Browsing by Subject "BLOCK"

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  • Chen, Zuyue; Wei, Hong; Sagalajev, Boriss; Koivisto, Ari; Pertovaara, Antti (2019)
    Background: The central amygdaloid nucleus (CeA) is involved in processing and descending regulation of pain. Amygdaloid mechanisms underlying pain processing and control are poorly known. Here we tested the hypothesis that perioperative CeA administration of tetrapentylammonium (TPA), a non-selective THIK-1 channel blocker and thereby inhibitor of microglia, attenuates development of chronic neuropathic pain and comorbid anxiety-like behavior. Methods: Rats with a spared nerve injury (SNI) model of neuropathy or sham operation had a chronic cannula for drug microinjections into the CeA or a control injection site. Monofilament test was used to evaluate pain, and light-dark box (LDB) to assess anxiety. Results: Perioperative CeA treatment with TPA (30 mu g/day up to the third postoperative day, D3) significantly attenuated the development of pain and anxiety-like behavior. In the late phase (> D14), CeA administration of TPA (3-30 mu g) failed to influence pain. Perioperative minocycline (microglia inhibitor; 25 mu g), MK-801 (an N-Methyl-D-aspartate receptor antagonist; 0.1 mu g), vehicle or TPA in a control injection site failed to attenuate pain development. Conclusions: Perioperative treatment of the CeA with TPA delayed development of neuropathic pain and comorbid anxiety-like behavior, while TPA treatment failed to influence maintenance of established neuropathic pain. The failures to attenuate pain development with CeA administrations of minocycline or MK-801 do not support the hypothesis that the TPA-induced prophylactic effect was due to inhibition of amygdaloid microglia or N-methyl-D-aspartate receptors. While TPA in the CeA proved to have a prophylactic effect on SNI-induced pain behavior, the underlying mechanism still remains to be studied. (c) 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.
  • Schütt, Jorina Marlena; Whipp, David Michael (2020)
    Strain partitioning onto margin-parallel thrust and strike-slip faults is a common process at obliquely convergent plate margins, leading to the formation and migration of crustal slivers. The degree of strain partitioning and rate of sliver migration can be linked to several factors including the angle of convergence obliquity, the dip angle of subduction, frictional coupling between the plates and the strength of the upper plate, among others. Although these factors are known to be important, their relative influence on strain partitioning is unclear, particularly at natural margins where the factors often vary along strike. Here we use a 3-D mechanical finite-element model to investigate the relationship between continental crustal strength, the convergence obliquity angle, the subduction angle, and strain partitioning in the Northern Volcanic Zone (NVZ) of the Andes (5 degrees N-3 degrees S). In the NVZ the subduction dip and obliquity angles both vary along strike, weaknesses in the continental crust may be present in suture zones or regions of arc volcanism, and strain partitioning is only observed in some regions. Thus, it is an ideal location to gain insight in which of the factors have the largest influence on deformation and sliver formation in the upper plate. Our numerical experiments confirm that a moderately high obliquity angle is needed for partitioning and that a continental crustal weakness is also required for movement of a coherent continental sliver at rates similar to geodetic observations from the NVZ. In contrast, the subduction dip angle is only of secondary importance in controlling strain partitioning behavior. Key Points Factors influencing formation of continental slivers investigated using 3-D numerical models of finite-width oblique subduction systems Model results indicate that convergence obliquity and the presence of weak zones in the upper plate are key to formation of well-defined slivers Model predictions are in good agreement with geodetic observations of sliver motion in the Northern Volcanic Zone of the Andes
  • Ahlström, Sirkku; Bergman, Paula; Jokela, Ritva; Ottensmann, Linda; Ahola-Olli, Ari; Pirinen, Matti; Olkkola, Klaus T.; Kaunisto, Mari A.; Kalso, Eija (2021)
    Background: Rocuronium, a common neuromuscular blocking agent, is mainly excreted unchanged in urine (10-25%) and bile ( 70%). Age, sex, liver blood flow, smoking, medical conditions, and ethnic background can affect its pharmacological actions. However, reasons for the wide variation in rocuronium requirements are mostly unknown. We hypothesised that pharmacogenetic factors might explain part of the variation. Methods: One thousand women undergoing surgery for breast cancer were studied. Anaesthesia was maintained with propofol (50-100 mg kg(-1) min(-1)) and remifentanil (0.05-0.25 mg kg(-1) min(-1)). Neuromuscular block was maintained with rocuronium to keep the train-of-four ratio at 0-10%. DNA was extracted from peripheral blood and genotyped with a next-generation genotyping array. The genome-wide association study (GWAS) was conducted using an additive linear regression model with PLINK software. The FINEMAP tool and data from the Genotype-Tissue Expression project v8 were utilised to study the locus further. Results: The final patient population comprised 918 individuals. Of the clinical variables tested, age, BMI, ASA physical status, and total dose of propofol correlated significantly (all P Conclusions: Genetic variation in the gene SLCO1A2, encoding OATP1A2, an uptake transporter, accounted for 4% of the variability in rocuronium consumption. The underlying mechanism remains unknown.