0 ± 1.0, P < 0.001). All patients required a stepwise increase in opiate infusion rates to achieve maximal benefit. The most common complications were nausea and drowsiness, both of which resolved with pump adjustments. On average, infusion pumps were replaced every 4-5 ***: These results suggest that ICV delivery of opiates may potentially be a viable treatment option for patients with intractable pain from trigeminal neuralgia or cluster headache.

关键词： intracerebroventricular Opiate Trigeminal neuralgia Cluster headache Pain

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The molecular regulatory effect of intracerebroventricular thymulin on endotoxin-mediated NF-<i>k</i>B nuclear translocation and activation <i>in vivo</i>

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American Journal of Molecular Biology 2013年第1期3卷 45-58页

作者： John J. Haddad Cellular and Molecular Physiology and Immunology Signaling Research Group Biomedical Laboratory and Clinical Sciences Division Department of Medical Laboratory Technology Faculty of Health Sciences Beirut Arab University Beirut Lebanon

The nuclear factor-kB (NF-kB) is one member of a ubiquitously expressed family of Rel-related transcription factors that serve as critical regulators of proinflammatory genes. The immunomodulatory potential of thymulin and its effect on NF-kB in vivo, particularly in the central nervous system (CNS), is not well characterized. In this study, the role of endotoxin (ET) in regulating NF-kB was unraveled in various compartments of the CNS. Stereotaxic localization reverberated specific intracerebroventricular (ICV) injection of ET into the CNS, with or without pretreatment with ICV thymulin. Treatment with ET upregulated the expression and nuclear trans-localization of NF-kB1 (p50), NF-kB2 (p52), RelA (p65), RelB (p68) and c-Rel (p75) in the hippocampus (HC), an effect abrogated by ICV pretreatment with thymulin. Thymulin modulated the phosphorylation of IkB-a in the HC by upregulating the cytosolic accumulation of IkB-a and downregulating its phosphorylation (pIkB-a). Further analysis of the DNA-binding activity revealed an upregulated activity in the HC relative to saline-constitutive expression of the RelA (p65) subunit. ET did not induce the DNA-binding activity of NF-kB in the diencephalon (DE) or substantia nigra (SN) at various time points, when compared with baseline levels of expression. Intraperitoneal (IP) injections of ET in vivo upregulated the expression of NF-kB subunits in the liver and reduced the cytosolic accumulation of IkB-a by inducing pIkB-a. Furthermore, IP pretreatment with thymulin followed by ICV

关键词： Anti-Inflammatory Hippocampus IkB Inflammation intracerebroventricular Intraperitoneal Lipopolysaccharide NF-kB Thymulin

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Atsttrin reduces lipopolysaccharide-induced neuroinflammation by inhibiting the nuclear factor kappa B signaling pathway

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Neural Regeneration Research 2019年第11期14卷 1994-2002页

作者： Lian Liu Yuan Qu Yi Liu Hua Zhao He-Cheng Ma Ahmed Fayyaz Noor Chang-Jiao Ji Lin Nie Meng Si Lei Cheng Department of Orthopedics Qilu Hospital of Shandong UniversityJinanShandong ProvinceChina Department of Orthopedics Qilu Children's Hospital of Shandong UniversityJinanShandong ProvinceChina Department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Chemistry University of Massachusetts LowellLowellMAUSA Department of Orthopedics the Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinanShandong ProvinceChina

Progranulin is closely related to neuronal survival in a neuroinflammatory mouse model and attenuates inflammatory reactions. Atsttrin is an engineered protein composed of three progranulin fragments and has been shown to have an effect similar to that of progranulin. Atsttrin has anti-inflammatory actions in multiple arthritis mouse models, and it protects against further arthritis development. However, whether Atsttrin has a role in neuroinflammation remains to be elucidated. In this study, we produced a neuroinflammatory mouse model by intracerebroventricular injection of 1 μL lipopolysaccharide(10 μg/μL). Atsttrin(2.5 mg/kg) was administered via intraperitoneal injection every 3 days over a period of 7 days before intracerebroventricular injection of 1 μL lipopolysaccharide(10 μg/μL). In addition, astrocyte cultures were treated with 0, 100 or 300 ng/mL lipopolysaccharide, with 200 ng/mL Atsttrin simultaneously. Immunohistochemistry, enzyme-linked immunosorbent assay and real-time reverse transcription-polymerase chain reaction were performed to examine the protein and mRNA levels of inflammatory mediators and to assess activation of the nuclear factor kappa B signaling pathway. Progranulin expression in the brain of wild-type mice and in astrocyte cultures was increased after lipopolysaccharide administration. The protein and mRNA expression levels of tumor necrosis factor-α, interleukin-1β and inducible nitric oxide synthase were increased in the brain of progranulin knockout mice after lipopolysaccharide administration. Atsttrin treatment reduced the lipopolysaccharide-induced increase in the protein and mRNA levels of tumor necrosis factor-α, interleukin-1β, matrix metalloproteinase-3 and inducible nitric oxide synthase in the brain of progranulin knockout mice. Atsttrin also reduced the expression of cyclooxygenase-2, inducible nitric oxide synthase and matrix metalloproteinase 3 mRNA in lipopolysaccharide-treated astrocytes in vitro, and decreased the conc

关键词： nerve regeneration progranulin Atsttrin neuroinflammation inflammatory cytokines lipopolysaccharide intracerebroventricular injection astrocyte nuclear factor kappa B signaling pathway progranulin knockout mouse cerebrospinal fluid neural regeneration

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Role of nesfatin-1 in a rat model of visceral hypersensitivity

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World Journal of Gastroenterology 2013年第22期19卷 3487-3493页

作者： Fang-Yuan Jia Xue-Liang Li Tian-Nv Li Jing Wu Bi-Yun Xie Lin Lin Department of Gastroenterology the First Affiliated Hospital of Nanjing Medical University Department of PET/CT the First Affiliated Hospital of Nanjing Medical University

AIM: To explore the role of nesfatin-1 on irritable bowel syndrome (IBS)-like visceral hypersensitivity. METHODS: The animal model of IBS-like visceral hypersensitivity was induced by intracolonic infusion of 0.5% acetic acid (AA) in saline once daily from postnatal days 8-21. Experiments were performed when rats became adults. The visceral sensitivity of rats was evaluated by abdominal withdrawal reflex (AWR) and electromyographic (EMG) activity of the external oblique muscle to graded colorectal distension. The content of nesfatin-1 in serum was determined using enzyme-linked immunosorbent assay. After implantation of an intracerebroventricular (ICV) cannula and two electrodes into the external oblique muscle, model rats were randomly divided into four groups. Animals then received ICV injection of 8 μg of anti-nesfatin-1/ nucleobindin-2 (NUCB2), 50 μg of α-helical cortico-tropin releasing factor (CRF) 9-41 (non-selective CRF receptor antagonist), 50 μg of NBI-27914 (selective CRF1 receptor antagonist) or 5 μL of vehicle. After 1 h of ICV administration, visceral sensitivity of each group was measured again, and comparisons between groups were made. RESULTS: Rats treated with AA showed higher mean AWR scores and EMG activity at all distension pressures compared with controls (P < 0.05). On histopathologic examination, no evidence of inflammation or abnormalities in structure were noted in the colon of either control or AA-treated groups. Myeloperoxidase values were not significantly different between the two groups. The level of nesfatin-1 in serum was significantly higher in the AA-treated group than in the control group (5.34 ± 0.37 ng/mL vs 4.81 ± 0.42 ng/mL, P < 0.01). Compared with rats injected with vehicle, rats which received ICV anti-nesfatin-1/NUCB2, α-helical CRF9-41 or NBI-27914 showed decreased mean AWR scores and EMG activity at all distension pressures (P < 0.05). CONCLUSION: Nesfatin-1 may be associated with IBS-like visceral hypersensitivity, whic

关键词： Irritable bowel syndrome Nesfatin-1 Visceral hypersensitivity Corticotropin releasing factor intracerebroventricular injection

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