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| 1 | Effect of acetyl-L-carnitine on hypersensitivity in acute recurrent caerulein-induced pancreatitis and microglial activation along the brain’s pain circuitry显示文摘BACKGROUND Acute pancreatitis(AP)and recurring AP are serious health care problems causing excruciating pain and potentially lethal outcomes due to sepsis.The validated caerulein-(CAE)induced mouse model of acute/recurring AP produces secondary persistent hypersensitivity and anxiety-like behavioral changes for study.AIM To determine efficacy of acetyl-L-carnitine(ALC)to reduce pain-related behaviors and brain microglial activation along the pain circuitry in CAE-pancreatitis.METHODS Pancreatitis was induced with 6 hly intraperitoneal(i.p.)injections of CAE(50μg/kg),3 d a week for 6 wk in male C57BL/6J mice.Starting in week 4,mice received either vehicle or ALC until experiment’s end.Mechanical hypersensitivity was assessed with von Frey filaments.Heat hypersensitivity was determined with the hotplate test.Anxiety-like behavior was tested in week 6 using elevated plus maze and open field tests.Microglial activation in brain was quantified histologically by immunostaining for ionized calcium-binding adaptor molecule 1(Iba1).RESULTS Mice with CAE-induced pancreatitis had significantly reduced mechanical withdrawal thresholds and heat response latencies,indicating ongoing pain.Treatment with ALC attenuated inflammation-induced hypersensitivity,but hypersensitivity due to abdominal wall injury caused by repeated intraperitoneal injections persisted.Animals with pancreatitis displayed spontaneous anxiety-like behavior in the elevated plus maze compared to controls.Treatment with ALC resulted in increased numbers of rearing activity events,but time spent in“safety”was not changed.After all the abdominal injections,pancreata were translucent if excised at experiment’s end and opaque if excised on the subsequent day,indicative of spontaneous healing.Post mortem histopathological analysis performed on pancreas sections stained with Sirius Red and Fast Green identified wide-spread fibrosis and acinar cell atrophy in sections from mice with CAE-induced pancreatitis that was not rescued by treatment with ALC.Microglial Iba1 immunostaining was significantly increased in hippocampus,thalamus(intralaminar nuclei),hypothalamus,and amygdala of mice with CAE-induced pancreatitis compared to naïve controls but unchanged in the primary somatosensory cortex compared to naïves.CONCLUSION CAE-induced pancreatitis caused increased pain-related behaviors,pancreatic fibrosis,and brain microglial changes.ALC alleviated CAE-induced mechanical and heat hypersensitivity but not abdominal wall injury-induced hypersensitivity caused by the repeated injections. | Sabrina L McIlwrath Marlene E Starr Abigail E High Hiroshi Saito Karin N Westlund | 2021 | World Journal of Gastroenterology2021，27，9： | 2 |
| 2 | GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils显示文摘 | Hattori N Saito T Yagyu T | 2001 | Clin Endocrinol Metab2001，86，9： | 2 |
| 3 | Mitochondrial Ca^2+-activated K^+ channels in cardiac myocytes: a mechanism of the cardioprotective effect and modulation by protein kinase A 显示文摘 | Sato T Saito T Saegusa N | 2005 | Circulation2005，111，2： | 1 |
| 4 | Different serum concentrations of steady - state valproic acid in two sustained - release formulations 显示文摘 | Yasui -Furukori N Saito M Nakagami T | 2007 | Psrchiatry Clin Neurosci2007，61，3： | 1 |
| 5 | Antioxidant activity and xanthine oxidase inhibition activity of reductic acid: ascorbic acid analogue显示文摘 | Mashino T Takigawa Y Saito N | 2000 | Bioorg Med Chem Lett2000，10，24： | 1 |
| 6 | The transsphenoidal removal of nonfunetioning pituitary adenomas with suprasellar extensions: the open sella methold and intentionally staged operation 显示文摘 | Saito K Kuwayama A Yamamoto N | 1995 | Neurosurgery1995，36，4： | 1 |
| 7 | Vaccination with tumor cell lysate-plused dendritic cell augment the effect of IFN-beta gene therapy for malignant glima in an experimental mose intracranial glioma显示文摘 | Saito R Mizuno M Nakahara N | 2004 | Cancer2004，111，5： | 1 |
| 8 | Total and face prostate-specific antigen indexes in prostate cancer screening:value and limitation for Japanese populations显示文摘 | Hara N Kitamura Y Saito T | 2006 | Asian J Androl2006，8，4： | 1 |
| 9 | Aretigenin from Fructus arctii Is a Novel Suppressor of Heat Shock Response in Mammalian Cells显示文摘 | Ishihara K Yanmgishi N Saito Y | 2006 | Cell Stress Chaperon2006，11，2： | 1 |
| 10 | Structure and antitumor activity of the less branched derivatives of an alkali-soluble glucan isolated from Omphalia lapidescen 显示文摘 | Saito K Nishijima M Ohno N | 1992 | Chemical & Pharmaceutical Bulletin1992，40，1： | 1 |
| 11 | Hypertrophic responses to cardiotrophin-1 are not mediated by STAT3, but via a MEK5/ ERK5 pathway in cultured cardiomyotes 显示文摘 | Takahashi N Saito Y Kuwahara K | 2005 | J Mol Cell Cardio2005，38，： | 1 |
| 12 | Immunosuppre- ssive effect of cholera toxin B on allergic conjunctivitis model in guinea pig 显示文摘 | SAITO K SHOJI J INADA N | 2001 | Jpn J Ophthalmol2001，45，4： | 1 |
| 13 | Identification of Parentage of Japanese Pear Housui显示文摘 | SAWAMURA Y SAITO T TAKADA N | 2004 | J Jpn Soc Hort Sci2004，73，： | 1 |
| 14 | Relationships between brachial artery flow mediated dilation and carotid artery intima-media thickness in patients with suspected coronary artery disease显示文摘 | Furumoto T Fujii S Saito N | 2002 | Jpn Heart J2002，43，2： | 1 |
| 15 | Time Delays and Chaos in Two Competition System显示文摘 | A Shibata N Saito | 1980 | Math Biosci1980，51，： | 1 |
| 16 | Endothelial nitric oxide synthase gene is positively associated with essential hypertension显示文摘 | MIYAMOTO Y SAITO Y KAJIYAMA N | 1998 | Hypertension1998，32，： | 1 |
| 17 | Efficient gene transfer into the embryonic mouse brain using in vivo electroporation显示文摘 | SAITO T NAKATSUJI N | 2001 | Dev Biol2001，240，1： | 1 |
| 18 | Photocatalyst releasing hydrogen from water-Enhancingcatalytic performance holds promise for hydrogen production bywater splitting in sunlight显示文摘 | Maeda K Teramura K Lu D Takata T Saito N Inoue Y Do-men K | 2006 | Nature2006，440，7082： | 1 |
| 19 | Collagen as the majoreible component of sea cucumber {Stichopus japonicus)显示文摘 | SAITO M KUNISAKI N URANO N | 2002 | Journal ofFood Science2002，67，： | 1 |
| 20 | Efficient gene transfer into the embryonic mouse brain using in vivo electroporation显示文摘 | Saito T Nakatsuji N | 2001 | Dev Biol2001，240，1： | 1 |
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