Predictive validity of behavioural animal models for chronic pain.


:Rodent models of chronic pain may elucidate pathophysiological mechanisms and identify potential drug targets, but whether they predict clinical efficacy of novel compounds is controversial. Several potential analgesics have failed in clinical trials, in spite of strong animal modelling support for efficacy, but there are also examples of successful modelling. Significant differences in how methods are implemented and results are reported means that a literature-based comparison between preclinical data and clinical trials will not reveal whether a particular model is generally predictive. Limited reports on negative outcomes prevents reliable estimate of specificity of any model. Animal models tend to be validated with standard analgesics and may be biased towards tractable pain mechanisms. But preclinical publications rarely contain drug exposure data, and drugs are usually given in high doses and as a single administration, which may lead to drug distribution and exposure deviating significantly from clinical conditions. The greatest challenge for predictive modelling is, however, the heterogeneity of the target patient populations, in terms of both symptoms and pharmacology, probably reflecting differences in pathophysiology. In well-controlled clinical trials, a majority of patients shows less than 50% reduction in pain. A model that responds well to current analgesics should therefore predict efficacy only in a subset of patients within a diagnostic group. It follows that successful translation requires several models for each indication, reflecting critical pathophysiological processes, combined with data linking exposure levels with effect on target.


Br J Pharmacol


Berge OG




Has Abstract


2011-10-01 00:00:00












  • The dependence of excitatory junction potential amplitude on the external calcium concentration in narcotic tolerant mouse vas deferens.

    abstract::The dependence of neurotransmitter secretion on external calcium ions during development of opiate tolerance in the mouse vas deferens was studied. The writhing response of mice to an i.p. injection of acetylcholine was inhibited by morphine. Reversal of this antinociceptive effect of morphine during chronic treatment...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Einstein R,Lavidis NA

    更新日期:1984-12-01 00:00:00

  • The effects of long-term infusion of salbutamol, diltiazem and nifedipine on uterine contractions in the ovariectomized, post-partum rat.

    abstract::The sensitivity of the uterus to the inhibition of contractions by salbutamol, diltiazem or nifedipine was assessed in the ovariectomized, post-partum rat by dose-response curves following bolus intravenous (i.v.) administration. These tests were performed before (day 1), immediately after a 20 h i.v. infusion of salb...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Abel MH,Hollingsworth M

    更新日期:1986-07-01 00:00:00

  • On the preparation of highly purified slow reacting substance of anaphylaxis (SRS-A) from biological extracts.

    abstract::1 Very highly purified (greater than 100,000 u/mg) slow reacting substance of anaphylaxis (SRS-A) has been prepared by reversed phase high pressure liquid chromatographic (HPLC) techniques. 2 High resolution liquid chromatography suggests that SRS-A may exist in at least three distinct forms which are possible tautome...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Blackwell GJ,Burka JF,Flower RJ,Torkington P

    更新日期:1980-01-01 00:00:00

  • Anti-inflammatory, membrane-stabilizing interactions of salmeterol with human neutrophils in vitro.

    abstract::1. We have investigated the effects of salmeterol (0.3-50 microM) on several pro-inflammatory activities of human neutrophils in vitro. 2. Oxidant production by FMLP- and calcium ionophore (A23187)-activated neutrophils was particularly sensitive to inhibition by low concentrations (0.3-3 microM) of salmeterol, while ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Anderson R,Feldman C,Theron AJ,Ramafi G,Cole PJ,Wilson R

    更新日期:1996-04-01 00:00:00

  • Epithelial Na⁺ channel activity in human airway epithelial cells: the role of serum and glucocorticoid-inducible kinase 1.

    abstract:BACKGROUND AND PURPOSE:Glucocorticoids appear to control Na⁺ absorption in pulmonary epithelial cells via a mechanism dependent upon serum and glucocorticoid-inducible kinase 1 (SGK1), a kinase that allows control over the surface abundance of epithelial Na⁺ channel subunits (α-, β- and γ-ENaC). However, not all data s...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Watt GB,Ismail NA,Caballero AG,Land SC,Wilson SM

    更新日期:2012-06-01 00:00:00

  • Thapsigargin-induced endothelium-dependent triphasic regulation of vascular tone in the porcine renal artery.

    abstract::1. To elucidate the role of thapsigargin-induced Ca2+ entry in endothelial cells in the regulation of vascular tone, changes in Ca2+ and force of smooth muscle were simultaneously monitored in fura-2-loaded strips of porcine renal artery. 2. During phenylephrine-induced sustained contraction, thapsigargin caused an en...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Ihara E,Hirano K,Nishimura J,Nawata H,Kanaide H

    更新日期:1999-10-01 00:00:00

  • Urocortin-induced endothelium-dependent relaxation of rat coronary artery: role of nitric oxide and K+ channels.

    abstract::1. The mechanisms underlying the vasodilator response to urocortin are incompletely understood. The present study was designed to examine the role of endothelial nitric oxide and Ba(2+)-sensitive K(+) channels in the endothelium-dependent component of urocortin-induced relaxation in the rat left anterior descending co...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Huang Y,Chan FL,Lau CW,Tsang SY,He GW,Chen ZY,Yao X

    更新日期:2002-03-01 00:00:00

  • The mechanism for the contraction induced by leukotriene C4 in guinea-pig taenia coli.

    abstract::The mechanism underlying the LTC(4)-induced contraction of guinea-pig taenia coli was determined using the simultaneous measurements of [Ca(2+)](i) and force in whole muscle preparations. Additional experiments were performed in receptor coupled permeabilized preparation. For comparison purposes, the contraction which...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Ieiri S,Nishimura J,Hirano K,Suita S,Kanaide H

    更新日期:2001-06-01 00:00:00

  • The effect of a tachykinin NK1 receptor antagonist, SR140333, on oedema formation induced in rat skin by venom from the Phoneutria nigriventer spider.

    abstract::1. The possibility that tachykinin NK1 receptors are involved in the plasma extravasation evoked by intradermal (i.d.) injection of Phoneutria nigriventer venom (PNV) in rat dorsal skin in vivo has been investigated. 2. Local oedema formation induced by the i.d. injection of test agents was measured by the extravascul...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Palframan RT,Costa SK,Wilsoncroft P,Antunes E,de Nucci G,Brain SD

    更新日期:1996-05-01 00:00:00

  • Number of nitrate groups determines reactivity and potency of organic nitrates: a proof of concept study in ALDH-2-/- mice.

    abstract:BACKGROUND AND PURPOSE:Mitochondrial aldehyde dehydrogenase (ALDH-2) has been shown to provide a pathway for bioactivation of organic nitrates and to be prone to desensitization in response to highly potent, but not to less potent, nitrates. We therefore sought to support the hypothesis that bioactivation by ALDH-2 cri...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Wenzel P,Hink U,Oelze M,Seeling A,Isse T,Bruns K,Steinhoff L,Brandt M,Kleschyov AL,Schulz E,Lange K,Weiner H,Lehmann J,Lackner KJ,Kawamoto T,Münzel T,Daiber A

    更新日期:2007-02-01 00:00:00

  • Dual role of nitrergic neurotransmission in the bed nucleus of the stria terminalis in controlling cardiovascular responses to emotional stress in rats.

    abstract:BACKGROUND AND PURPOSE:The aim of the present study was to assess the interaction of nitrergic neurotransmission within the bed nucleus of the stria terminalis (BNST) with local glutamatergic and noradrenergic neurotransmission in the control of cardiovascular responses to acute restraint stress in rats. EXPERIMENTAL ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Barretto-de-Souza L,Adami MB,Benini R,Crestani CC

    更新日期:2018-10-01 00:00:00

  • DNA mismatch repair (MMR)-dependent 5-fluorouracil cytotoxicity and the potential for new therapeutic targets.

    abstract::The metabolism and efficacy of 5-fluorouracil (FUra) and other fluorinated pyrimidine (FP) derivatives have been intensively investigated for over fifty years. FUra and its antimetabolites can be incorporated at RNA- and DNA-levels, with RNA level incorporation provoking toxic responses in human normal tissue, and DNA...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审


    authors: Li LS,Morales JC,Veigl M,Sedwick D,Greer S,Meyers M,Wagner M,Fishel R,Boothman DA

    更新日期:2009-10-01 00:00:00

  • The impact of cytokines on the expression of drug transporters, cytochrome P450 enzymes and chemokine receptors in human PBMC.

    abstract:BACKGROUND AND PURPOSE:The function of transporters in peripheral blood mononuclear cells (PBMC) has been characterized, but less is known about cytochrome P450 (CYP) enzyme function in these cells. Given that cytokines are dysregulated in many diseases, the purpose of this work was to assess the impact of cytokines on...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Liptrott NJ,Penny M,Bray PG,Sathish J,Khoo SH,Back DJ,Owen A

    更新日期:2009-02-01 00:00:00

  • Delphinidin and cyanidin inhibit PDGF(AB)-induced VEGF release in vascular smooth muscle cells by preventing activation of p38 MAPK and JNK.

    abstract:BACKGROUND AND PURPOSE:Red wine polyphenols (RWPs) inhibit the expression of vascular endothelial growth factor (VEGF), a major pro-angiogenic and pro-atherosclerotic factor, in vascular smooth muscle cells (VSMCs). The aim of this study was to identify which red wine polyphenols were inhibitory and to determine the me...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Oak MH,Bedoui JE,Madeira SV,Chalupsky K,Schini-Kerth VB

    更新日期:2006-10-01 00:00:00

  • Functional expression of the serotonin 5-HT7 receptor in human glioblastoma cell lines.

    abstract::Serotonin 5-HT(7) receptors are present in astrocytes. Understanding their role in this type of cell would greatly benefit from the identification of astroglial cell lines expressing this receptor type. The aim of the present study was to assess the expression of native 5-HT(7) receptors and 5-HT(7) receptor mRNA in a...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Mahé C,Bernhard M,Bobirnac I,Keser C,Loetscher E,Feuerbach D,Dev KK,Schoeffter P

    更新日期:2004-10-01 00:00:00

  • The expression of N-methyl-D-aspartate-receptor-mediated component during epileptiform synaptic activity in hippocampus.

    abstract::1 The possible involvement of N-methyl-D-aspartate (NMDA)-receptors in epileptiform synaptic activity in the kainic acid (KA) lesioned hippocampus was investigated. In this chronic model of epilepsy there is a loss of both the early and the late components of synaptic inhibition as well as changes in the membrane prop...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Ashwood TJ,Wheal HV

    更新日期:1987-08-01 00:00:00

  • Participation of mitogen-activated protein kinase in thapsigargin- and TPA-induced histamine production in murine macrophage RAW 264.7 cells.

    abstract::1. Stimulation of the murine macrophage cell line RAW 264.7 with thapsigargin, an endomembrane Ca(2+)-ATPase inhibitor, induced histamine production in a time- and concentration-dependent manner. 2. The protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), also enhanced histamine production. 3. alpha...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Shiraishi M,Hirasawa N,Kobayashi Y,Oikawa S,Murakami A,Ohuchi K

    更新日期:2000-02-01 00:00:00

  • Blockade of the development of morphine tolerance by U-50,488, an AVP antagonist or MK-801 in the rat hippocampal slice.

    abstract::1. In this study, we investigated the effects of different drugs (a kappa-opioid receptor agonist U-50,488, a vasopressin receptor antagonist dPTyr(Me)AVP or an N-methyl-D-aspartate (NMDA) receptor antagonist MK-801) on the development of morphine tolerance in rat hippocampal slices. 2. Hippocampal slices (450 microm)...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Su MT,Lin WB,Lue WM,Cheng CY,Tao PL

    更新日期:1998-02-01 00:00:00

  • Antagonism of tone and prostaglandin-mediated responses in a tracheal preparation by indomethacin and SC-19220.

    abstract::1 The effects of the prostaglandin synthetase inhibitor, indomethacin and the prostaglandin antagonist SC-19220 (1-acetyl-2-[8-chloro-10,11-dihydrodibenz (b,f) (1,4)oxazepine-10-carbonyl] hydrazine), were examined on the tone of the guinea-pig isolated tracheal preparation and on the responses of the preparation to pr...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Farmer JB,Farrar DG,Wilson J

    更新日期:1974-12-01 00:00:00

  • Renal effects of intrathecally injected tachykinins in the conscious saline-loaded rat: receptor and mechanism of action.

    abstract::1. The effects of intrathecally (i.t.) injected substance P (SP), neurokinin A (NKA), [beta-Ala8]NKA (4-10) and [MePhe7]neurokinin B (NKB) at T13 thoracic spinal cord level were investigated on renal excretion of water, sodium and potassium in the conscious saline-loaded rat. Antagonists selective for NK1 (RP 67580), ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Yuan YD,Couture R

    更新日期:1997-07-01 00:00:00

  • Evidence for a M(1) muscarinic receptor on the endothelium of human pulmonary veins.

    abstract::1. To characterize the muscarinic receptors on human pulmonary veins associated with the acetylcholine (ACh)-induced relaxation, isolated venous and arterial preparations were pre-contracted with noradrenaline (10 microM) and were subsequently challenged with ACh in the absence or presence of selective muscarinic anta...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Walch L,Gascard JP,Dulmet E,Brink C,Norel X

    更新日期:2000-05-01 00:00:00

  • Short-term desensitization of guinea-pig taenia caecum induced by carbachol occurs at intracellular Ca stores and that by histamine at H1-receptors.

    abstract::1. In Ca-free solution, the contractile response of guinea-pig taenia caecum to 10(-4) M carbachol was mediated through muscarinic receptors and was reduced time-dependently by desensitization with 10(-4) M carbachol, but not 10(-4) M histamine. On the other hand, the response to 10(-4) M histamine was shown to be med...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Hishinuma S,Uchida MK

    更新日期:1988-07-01 00:00:00

  • Evidence for the involvement of different receptor subtypes in the pre- and postjunctional actions of angiotensin II at rat sympathetic neuroeffector sites.

    abstract::1. The effects of the nonpeptide angiotensin II receptor (AT) antagonists losartan and PD 123319 on actions of angiotensin II in the rat caudal artery and rat vas deferens preparations were investigated. 2. Angiotensin II (1.0 microM) increased perfusion pressure in isolated segments of the rat caudal artery. This inc...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Cox SL,Ben A,Story DF,Ziogas J

    更新日期:1995-03-01 00:00:00

  • Cardiotoxic effects of fenfluramine hydrochloride on isolated cardiac preparations and ventricular myocytes of guinea-pigs.

    abstract::The cardiotoxic effects of fenfluramine hydrochloride on mechanical and electrical activity were studied in papillary muscles, Purkinje fibres, left atria and ventricular myocytes of guinea-pigs. Force of contraction (f(c)) was measured isometrically, action potentials and maximum rate of rise of the action potential ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Rajamani S,Studenik C,Lemmens-Gruber R,Heistracher P

    更新日期:2000-03-01 00:00:00

  • Central effects of the cannabinoid receptor agonist WIN55212-2 on respiratory and cardiovascular regulation in anaesthetised rats.

    abstract::1 The primary aim was to study the central respiratory effects of cannabinoids (CB). To this end, the cannabinoid receptor agonist WIN55212-2 was injected into the cisterna magna of urethane-anaesthetised rats and changes in respiratory parameters were observed. The secondary aim was to observe the centrally elicited ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Pfitzer T,Niederhoffer N,Szabo B

    更新日期:2004-07-01 00:00:00

  • Adenosine potentiates immunological histamine release from rat mast cells by a novel cyclic AMP-independent cell-surface action.

    abstract::Adenosine enhanced histamine release and prolonged the adenosine 3':5'-cyclic monophosphate (cyclic AMP) response in purified rat peritoneal mast cells following immunological challenge. The effect on the cyclic AMP response, which was blocked by 8-phenyltheophylline, probably results from an interaction with A2-purin...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Church MK,Hughes PJ

    更新日期:1985-05-01 00:00:00

  • Activation of μ-opioid receptors by MT-45 (1-cyclohexyl-4-(1,2-diphenylethyl)piperazine) and its fluorinated derivatives.

    abstract:BACKGROUND AND PURPOSE:A fluorinated derivative (2F-MT-45) of the synthetic μ-opioid receptor agonist MT-45 (1-cyclohexyl-4-(1,2-diphenylethyl)piperazine) was recently identified in a seized illicit tablet. While MT-45 is a Class A drug, banned in a number of countries, nothing is known about the pharmacology of 2F-MT-...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Baptista-Hon DT,Smith M,Singleton S,Antonides LH,Nic Daeid N,McKenzie C,Hales TG

    更新日期:2020-08-01 00:00:00

  • Endothelium-dependent contractions in hypertension.

    abstract::1. Endothelial cells, under given circumstances, can initiate contraction (constriction) of the vascular smooth muscle cells that surround them. Such endothelium-dependent, acute increases in contractile tone can be due to the withdrawal of the production of nitric oxide, to the production of vasoconstrictor peptides ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审


    authors: Vanhoutte PM,Feletou M,Taddei S

    更新日期:2005-02-01 00:00:00

  • Behavioural and pharmacokinetic studies in the monkey (Macaca mulatta) with diazepam, nordiazepam and related 1,4-benzodiazepines.

    abstract::1. Behavioural activity (delayed differentiation and spatial delayed alternation) and pharmacokinetics of diazepam and its metabolites, N-desmethyldiazepam (nordiazepam), 3-hydroxydiazepam (temazepam) and 3-hydroxy-N-desmethyldiazepam (oxazepam), and of dipotassium clorazepate (clorazepate), were studied in the monkey...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Curry SH,Whelpton R,Nicholson AN,Wright CM

    更新日期:1977-11-01 00:00:00

  • Charybdotoxin-sensitive K+ channels regulate the myogenic tone in the resting state of arteries from spontaneously hypertensive rats.

    abstract::1. To determine the possible role of Ca(2+)-activated K+ (KCa) channels in the regulation of resting tone of arteries from spontaneously hypertensive rats (SHR), the effects of agents which interact with these channels on tension and 86Rb efflux were compared in endothelium-denuded strips of carotid, femoral and mesen...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Asano M,Masuzawa-Ito K,Matsuda T

    更新日期:1993-01-01 00:00:00