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T Meert

Publications and source records attributed to T Meert.

12 recordsLinked to original sources
PubMed2005

A multiparametric assay for quantitative nerve regeneration evaluation.

We introduce an assay for the semi-automated quantification of nerve regeneration by image analysis. Digital images of histological sections of regenerated nerves are recorded using an automated inverted microscope and merged into high-resolution mosaic images representing the entire nerve. These are analysed by a dedicated image-processing package that computes nerve-specific features (e.g. nerve area, fibre count, myelinated area) and fibre-specific features (area, perimeter, myelin sheet thickness). The assay's performance and correlation of the automatically computed data with visually obtained data are determined on a set of 140 semithin sections from the distal part of a rat tibial nerve from four different experimental treatment groups (control, sham, sutured, cut) taken at seven different time points after surgery. Results show a high correlation between the manually and automatically derived data, and a high discriminative power towards treatment. Extra value is added by the large feature set. In conclusion, the assay is fast and offers data that currently can be obtained only by a combination of laborious and time-consuming tests.

Animals↗
PubMed2003

Is the second phase of the formalin test useful to predict activity in chronic constriction injury models? A pharmacological comparison in different species.

This study presents data of several reference drugs in rats and gerbils for both the second phase of the formalin test and the cold allodynia in animals with a constriction injury of the sciatic nerve. A pharmacological validation of the formalin test and the CCI model in gerbils was performed. It was evaluated whether the second phase of the formalin test could be used as a pharmacological screening to predict outcome in the cold plate test in CCI animals. Male Sprague Dawley and Wistar rats and male gerbils were used for both tests. For the formalin test, animals were injected in the right hind paw (5% formalin rat: 0.05 microl; gerbil: 0.01 microl) and flinching and licking or biting were recorded. For CCI testing, a Bennett operation was performed on the left hind paw 7 days before testing. Cold plate allodynia was evaluated before and after drug treatment. In rats, a good correlation between both test conditions for morphine, fentanyl, MK-801 and flunarizine was found. Clonidine tends to have more activity in the second phase of the formalin test, whereas baclofen, tramadol, amitryptiline, ketamine and topiramate demonstrate to be more active in the cold plate. In gerbils, a good correlation between both test conditions for fentanyl and ketoprofen was found. Tramadol and CP-96345 tend to have more activity in the second phase of the formalin test, whereas morphine, SR-48968, SR-142801 and R116301 demonstrates to be more active in the cold plate test. In the present acute test conditions, there is a correlation in the pharmacological activity in rats and gerbils for the tested compounds a correlation between the second phase of the formalin test and the cold allodynia in CCI animals is found. Comparing to human data the screening drugs tested in this study show a correlation between animal and human studies in these specific circumstances. Further validation studies are needed to make these correlations clinical applicable.

Journal Article↗
PubMed2003

Internal and external factors affecting the development of neuropathic pain in rodents. Is it all about pain?

It is important to know the factors that will influence animal models of neuropathic pain. A good reproducibility and predictability in different strains of animals for a given test increases the clinical relevance and possible targeting. An obligatory requirement for enabling comparisons of results of different origin is a meticulous definition of the specific sensitivities of a model for neuropathic pain and a description of the test conditions. Factors influencing neuropathic pain behavior can be subdivided in external and internal factors. The most important external factors are; timing of the measurement of pain after induction of neuropathy, circadian rhythms, seasonal influences, air humidity, influence of order of testing, diet, social variables, housing and manipulation, cage density, sexual activity, external stress factors, and influences of the experimenter. The internal factors are related to the type of animal, its genetic background, gender, age, and the presence of homeostatic adaptation mechanisms to specific situations or stress. In practice, the behavioral presentations to pain depend on the combination of genetic and environmental factors such as accepted social behavior. It also depends on the use of genetic manipulation of the animals such as in transgenic animals. These make the interpretation of data even more difficult. Differences of pain behavior between in- and outbred animals will be better understood by using modern analysis techniques. Substrains of animals with a high likelihood for developing neuropathic pain make the unraveling of specific pathophysiological mechanisms possible. Concerning the effect of stress on pain, it is important to differentiate between external and internal stress such as social coping behavior. The individual dealing with this stress is species sensitive, and depends on the genotype and the social learning. In the future, histo-immunological and genetic analysis will highlight similarities of the different pathophysiological mechanisms of pain between different species and human subjects. The final objective for the study of pain is to describe the genetics of the eliciting pain mechanisms in humans and to look for correlations with the knowledge from basic research. Therefore, it is necessary to know the genetic evolution of the different mechanisms in chronic pain. In order to be able to control the clinical predictability of a putative treatment the evolutionary pharmacogenomic structure of specific transmitters and receptors must be clarified.

Journal Article↗
PubMed2003

Opioid tolerance and dependence: an inevitable consequence of chronic treatment?

Although opioids provide effective analgesia, largely unsubstantiated concerns about opioid-induced tolerance, physical dependence and addiction have limited their appropriate use. As a consequence, many patients receive inadequate treatment for both malignant and non-malignant pain. However, it has been shown that analgesic tolerance develops less frequently during chronic opioid administration in a clinical context than in animal experiments, and that instituting an appropriate dosing regimen can minimise withdrawal symptoms. Early studies had suggested that addiction might result from chronic opioid therapy, though more recent data indicate a low risk in patients with no history of drug abuse. New treatment regimens may also reduce the risk of tolerance, physical dependence and addiction. Long-acting preparations, such as transdermal fentanyl and possibly some forms of other slow release opioids, which maintain constant opioid concentrations in the plasma, minimise the occurrence of the 'between-dose' symptoms such as withdrawal and opioid-induced euphoria. This review discusses the development of tolerance, physical dependence and addiction during opioid therapy, and the influence of these factors on the choice of treatment.

Analgesics, Opioid↗
PubMed2002

Role of 5-HT(2) receptors in the tryptamine-induced 5-HT syndrome in rats.

We distinguished the functions of the different 5-hydroxytryptamine-2 (5-HT(2)) receptor (5-HT(2)R) subtypes in the tryptamine-induced 5-HT syndrome in rats using (1) the 5-HT(2A)R antagonist R93274 (N-[(3-p-fluorophenyl-1-propyl)-4-methyl-4-piperidinyl]-4-amino-5-iodo-2-methoxybenzamide), the 5-HT(2A/C)R antagonist R99647 (2-(dimethylaminomethyl)2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine), the 5-HT(2B/C)R antagonist SB-242084 (6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline), and several 5-HT(2)R antagonists (ketanserin, risperidone, pipamperone and mianserin); and (2) chronic 5-HT(2)R activation by 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). In contrast to SB-242084, the selective 5-HT(2A)R antagonist R93274 as well as the non-selective 5-HT(2A)R antagonists (R99647, ketanserin, risperidone, pipamperone and mianserin) significantly inhibited tryptamine-induced forepaw treading and tremors, and reversed peripherally mediated cyanosis into hyperaemia; only the 5-HT(2A/C)R antagonists R99647 and mianserin inhibited the tryptamine-induced hunched back. Intermittent DOM administration (intravenously every 48 h for 12 days) did not change the centrally mediated tryptamine-induced forepaw treading, tremors and hunched back at 1, 4 or 7 days after the last DOM pretreatment. The DOM-induced head twitch response, measured immediately after every DOM injection, was not affected. In contrast, peripherally mediated cyanosis was reversed into hyperaemia in 75, 11 and 20% of all pretreated rats at 1, 4 and 7 days, respectively, after the last DOM administration. Taken together, these finding suggest that central 5-HT(2A)Rs mediate tryptamine-induced forepaw treading and tremors, that peripheral 5-HT Rs mediate tryptamine-induced cyanosis, and that 5-HT(2A)Rs mediate tryptamine-induced hunched back. Peripheral 5-HT(2C)Rs are more sensitive to desensitization after intermittent treatment with an agonist than central 5-HT(2A)Rs.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed2001

Probing opioid receptor-ligand interactions by employment of indolizidin-9-one amino acid as a constrained Gly(2)-Gly(3) surrogate in a leucine-enkephalin mimic.

The relationship between the conformation and biological activity of Leu-enkephalin was studied using (2S,6R,8S)-9-oxo-8-N-(Boc)amino-1-azabicyclo[4.3.0]nonane-2-carboxylic acid [(2S,6R,8S)-1, I(9)AA] as a constrained Gly(2)-Gly(3) dipeptide surrogate. [I(9)AA](2,3)-Leu-enkephalin 12 was assembled using solid-phase peptide synthesis on Merrifield resin with TBTU as the coupling reagent. The in vitro assays indicated that [I(9)AA](2,3)-Leu-enkephalin 12 exhibited affinities for the mu- and delta-opioid receptors that were three orders of magnitude lower than that of Leu-enkephalin, as well as partial agonist character for both receptors. In in vivo assays for spinal analgesia, the indolizidinone analog 12 showed significantly enhanced duration of action, indicating an increased metabolic stability. Conformational analysis was performed using NMR and CD spectroscopy. The amide temperature coefficients and 3J(NH-CalphaH) coupling constants for 12 could not support a hydrogen-bonded beta-turn structure; however, its CD spectrum indicated a turn conformation. Incorporation of indolizidinone amino acid 1 into Leu-enkephalin thus provided additional support for the importance of a turn conformation for the biological activity of the native peptide.

Amino Acids↗
PubMed1998

Comparison of the analgesic and intestinal effects of fentanyl and morphine in rats.

Clinical studies report a low incidence of intestinal side effects with transdermally administered fentanyl (TTS-fentanyl) in comparison with oral morphine. To support these clinical data, analgesic and intestinal effects of both opioids were compared in rats. After subcutaneous injection, analgesia in the tail withdrawal reaction test was obtained at a peak effect dose of 0.032 mg/kg with fentanyl and 8.0 mg/kg with morphine. This analgesic dose exceeded the ED50 for inhibition of castor oil-induced diarrhea only slightly (1.1 x) in the case of fentanyl (0.028 mg/kg) but markedly (36 x) in the case of morphine (0.22 mg/kg). To reverse completely the antidiarrheal effect of equivalent analgesic doses of the opioids (their ED50S for analgesia lasting 2 hours), much more naloxone was required in the case of morphine (5.4 mg/kg) than in the case of fentanyl (0.19 mg/kg). After oral administration, the difference between both opioids was less pronounced. Analgesia was obtained at 0.85 mg/kg with fentanyl and 32 mg/kg with morphine. This analgesic dose only slightly (1.7 x) exceeded the antidiarrheal dose in the case of fentanyl (0.49 mg/kg) but significantly (6.2 x) in the case of morphine (5.2 mg/ kg). To reverse completely the antidiarrheal effect of equivalent analgesic oral doses of the opioids (their ED50S for analgesia lasting 2 hours), more naloxone was required in the case of morphine (11 mg/kg) than in the case of fentanyl (2.0 mg/kg). Rapid penetration of fentanyl into the brain is thought to be responsible for small dissociation between the analgesic and intestinal effect of this lipophilic opioid. The present data provide preclinical evidence to support the relatively low incidence of intestinal side effects observed clinically with the use of TTS-fentanyl in comparison with orally administered morphine.

Analgesics, Opioid↗
PubMed1992

Spinal sufentanil in rats: Part III: Effect of diluent volume on epidural sufentanil.

Male Wistar rats were injected epidurally with various doses of sufentanil in 3 different dilution volumes, in order to determine differences in the lowest ED50 values for analgesia and side-effects. The lowest ED50 for both a TWR latency greater than 6 and greater than or equal to 10 s was significantly lower in the 20-microliters group as compared to the 2-microliters group. With an injection of 5 microliters, intermediate values were obtained. With regard to the side-effects, there was a trend towards increased systemic resorption with larger diluent volumes in spite of a better and more selective spinal effect, as evidenced by increasing specificity ratios. In terms of duration of analgesia at fixed doses of sufentanil, different results were obtained. At low doses of sufentanil, a pronounced diluent volume effect was present and the duration of analgesia increased as a function of the volume. At higher doses of sufentanil, however, the volume effect faded away and no differences were observed as a function of the diluent.

Analgesia, Epidural↗
PubMed1990

Comparison of epidural sufentanil plus clonidine with sufentanil alone for postoperative pain relief.

Sufentanil 25 micrograms plus clonidine 1 microgram/kg administered epidurally was compared with epidural sufentanil 50 micrograms alone in a double-blind fashion for pain relief in 40 patients after abdominal surgery. The duration of complete pain relief was significantly longer in those who received the mixture. Oxygen saturation was reduced 10 and 20 minutes after sufentanil alone, but remained stable after sufentanil and clonidine. There were significant decreases in arterial blood pressure in the latter group that were maximum between 20 and 120 minutes after administration.

Adult↗
PubMed1982

Further evidence validating adjuvant arthritis as an experimental model of chronic pain in the rat.

The experiments described here were aimed at further validating adjuvant arthritis as an animal model of chronic pain. It was found that the relative oral intake of a 0.008 mg/ml solution of fentanyl was higher in arthritic than in normal control rats; this difference was predicted by the notion that the analgesic effect of a substance may reinforce its intake in animals exposed to pain, more so than in normal pain-free animals. It was also found that body weight decreases and that vocalizations of aggregated rats increase as a result of the challenge; these effects suggest that the vegetative signs and the behavioral irritability which are characteristic of chronic pain in humans, also occur in arthritic animals. The pain which thus seems to be associated with adjuvant arthritis was estimated to have its onset on days 10-11, to peak on days 18-21, and to terminate on days 35-40 after inoculation with Mycobacterium butyricum.

Animals↗
PubMed1982

Parametric effects in the discrimination of intracranial stimulation: some methodological and analytical issues.

Rats were implanted with electrodes in the medial forebrain bundle at the level of the lateral hypothalamus. Electrical stimulation was established as a conditioned stimulus for responding in a modified two-way active shock avoidance procedure. Stimulus generalization experiments were conducted to determine the effects of pulse frequency, current intensity, pulse duration, and of train duration. It was found that the discriminative stimulus properties of the electrical stimulation co-varied in an orderly manner with variations in each of the parameters. The generalization data sets of frequency, intensity, and train duration could be fitted by linear functions in log-linear coordinates; the effects of pulse duration generated a biphasic gradient. An analysis in terms of charge revealed that train duration had the lowest slope, whereas frequency and intensity generated equally steep functions. The most striking differences occurred among conditions which were similar in terms of current intensity, pulse duration and number of pulses, but which differed in the temporal patterning of pulses. Some methodological and analytical aspects of discrimination and generalization with intracranial stimulation are discussed.

Animals↗