9 results on '"Vrinten DH"'
Search Results
2. Sciatic nerve regeneration in mice and rats: recovery of sensory innervation is followed by a slowly retreating neuropathic pain-like syndrome.
- Author
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Vogelaar CF, Vrinten DH, Hoekman MF, Brakkee JH, Burbach JP, and Hamers FP
- Subjects
- Animals, Behavior, Animal, Functional Laterality physiology, Locomotion physiology, Mice, Mice, Inbred C57BL, Nerve Crush methods, Pain Measurement methods, Pain Threshold physiology, Rats, Rats, Wistar, Sciatic Nerve injuries, Time Factors, Walking physiology, Nerve Regeneration physiology, Recovery of Function, Sciatic Nerve physiopathology, Sciatic Neuropathy physiopathology
- Abstract
Peripheral nerve regeneration has been studied extensively in the sciatic nerve crush model, at the level of both function and gene expression. The crush injury allows full recovery of sensory and motor function in about 3 weeks as assessed by the foot reflex withdrawal test and De Medinacelli walking patterns. We used the recently developed CatWalk paradigm to study walking patterns in more detail in mice and rats. We found that, following the recovery of sensory function, the animals developed a state of mechanical allodynia, which retreated slowly over time. The motor function, although fully recovered with the conventional methods, was revealed to be still impaired because the animals did not put weight on their previously injured paw. The development of neuropathic pain following successful sensory recovery has not been described before in crush-lesioned animals and may provide an important new parameter to assess full sensory recovery.
- Published
- 2004
- Full Text
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3. Interaction between the spinal melanocortin and opioid systems in a rat model of neuropathic pain.
- Author
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Vrinten DH, Gispen WH, Kalkman CJ, and Adan RA
- Subjects
- Analgesics, Opioid pharmacology, Animals, Drug Interactions, Male, Melanocyte-Stimulating Hormones pharmacology, Morphine pharmacology, Naloxone pharmacology, Narcotic Antagonists pharmacology, Physical Stimulation, Rats, Rats, Wistar, Receptor, Melanocortin, Type 4, Receptors, Corticotropin antagonists & inhibitors, Sensory Thresholds physiology, alpha-MSH pharmacology, Endorphins physiology, Melanocyte-Stimulating Hormones metabolism, Pain physiopathology, Spinal Cord metabolism, alpha-MSH analogs & derivatives
- Abstract
Background: The authors recently demonstrated that administration of the melanocortin-4 receptor antagonist SHU9119 decreased neuropathic pain symptoms in rats with a sciatic chronic constriction injury. The authors hypothesised that there is a balance between tonic pronociceptive effects of the spinal melanocortin system and tonic antinociceptive effects of the spinal opioid system. Therefore, they investigated a possible interaction between these two systems and tested whether opioid effectiveness could be increased through modulation of the spinal melanocortin system activity., Methods: In chronic constriction injury rats, melanocortin and opioid receptor ligands were administered through a lumbar spinal catheter, and their effects on mechanical allodynia were assessed by von Frey probing., Results: Naloxone (10-100 microg) dose-dependently increased allodynia (percent of maximum possible effect of -67 +/- 9%), which is in agreement with a tonic antinociceptive effect of the opioid system. SHU9119 decreased allodynia (percent of maximum possible effect of 60 +/- 13%), and this effect could be blocked by a low dose of naloxone (0.1 microg), which by itself had no effect on withdrawal thresholds. Morphine (1-10 microg) dose-dependently decreased allodynia (percent of maximum possible effect of 73 +/- 14% with the highest dose tested). When 0.5 microg SHU9119 (percent of maximum possible effect of 47 +/- 14%) was given 15 min before morphine, there was an additive antiallodynic effect of both compounds., Conclusions: Together, these data confirm that there is an interaction between the spinal melanocortin and opioid systems and that combined treatment with melanocortin-4 receptor antagonists and opioids might possibly contribute to the treatment of neuropathic pain.
- Published
- 2003
- Full Text
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4. 'CatWalk' automated quantitative gait analysis as a novel method to assess mechanical allodynia in the rat; a comparison with von Frey testing.
- Author
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Vrinten DH and Hamers FF
- Subjects
- Animals, Computer-Aided Design, Diagnosis, Differential, Disease Models, Animal, Male, Pain classification, Pain diagnosis, Pain Threshold, Physical Stimulation instrumentation, Physical Stimulation methods, Rats, Rats, Wistar, Sciatic Nerve pathology, Sciatic Nerve physiopathology, Sciatic Nerve surgery, Signal Detection, Psychological, Statistics as Topic, Extremities physiopathology, Gait physiology, Pain physiopathology, Pain Measurement
- Abstract
A characteristic symptom of neuropathic pain is mechanical allodynia. In animal models of neuropathic pain, mechanical allodynia is often assessed using von Frey filaments. Although the forces applied with these filaments are highly reproducible, there are various disadvantages of using this method. Testing paradigms and definitions of withdrawal threshold are not standardised. Moreover, measurements may be influenced by various conditions, such as ambient temperature, humidity, weight bearing of the limb and stress. We have therefore investigated another technique to assess mechanical allodynia, the 'CatWalk' automated quantitative gait analysis. With this computer-assisted method of locomotor analysis, it is possible to objectively and rapidly quantify several gait parameters, including duration of different phases of the step cycle and pressure applied during locomotion. We tested rats with a chronic constriction injury of the sciatic nerve, a model of neuropathic pain, both with von Frey filaments and the CatWalk method. We demonstrate that these rats minimise contact with the affected paw during locomotion, as demonstrated by a reduction in stance phase and pressure applied during stance. Moreover, these parameters show a high degree of correlation with mechanical withdrawal thresholds as determined by von Frey filaments. We therefore suggest that the CatWalk method might serve as an additional tool in the investigation of mechanical allodynia.
- Published
- 2003
- Full Text
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5. Discovery and in vivo evaluation of new melanocortin-4 receptor-selective peptides.
- Author
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Nijenhuis WA, Kruijtzer JA, Wanders N, Vrinten DH, Garner KM, Schaaper WM, Meloen RH, Gispen WH, Liskamp RM, and Adan RA
- Subjects
- Amino Acid Substitution, Animals, Behavior, Animal drug effects, Binding Sites, Binding, Competitive, Cell Line, Cell Line, Tumor, Cold Temperature, Dose-Response Relationship, Drug, Grooming drug effects, Humans, Inhibitory Concentration 50, Male, Oligopeptides chemical synthesis, Oligopeptides metabolism, Pain Measurement drug effects, Rats, Rats, Wistar, Receptor, Melanocortin, Type 4 metabolism, Receptors, Melanocortin antagonists & inhibitors, Receptors, Melanocortin metabolism, Time Factors, alpha-MSH metabolism, alpha-MSH pharmacology, Oligopeptides pharmacology, Receptor, Melanocortin, Type 4 antagonists & inhibitors
- Abstract
The melanocortin-4 receptor (MC4R) is involved in several physiological processes, including body weight regulation and grooming behaviour in rats. It has also been suggested that the MC4R mediates the effects of melanocortin ligands on neuropathic pain. Selective compounds are needed to study the exact role of the MC4R in these different processes. We describe here the development and evaluation of new melanocortin compounds that are selective for the MC4R as compared with the other centrally expressed receptors, MC3R and MC5R. First, a library of 18 peptides, in which a melanocortin-based sequence was systematically point-mutated, was screened for binding to and activity on the MC3R, MC4R and MC5R. Compound Ac-Nle-Gly-Lys-D-Phe-Arg-Trp-Gly-NH(2) (JK1) appeared to be the most selective MC4R compound, based on affinity. This compound is 90- and 110-fold selective for the MC4R as compared to the MC3R and MC5R, respectively. Subsequent modification of JK1 yielded compound Ac-Nle-Gly-Lys-D-Nal(2)-Arg-Trp-Gly-NH(2) (JK7)(,) a selective MC4R antagonist with 34-fold MC4R/MC3R and 109-fold MC4R/MC5R selectivity. The compounds were active in vivo as determined in a grooming assay and a model for neuropathic pain in rats. Intravenous (i.v.) injections suggested that they were able to pass the blood-brain barrier.The compounds identified here will be useful in further research on the physiological roles of the MC4R.
- Published
- 2003
- Full Text
- View/download PDF
6. Chronic blockade of melanocortin receptors alleviates allodynia in rats with neuropathic pain.
- Author
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Vrinten DH, Adan RA, Groen GJ, and Gispen WH
- Subjects
- Adrenergic alpha-Agonists pharmacology, Animals, Cold Temperature, Hot Temperature, Injections, Spinal, Male, Melanocyte-Stimulating Hormones pharmacology, Pain etiology, Pain physiopathology, Pain Threshold drug effects, Rats, Rats, Wistar, Reaction Time, Receptors, Corticotropin agonists, Receptors, Corticotropin antagonists & inhibitors, Receptors, Corticotropin physiology, Receptors, Melanocortin, Spinal Cord metabolism, alpha-MSH pharmacology, Pain Management, Receptors, Corticotropin drug effects, Sciatic Nerve injuries, alpha-MSH analogs & derivatives
- Abstract
Unlabelled: We investigated the involvement of the spinal cord melanocortin (MC) system in neuropathic pain. Because we recently demonstrated that MC receptor ligands acutely alter nociception in an animal model of neuropathic pain, in this study we tested whether chronic administration was also effective. We hypothesized that chronic blockade of the spinal MC system might decrease sensory abnormalities associated with this condition. The effects of the MC receptor antagonist SHU9119 (0.5 microg/d) and agonist MTII (0.1 microg/d) were evaluated in rats with a chronic constriction injury of the sciatic nerve. Drugs were continuously infused into the cisterna magna. Antinociceptive effects were measured with tests involving temperature (10 degrees C or 47.5 degrees C) or mechanical (von Frey) stimulation. The administration of MTII increased mechanical allodynia, whereas SHU9119 produced a profound cold and mechanical antiallodynia, altering responses to control levels. The antiallodynic effects of SHU9119 were very similar to those produced by the alpha(2)-adrenergic agonist tizanidine (50 microg/d). The effects of SHU9119 and MTII are most likely mediated through the MC4 receptor, because this is the only MC-receptor subtype present in the spinal cord. We conclude that the chronic administration of MC4-receptor antagonists might provide a promising tool in the treatment of neuropathic pain., Implications: In this study we demonstrated that continuous intrathecal infusion of the melanocortin-receptor antagonist SHU9119 reduces cold and mechanical allodynia in rats with a chronic constriction injury of the sciatic nerve, a lesion producing neuropathic pain.
- Published
- 2001
- Full Text
- View/download PDF
7. Neuropathic pain: a possible role for the melanocortin system?
- Author
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Vrinten DH, Kalkman CJ, Adan RA, and Gispen WH
- Subjects
- Animals, Humans, Mononeuropathies classification, Pain classification, Pain metabolism, Polyneuropathies classification, Receptors, Melanocortin, alpha-MSH metabolism, Mononeuropathies physiopathology, Pain physiopathology, Polyneuropathies physiopathology, Receptors, Corticotropin physiology, alpha-MSH physiology
- Abstract
In humans, damage to the nervous system can lead to a pain state referred to as neuropathic pain. Here, we give a short overview of the clinical picture and classification of neuropathic pain and highlight some of the currently known pathophysiological mechanisms involved, with special emphasis on neuropeptide plasticity. In this context, we discuss a specific group of neuropeptides, the melanocortins. These peptides have been demonstrated to play a role in nociception and to functionally interact with the opiate system. Recently, we demonstrated that spinal melanocortin receptors are upregulated in a rat model of neuropathic pain and that blockade of the melanocortin MC(4) receptor has anti-allodynic effects in this condition, suggesting that the melanocortin system plays a role in neuropathic pain. A natural agonist of melanocortin receptors is alpha-melanocyte-stimulating hormone (alpha-MSH), derived from the precursor molecule pro-opiomelanocortin (POMC). Cleavage of this precursor also yields beta-endorphin, which is co-released with alpha-MSH in nociception-associated areas of the spinal cord. We hypothesise that melanocortin receptor blockade attenuates a tonic influence of alpha-MSH on nociception, thus allowing the analgesic effects of beta-endorphin to develop, resulting in the alleviation of allodynia. In this way, treatment with melanocortin receptor antagonists might enhance opioid efficacy in neuropathic pain, which would be of great benefit in clinical practice.
- Published
- 2001
- Full Text
- View/download PDF
8. Antagonism of the melanocortin system reduces cold and mechanical allodynia in mononeuropathic rats.
- Author
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Vrinten DH, Gispen WH, Groen GJ, and Adan RA
- Subjects
- Animals, Autoradiography, Constriction, Dose-Response Relationship, Drug, Drug Synergism, Injections, Spinal, Ligands, Male, Melanocyte-Stimulating Hormones administration & dosage, Oligopeptides pharmacology, Pain Measurement drug effects, Physical Stimulation, Rats, Rats, Wistar, Reaction Time drug effects, Receptor, Melanocortin, Type 3, Receptor, Melanocortin, Type 4, Receptors, Corticotropin administration & dosage, Receptors, Corticotropin agonists, Receptors, Corticotropin metabolism, Receptors, Melanocortin, Sciatic Nerve physiology, Sciatic Nerve surgery, Sensory Thresholds drug effects, Spinal Cord drug effects, Spinal Cord metabolism, Cold Temperature, Hyperalgesia metabolism, Receptors, Corticotropin antagonists & inhibitors, Sciatic Neuropathy metabolism, alpha-MSH analogs & derivatives
- Abstract
The presence of both pro-opiomelanocortin-derived peptides and melanocortin (MC) receptors in nociception-associated areas in the spinal cord suggests that, at the spinal level, the MC system might be involved in nociceptive transmission. In the present study, we demonstrate that a chronic constriction injury (CCI) to the rat sciatic nerve, a lesion that produces neuropathic pain, results in changes in the spinal cord MC system, as shown by an increased binding of (125)I-NDP-MSH to the dorsal horn. Furthermore, we investigated whether intrathecal administration (in the cisterna magna) of selective MC receptor ligands can affect the mechanical and cold allodynia associated with the CCI. Mechanical and cold allodynia were assessed by measuring withdrawal responses of the affected limb to von Frey filaments and withdrawal latencies upon immersion in a 4.5 degrees C water bath, respectively. We show that treatment with the MC receptor antagonist SHU9119 has a profound anti-allodynic effect, suggesting that the endogenous MC system has a tonic effect on nociception. In contrast, administration of the MC4 receptor agonists MTII and d-Tyr-MTII primarily increases the sensitivity to mechanical and cold stimulation. No antinociceptive action was observed after administration of the selective MC3 receptor agonist Nle-gamma-MSH. Together, our data suggest that the spinal cord MC system is involved in neuropathic pain and that the effects of MC receptor ligands on the responses to painful stimuli are exerted through the MC4 receptor. In conclusion, antagonism of the spinal melanocortin system might provide a new approach in the treatment of neuropathic pain.
- Published
- 2000
9. Central diabetes insipidus and Cushing's syndrome due to ectopic ACTH production by disseminated small cell lung cancer: a case report.
- Author
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Castro Cabezas M, Vrinten DH, Burgers JA, and Croughs RJ
- Subjects
- ACTH Syndrome, Ectopic therapy, Carcinoma, Small Cell metabolism, Carcinoma, Small Cell therapy, Cushing Syndrome therapy, Humans, Lung Neoplasms metabolism, Lung Neoplasms therapy, Male, Middle Aged, Pituitary Neoplasms metabolism, Pituitary Neoplasms therapy, ACTH Syndrome, Ectopic complications, Carcinoma, Small Cell secondary, Cushing Syndrome etiology, Diabetes Insipidus etiology, Lung Neoplasms pathology, Pituitary Neoplasms secondary
- Abstract
The present case report describes the rare clinical presentation of diabetes insipidus in a patient with an ectopic ACTH syndrome (morning plasma cortisol 1.10 mumol/l, morning plasma ACTH 322 ng/l) due to disseminated small cell lung cancer including a metastasis in the posterior pituitary. The patient was treated by combination chemotherapy and at the same time received octreotide to control hypercortisolism and desmopressin (DDAVP) to control polyuria. Partial tumour remission was achieved resulting in decreased cortisol production and disappearance of the diabetes insipidus. Medical treatment could be discontinued. Several months later tumour regrowth occurred, with recurrence of hypercortisolism (mean morning plasma cortisol 0.74 mumol/l, mean morning plasma ACTH 112 ng/l) but without diabetes insipidus. Early treatment of hypercortisolism in patients with an ectopic ACTH syndrome and disseminated small cell lung cancer may prolong survival and improve the quality of life.
- Published
- 1998
- Full Text
- View/download PDF
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