Abstract：
:Berend Olivier has had a long-standing interest in the utility of animal models for a wide variety of therapeutic indications. His work has spanned multiple types of models, blending ethological, or species typical and naturalistic behaviors, along with methodologies based on learned behavior. He has consistently done so, from an analytical as well as predictive perspective, and has made multiple contributions while working in both the pharmaceutical industry and within an academic institution. Although focused primarily on psychiatric disorders, Berend has conducted research in the area of pain in humans and in animals, demonstrating an expansive appreciation for the breadth, scope and significance of the science and applications of the discipline of pharmacology to these diverse areas. This review focuses on the use of animal models in pain research from the perspective of the long-standing deficiencies in the development of therapeutics in this area and from a preclinical perspective where the translational weaknesses have been quite problematic. The challenges confronting animal models of pain, however, are not unique to this area of research, as they cut across several therapeutic areas. Despite the deficiencies, failures and concerns, existing animal models of pain continue to be of widespread use and are essential to progress in pain research as well as in other areas. Although not focusing on specific animal models of pain, this paper seeks to examine general issues facing the use of these models. It does so by exploring alternative approaches which capture recent developments, which build upon principles and concepts we have learned from Berend's contributions, and which provide the prospect of helping to address the absence of novel therapeutics in this area.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Barrett JEdoi
10.1016/j.ejphar.2014.11.046subject
Has Abstractpub_date
2015-04-15 00:00:00pages
183-90eissn
0014-2999issn
1879-0712pii
S0014-2999(15)00017-5journal_volume
753pub_type
杂志文章,评审abstract：:Chronic lithium treatment was examined for effects on the blood pressure of spontaneously hypertensive rats (SHRs). Treated rats were allowed continuous access to a pelleted lithium diet (1.7 g LiCl (40 mmol)/kg diet) for 21 days. Control SHRs were fed a similar diet lacking the lithium. Two groups of control rats wer...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90112-6
更新日期：1981-12-17 00:00:00
abstract：:The effects of 1 mM L-cysteine on sodium nitrite-, 3-morpholinosydnonimine (SIN-1)- and acetylcholine-induced relaxation and cyclic GMP accumulation were studied in isolated noradrenaline-precontracted rat mesenteric arterial rings. L-Cysteine augmented the relaxation and cyclic GMP increase induced by sodium nitrate ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90133-o
更新日期：1992-04-22 00:00:00
abstract：:Identification of the roles of epigenetic alterations in cancers has suggested that different molecules involved in this process are potentially therapeutic targets. Given the role of histone deacetylases (HDACs) enzymes in leukemogenesis, we designed a study to investigate the anti-leukemic property of panobinostat, ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.173050
更新日期：2020-05-15 00:00:00
abstract：:The antinociceptive profile of selected histamine H(2) and histamine H(3) receptor antagonists led to the discovery of improgan, a non-brain-penetrating analgesic agent which does not act on known histamine receptors. Because no chemical congener of improgan has yet been discovered which has both antinociceptive and b...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.08.040
更新日期：2005-10-17 00:00:00
abstract：:Renal mesangial cells exposed to inflammatory cytokines produce high concentrations of nitric oxide (NO) which may exert cytotoxic actions. We report here that glomerular mesangial cells, endothelial cells and epithelial cells in culture are themselves targets for NO and undergo apoptotic cell death upon exposure to h...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(96)00701-7
更新日期：1996-12-12 00:00:00
abstract：:The specificity of action of extrinsic acetylcholine on extrajunctional and junctional receptors in the chick biventer cervicis muscle was studied by determining its ability to protect the responses evoked by acetylcholine and by tetanic nerve stimulation from the blockade by alpha-bungarotoxin, an irreversible bindin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(75)90178-8
更新日期：1975-09-01 00:00:00
abstract：:Painless myocardial infarction is a serious complication of diabetes. The present study examined whether cardiac nociception was altered in the streptozotocin-induced diabetic rat model by assessing intrapericardial capsaicin-evoked electromyography (EMG) responses in the spinotrapezius muscle. Somatic sensitivities t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.10.073
更新日期：2011-01-25 00:00:00
abstract：:The effects of phencyclidine [1-(1-phenylcyclohexyl)-piperidine; PCP] on cardiac action potential duration (APD) were compared to those of some of its derivatives, in strips of isolated frog ventricular muscle perfused with normal Ringer solution. We studied compounds with PCP-like behavioral actions (N-ethyl-1-phenyl...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90578-2
更新日期：1983-04-08 00:00:00
abstract：:This review focuses on alpha(1)-adrenoceptor phosphorylation and function. Most of what is currently known is based on studies on the hamster alpha(1B)-adrenoceptor. It is known that agonist stimulation leads to homologous desensitization of these receptors and current evidence indicates that such decrease in receptor...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0014-2999(99)00896-1
更新日期：2000-02-11 00:00:00
abstract：:The purpose of this study was to delineate the distribution of beta-adrenoceptor density in the cat heart, with an emphasis on areas within the left ventricle. beta-Adrenoceptor densities, determined for hearts obtained from five cats, were not significantly different in the left and rights atria, i.e. 47.6 +/- 7.2 an...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90189-5
更新日期：1986-10-14 00:00:00
abstract：:We investigated whether intracerebroventricular (i.c.v.) infusion of the nitric oxide synthase inhibitor, Nomega-nitro-L-arginine (N-Arg), impairs learning in male Sprague-Dawley rats (2-3 months old) in a 14-unit T-maze. Rats were pretrained in one-way active avoidance to a criterion of 13/15 avoidances of foot shock...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01427-1
更新日期：1998-01-02 00:00:00
abstract：:Intracerebroventricular injection into rats of mast-cell degranulating peptide (MCD), dendrotoxin I (DTXI) and 4-aminopyridine (4-AP), three blockers of a subclass of K+ channels, elicited epileptiform wave bursts and convulsions. Three different types of L-type Ca2+ channel inhibitors (+)PN 200-110, a 1,4-dihydropyri...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90669-9
更新日期：1989-01-24 00:00:00
abstract：:Endogenous Nitric Oxide (NO) plays a key role in the physiological regulation of airway functions. In response to various stimuli activated inflammatory cells (e.g., eosinophils and neutrophils) generate oxidants ("oxidative stress") which in conjunction with exaggerated enzymatic release of NO and augmented NO metabo...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2005.12.057
更新日期：2006-03-08 00:00:00
abstract：:The increases in activity of hepatic thymidylate synthetase and of thymidine kinase, which catalyze the formation of thymidylate via the de novo and salvage pathways, respectively, were significantly suppressed during liver regeneration in rats which had been given alpha-adrenoceptor antagonists (phenoxybenzamine and ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90380-2
更新日期：1985-08-27 00:00:00
abstract：:(5R)-5-hydroxytriptolide (LLDT-8) exhibits strong immunosuppressive activities in vitro and in vivo. Here, we investigated the effects of LLDT-8 on concanavalin A-induced hepatitis. Liver damage was evaluated by serum alanine transaminase (ALT) level and liver histology. The effects of LLDT-8 were determined by measur...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.03.013
更新日期：2006-05-10 00:00:00
abstract：:Prulifloxacin, a new thiazeto-quinoline derivative with antibiotic properties, was evaluated for cardiac risk both in vitro on the ether-à-go-go-related gene (HERG) K+ channel, and in vivo in the conscious dog monitored by telemetry. HERG current was measured from stably transfected human embryonic kidney (HEK) 293 ce...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)02180-0
更新日期：2003-09-05 00:00:00
abstract：:Conscious guinea-pigs received platelet activating factor (PAF, 0.03-0.25 microgram/kg, i.v.) and colloidal carbon (C, tracer for microvascular leakage). Fifteen min later the animal was killed and C-labelled microvessels (leakage) were detected in the mucosal/submucosal region of tracheal and bronchial sections. PAF ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90477-8
更新日期：1987-06-26 00:00:00
abstract：:GABAA and GABAC receptors were studied on cultured or freshly isolated rat retinal bipolar cells. The cells displayed GABA-induced whole-cell currents, which were only partially blocked by high concentrations (100 microM) of the GABAA receptor antagonist bicuculline. The bicuculline-resistant (GABAC) component was ins...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(94)90014-0
更新日期：1994-12-15 00:00:00
abstract：:Cytochrome P450 2J2 (CYP2J2) is highly expressed in human tumors and carcinoma cell lines, and has been implicated in the pathogenesis of human cancers. The aim of this study was to identify a compound that could inhibit the activity of CYP2J2, and to examine its anticancer activity. To identify CYP2J2 inhibitors, 10 ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.07.047
更新日期：2015-10-05 00:00:00
abstract：:N(G)-(Nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthase, induces catalepsy in mice. The objective of the present work was to investigate if serotonergic drugs are able to modulate this effect. Results showed that the cataleptogenic effect of L-NOARG (40 mg/kg) in male albino-Swiss mice was enhanced by ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00493-8
更新日期：1999-08-20 00:00:00
abstract：:Neurodegenerative diseases are the set of progressive, age-related brain disorders, characterized by an excessive accumulation of mutant proteins in the certain regions of the brain. Such changes, collectively identified as causal factors of neurodegeneration, all impact mitochondria, imminently leading to their dysfu...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.12.036
更新日期：2016-02-05 00:00:00
abstract：:Acute kidney injury (AKI) is defined as a rapid loss of kidney function characterised by inflammation and cell death, ultimately leading to further functional and structural renal alterations. Based on experimental and epidemiological pieces of evidence, AKI may progress to chronic kidney disease (CKD) even after a re...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2019.172711
更新日期：2019-12-15 00:00:00
abstract：:A V79 Chinese hamster cell line stably expressing human cytochrome P450 1A1 (CYP1A1) was obtained by chromosomal integration of the human CYP1A1 cDNA under the control of the SV40 early promoter. Chromosomal integration was verified by Southern analysis, and effective transcription of the human CYP1A1 cDNA was demonst...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(93)90052-r
更新日期：1993-10-01 00:00:00
abstract：:Osteoarthritis (OA) is a common yet destructive disease affecting the articular cartilage, and is a major cause of immense suffering and disability for millions of people. Previous studies have shown that triptolide (TPL), an active compound derived from Tripterygium wilfordii, has potent immunosuppressive and anti-in...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.173341
更新日期：2020-09-15 00:00:00
abstract：:Cats were treated for 35 days with flurazepam, 5 mg/kg per day. The drug was administered through a gastric fistula. Ro15-1788, a benzodiazepine antagonist, caused an abstinence syndrome when administered through the gastric fistula 24 h after the last dose of chronic treatment. Abstinence signs included increased mus...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90616-1
更新日期：1982-06-16 00:00:00
abstract：:Blood pressure responses to intrathecal (i.t.) injection of neurochemicals were examined in the fructose-fed rat, an experimental model of metabolic syndrome.Sprague-Dawley rats receiving either tap water or water containing 10% fructose during 8 weeks were anesthetized with sodium pentobarbital. The endocannabinoid a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.02.037
更新日期：2013-04-15 00:00:00
abstract：:Neuropathic pain has been suggested to be resistant to treatment with opiates. Such perceived lack of opioid responsiveness may be due to the dose-range over which specific opioid compounds have been studied as well as the efficacy of these compounds. Dihydroetorphine is a novel opiate that demonstrates significantly ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00531-7
更新日期：1998-09-11 00:00:00
abstract：:To determine the role of protein kinase C in the regulation of intestinal fluid transport, experiments were performed with the rat jejunum in vivo, using the active phorbol ester, 4-beta-phorbol 12-myristate 13-acetate (PMA), as stimulator of protein kinase C. Intraluminally administered PMA dose dependently reversed ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90053-9
更新日期：1990-07-17 00:00:00
abstract：:In the present study, the mechanism of relaxant response of nitric oxide precursor, L-arginine, was investigated in goat isolated coronary artery. L-arginine (1 mM) reversed the U-46619 (1 microM)-induced contraction both in endothelium-intact and endothelium-denuded arterial ring preparations. L-arginine analogues, L...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.03.031
更新日期：2009-05-01 00:00:00
abstract：:We have made extracellular recordings from locus coeruleus neurones contained in a pontine slice preparation. The in vitro technique permits application of known concentrations of drugs in the perfusion medium. Substance P excites locus coeruleus neurones in a concentration-dependent manner. The activity of substance ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90445-4
更新日期：1983-10-14 00:00:00
