14 results on '"Martin Koltzenburg"'
Search Results
2. Functional imaging in microfluidic chambers reveals sensory neuron sensitivity is differentially regulated between neuronal regions
- Author
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Erik Årstad, Alex J. Clark, Martin Koltzenburg, Mona AlQatari, Guillermo Menendez, Niral Patel, and Giampietro Schiavo
- Subjects
0301 basic medicine ,Sensory Receptor Cells ,Action potential ,Microfluidics ,Action Potentials ,Sensory system ,Biology ,Stimulus (physiology) ,03 medical and health sciences ,Calcium imaging ,Ganglia, Spinal ,medicine ,Animals ,Sodium channel ,Electric Stimulation ,Sensory neuron ,Rats ,030104 developmental biology ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,nervous system ,Neurology ,Calcium ,Neurology (clinical) ,Transduction (physiology) ,Free nerve ending ,Neuroscience - Abstract
Primary afferent sensory neurons are incredibly long cells, often traversing distances of over 1 m in humans. Cutaneous sensory stimuli are transduced in the periphery by specialised end organs or free nerve endings, which code the stimulus into electrical action potentials that propagate towards the central nervous system. Despite significant advances in our knowledge of sensory neuron physiology and ion channel expression, many commonly used techniques fail to accurately model the primary afferent neuron in its entirety. In vitro experiments often focus on the cell somata and neglect the fundamental processes of peripheral stimulus transduction and action potential propagation. Despite this, these experiments are commonly used as a model for cellular investigations of the receptive terminals. We demonstrate that ratiometric calcium imaging performed in compartmentalised sensory neuron cultures can be used to directly and accurately compare the sensitivity and functional protein expression of isolated neuronal regions in vitro. Using microfluidic chambers, we demonstrate that the nerve terminals of cultured dorsal root ganglion neurons can be depolarised to induce action potential propagation, which has both tetrodotoxin-resistant and tetrodotoxin-sensitive components. Furthermore, we show that there is a differential regulation of proton sensitivity between the sensory terminals and somata in cultured sensory neurons. We also demonstrate that capsaicin sensitivity is highly dependent on embryonic dissection age. This approach enables a comprehensive method to study the excitability and regional sensitivity of cultured sensory neurons on a single-cell level. Examination of the sensory terminals is crucial to further understand the properties and diversity of dorsal root ganglion sensory neurons.
- Published
- 2018
3. Imaging of peripheral nerve lesions
- Author
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Martin Bendszus and Martin Koltzenburg
- Subjects
Pathology ,medicine.medical_specialty ,Wallerian degeneration ,Electromyography ,medicine ,Humans ,Peripheral Nerves ,Muscle, Skeletal ,Carpal tunnel syndrome ,medicine.diagnostic_test ,business.industry ,Magnetic resonance neurography ,Peripheral Nervous System Diseases ,Skeletal muscle ,Magnetic resonance imaging ,Anatomy ,medicine.disease ,Magnetic Resonance Imaging ,Muscle Denervation ,Muscle atrophy ,medicine.anatomical_structure ,Neurology ,Neurology (clinical) ,Sciatic nerve ,medicine.symptom ,business - Abstract
Clinical investigations of peripheral nerve lesions routinely involve nerve conduction studies and electromyography. Imaging studies are often used to exclude focal mass lesions or external compression and to visualize muscle atrophy. More recently, it has been recognized that magnetic resonance imaging can identify changes in peripheral nerves and secondary neurogenic alterations in skeletal muscle, which may significantly enhance its use in the differential diagnosis of peripheral nerve disease.Acute axonal nerve lesions cause a hyperintense signal on T2-weighted images at and distal to the lesion site, which correlates with Wallerian degeneration and nerve oedema. Superparamagnetic iron oxide particles provide an exciting new tool to detect the invasion of macrophages into the degenerating nerve distal to an axonal lesion. Prolongation of the T2 relaxation time and gadolinium enhancement of denervated muscle develop in parallel to the development of spontaneous activity on electromyography, and are probably the consequence of capillary enlargement and increased muscular blood volume.Magnetic resonance imaging supplements the differential diagnosis of peripheral nerve disease. An advantage over clinical neurophysiological investigations is that it is operator independent and painless. It can identify axonal damage and may thus help to identify a lesion site precisely, where fractionated nerve conduction studies are not applicable. Novel contrast media may potentially be used to detect pathophysiologically relevant mechanisms such as infiltration of the nerve by macrophages. Magnetic resonance imaging also has the advantage of providing a lasting detailed topographical picture of regional variations and avoids localization errors of muscles in electromyography.
- Published
- 2004
4. The functional expression of mu opioid receptors on sensory neurons is developmentally regulated; morphine analgesia is less selective in the neonate
- Author
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Richard F. Howard, Maria Fitzgerald, Reema Nandi, Daniel Beacham, Martin Koltzenburg, and Jacqueta Middleton
- Subjects
Male ,medicine.medical_specialty ,Hot Temperature ,medicine.drug_class ,Receptors, Opioid, mu ,Stimulation ,Rats, Sprague-Dawley ,Dorsal root ganglion ,Opioid receptor ,Ganglia, Spinal ,Internal medicine ,Animals ,Medicine ,Neurons, Afferent ,Morphine ,business.industry ,Age Factors ,Sensory neuron ,Rats ,Analgesics, Opioid ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,Nociception ,Endocrinology ,Animals, Newborn ,nervous system ,Neurology ,Opioid ,Sensory Thresholds ,Calcium ,Female ,Neurology (clinical) ,μ-opioid receptor ,business ,Neuroscience ,medicine.drug - Abstract
Opioid requirements in neonatal patients are reported to be lower than older infants and this may be a reflection of the developmental regulation of opioid receptors. In this study we have investigated the postnatal regulation of Mu opioid receptor (MOR) function in both rat lumbar dorsal root ganglion (DRG) cultures and behavioural mechanical and thermal reflex tests in rat pups. Immunostaining with MOR and selective neurofilament (NF200) antibodies was combined with calcium imaging of MOR function in cultured neonatal and adult rat dorsal root ganglion cells. Calcium imaging showed that a significantly greater number of neonatal DRG neurons expressed functional MOR compared to adult (56.5+/-3.4 versus 39.9+/-1.5%, n=8, mean+/-SEM, P0.001). This expression is confined to the large, neurofilament positive sensory neurons, while expression in small, nociceptive, neurofilament negative neurons remains unchanged. Sensory threshold testing in rat pups showed that the analgesic potency of systemic morphine to mechanical stimulation is significantly greater in the neonate and declines with postnatal age. Morphine analgesic potency in thermal nociceptive tests did not change with postnatal age. These experiments show that the MOR expressed on large DRG neurons in neonates are functional and are subject to postnatal developmental regulation. This changing functional receptor profile is consistent with greater morphine potency in mechanical, but not thermal, sensory tests in young animals. These results have important clinical implications for the use of morphine in neonates and provide a possible explanation for the differences in morphine requirements observed in the youngest patients.
- Published
- 2004
5. Complex Regional Pain Syndromes: Guidelines for Therapy
- Author
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Martin Koltzenburg, Michael Stanton-Hicks, Roberg Wilder, Torsten Gordh, Norman Harden, Ralf Baron, Nelson Hendler, Prithvi Raj, and Robert A. Boas
- Subjects
Biopsychosocial model ,Causalgia ,medicine.medical_specialty ,Palliative care ,medicine.medical_treatment ,Pain ,Physical medicine and rehabilitation ,medicine ,Humans ,Pain Management ,Behavior management ,Rehabilitation ,Modalities ,business.industry ,Palliative Care ,Syndrome ,medicine.disease ,Neuromodulation (medicine) ,Reflex Sympathetic Dystrophy ,Anesthesiology and Pain Medicine ,Complex regional pain syndrome ,Practice Guidelines as Topic ,Musculoskeletal injury ,Physical therapy ,Neurology (clinical) ,business ,Algorithms - Abstract
This report aims to present an orderly approach to the treatment of Chronic Regional Pain Syndrome (CRPS) types I and II through an algorithm. The central theme is functional restoration: a coordinated but progressive approach that introduces each of the treatment modalities needed to achieve both remission and rehabilitation. Reaching objective and measurable rehabilitation goals is an essential element. Specific exercise therapy to reestablish function after musculoskeletal injury is central to this functional restoration. Its application to CRPS is more contingent on varying rates of progress that characterize the restoration of function in patients with CRPS. Also, the various modalities that may be used, including analgesia by pharmacologic means or regional anesthesia or the use of neuromodulation, behavioral management, and the qualitatively different approaches that are unique to the management of children with CRPS, are provided only to facilitate functional improvement in a stepwise but methodical manner. Patients with CRPS need an individual approach that requires extreme flexibility. This distinguishes the management of these conditions from other well-described medical conditions having a known pathophysiology. In particular, the special biopsychosocial factors that are critical to achieving a successful outcome are emphasized. This algorithm is a departure from the contemporary heterogeneous approach to treatment of patients with CRPS. The underlying principles are motivation, mobilization, and desensitization facilitated by the relief of pain and the use of pharmacologic and interventional procedures to treat specific signs and symptoms. Self-management techniques are emphasized, and functional rehabilitation is the key to the success of this algorithm.
- Published
- 1998
6. Peripheral administration of nerve growth factor in the adult rat produces a thermal hyperalgesia that requires the presence of sympathetic post-ganglionic neurones
- Author
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Stephen B. McMahon, Nicholai Yu. Andreev, Martin Koltzenburg, and Natalia Dimitrieva
- Subjects
medicine.medical_specialty ,Sympathetic nervous system ,Hot Temperature ,Injections, Intradermal ,Sympathetic Fibers, Postganglionic ,Internal medicine ,Animals ,Humans ,Medicine ,Nerve Growth Factors ,Sympathectomy ,Guanethidine ,Neurons ,biology ,business.industry ,Recombinant Proteins ,Rats ,Anesthesiology and Pain Medicine ,Nerve growth factor ,Nociception ,Endocrinology ,medicine.anatomical_structure ,nervous system ,Neurology ,Hyperalgesia ,Anesthesia ,biology.protein ,Nociceptor ,Neurology (clinical) ,medicine.symptom ,Licking ,business ,medicine.drug ,Neurotrophin - Abstract
Previous evidence suggests that, in adult animals, nerve growth factor (NGF) can induce hyperalgesia, and may be an endogenous mediator in some persistent pain states. Here we have studied the effects of single intradermal injections of 50-500 ng of human recombinant NGF into the plantar skin of adult rat hindpaws. We found that doses of 250 ng and more produced a prolonged and stable thermal hyperalgesia to radiant heat. NGF did not produce overt pain behaviour as judged by the absence of paw licking or guarding of the injected paw. In animals subjected to surgical or chemical sympathectomy, by repeated systemic guanethidine treatments, the hyperalgesic effects of NGF were markedly reduced. We also found that NGF produced plasma extravasation in rat skin, using the Evan's blue method, with a dose dependency similar to that determined for hyperalgesia. Together, these findings suggest that NGF can lead to a rapid activation and sensitization of cutaneous nociceptors. However, these actions appear at least partly indirect, requiring the presence of normal sympathetic post-ganglionic terminals.
- Published
- 1995
7. Circulating adhesion molecules and inflammatory mediators in demyelination: A review
- Author
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Juan J. Archelos, K.V. Toyka, Martin Koltzenburg, Hans-Peter Hartung, Karlheinz Reiners, Ralf Gold, and Jürgen Zielasek
- Subjects
Encephalomyelitis, Autoimmune, Experimental ,Multiple Sclerosis ,Microglia ,biology ,Cell adhesion molecule ,T-Lymphocytes ,Polyradiculoneuropathy ,Complement System Proteins ,Blood–brain barrier ,Myelin basic protein ,Myelin ,medicine.anatomical_structure ,Immune system ,Immunology ,medicine ,biology.protein ,Cytokines ,Humans ,Tumor necrosis factor alpha ,Neurology (clinical) ,Inflammation Mediators ,Cell Adhesion Molecules ,Neuroinflammation ,Demyelinating Diseases - Abstract
Accumulating evidence shows that adhesion molecules are critically involved in inflammatory demyelination in the focusing of systemic immune responses into the target tissue, the nervous system.Adhesion molecules are upregulated through the action of cytokines. Tumor necrosis factor alpha appears to be of prime importance. Circulating adhesion molecules probably reflect acute inflammatory episodes in the central and peripheral nervous system, but may also function to modulate ongoing inflammatory responses. Cytokines released by T H 1 cells render resident and immigrant macrophages, as well as microglia, activated to synthesize and release increased amounts of inflammatory mediators, such as oxygen radicals, nitric oxide metabolites, and components of the complement system. A more detailed understanding of the sequence of immunopathologic events that culminate in myelin damage in the central and peripheral nervous systems has revealed several sites to which more specific and effective immunointervention can be targeted. NEUROLOGY 1995;45(Suppl 6): S22-S32
- Published
- 1995
8. Painful vascular compression syndrome of the sciatic nerve caused by gluteal varicosities
- Author
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Jose Perez, Karlheinz Reiners, Martin Bendszus, Peter Rieckmann, Martin Koltzenburg, and Laszlo Solymosi
- Subjects
Male ,medicine.medical_specialty ,Decompression ,Provocation test ,Sitting ,Varicose Veins ,medicine ,Humans ,Aged ,Sciatica ,medicine.diagnostic_test ,business.industry ,Vascular disease ,Nerve Compression Syndromes ,Magnetic resonance imaging ,Buttock Pain ,medicine.disease ,Magnetic Resonance Imaging ,Surgery ,body regions ,nervous system ,Buttocks ,Female ,Neurology (clinical) ,Sciatic nerve ,Sciatic Neuropathy ,medicine.symptom ,business - Abstract
The authors report three patients with chronic sciatic pain without focal neurologic deficit. Sitting or lying on the affected side provoked pain, and standing and walking relieved it. MRI revealed varicotic gluteal vessels compressing the sciatic nerve. Decompression of the nerve resulted in complete and permanent pain relief. Sciatic or buttock pain in patients with varicosities and pain provocation in the sitting or lying position suggests this neurovascular compression syndrome.
- Published
- 2003
9. Peroneal nerve palsy caused by thrombosis of crural veins
- Author
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Martin Koltzenburg, Jose Perez, Laszlo Solymosi, Martin Bendszus, and Karlheinz Reiners
- Subjects
Male ,medicine.medical_specialty ,Neural Conduction ,Electromyography ,Veins ,Paralysis ,Humans ,Medicine ,Peroneal Neuropathies ,Vein ,Aged ,Venous Thrombosis ,Leg ,medicine.diagnostic_test ,business.industry ,Vascular disease ,medicine.disease ,Thrombosis ,Surgery ,Paresis ,Venous thrombosis ,Peroneal nerve palsy ,medicine.anatomical_structure ,Acute Disease ,Etiology ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Acute palsies of the peroneal nerve may have a variety of causes. In many patients, the cause remains undetermined. The authors report a patient with a thrombosis of a crural vein causing an acute peroneal nerve palsy. If the clinical history of patients with an acute peroneal nerve lesion is suggestive of venous thrombosis an appropriate diagnostic workup should be considered.
- Published
- 2002
10. Dynamic and static components of mechanical hyperalgesia in human hairy skin
- Author
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Martin Koltzenburg, Lars E.R. Lundberg, and H.Erik Torebjörk
- Subjects
Adult ,Male ,Pain Threshold ,Hot Temperature ,Pain ,Stimulation ,Nerve Fibers, Myelinated ,chemistry.chemical_compound ,Physical Stimulation ,Pressure ,medicine ,Humans ,Plant Oils ,Radial nerve ,Skin ,Burning Pain ,Plant Extracts ,business.industry ,Nociceptors ,Middle Aged ,Anesthesiology and Pain Medicine ,Nociception ,Allodynia ,Neurology ,chemistry ,Capsaicin ,Anesthesia ,Hyperalgesia ,Neuropathic pain ,Irritants ,Female ,Radial Nerve ,Neurology (clinical) ,medicine.symptom ,Skin Temperature ,business ,Hair ,Mustard Plant - Abstract
The principle finding of the present study is that there are two types of mechanical hyperalgesia developing in human hairy skin following injurious stimuli. Mechanical hyperalgesia comprises a dynamic component (brush-evoked pain, allodynia) signalled by large myelinated afferents and a static component (hyperalgesia to pressure stimuli) signalled by unmyelinated afferents. While the static component is only found in the injured area, the dynamic component also extends into a halo of undamaged tissue surrounding the injury. The irritant chemicals, mustard oil or capsaicin, were applied transdermally in 20 subjects to a patch (2 x 2 cm) of hairy skin. Both substances evoked burning pain and hyperalgesia to mechanical stimuli. While stroking normal skin with a cotton bud was perceived only as touch prior to chemical stimulation, there was a distinctly unpleasant sensation afterwards. This component of mechanical hyperalgesia persisted for at least 30 min and was present in the skin exposed to the irritants (primary hyperalgesia) as well as in a zone of untreated skin surrounding the injury (secondary hyperalgesia) measuring 38 +/- 4 cm2 after capsaicin. Pressure pain thresholds dropped to 55 +/- 8% of baseline level after mustard oil and to 46 +/- 9% after capsaicin. However, this drop of thresholds was short-lived, lasting 5 min following mustard oil but persisting more than 30 min following capsaicin treatment. The reduction of pressure pain thresholds was only observed for treated skin areas, but not in the surrounding undamaged tissue from where brush-evoked pain could be evoked. When pressure pain thresholds were lowered, the pain had a burning quality which differed distinctly from the quality of brush-evoked pain. On-going burning pain and both types of mechanical hyperalgesia were critically temperature dependent. Mildly cooling the skin provided instant relief from on-going pain, abolished brush-evoked pain and normalized pressure pain thresholds. Rewarming resulted in a reappearance of on-going pain and hyperalgesia. The effect of a nerve compression block of the superficial radial nerve on these sensations was tested in 14 experiments. When the ability to perceive light touch had been abolished, there was also no touch-evoked pain, indicating that this component of mechanical hyperalgesia is mediated by large-diameter primary afferents. At a later stage of the block when the subjects' ability to perceive cold stimuli had also been lost, application of cool stimuli still eliminated on-going burning pain, suggesting that pain relief afforded by cooling the skin acts at the peripheral receptor level and not by central masking.(ABSTRACT TRUNCATED AT 400 WORDS)
- Published
- 1992
11. A novel technique for the evaluation of mechanical pain and hyperalgesia
- Author
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Lothar U.E. Kohllöffel, Hermann O. Handwerker, and Martin Koltzenburg
- Subjects
Adult ,Male ,Time Factors ,Pain ,Stimulation ,Stimulus (physiology) ,Sensation ,medicine ,Psychophysics ,Humans ,Pain Measurement ,Skin ,Reproducibility ,business.industry ,Middle Aged ,Anesthesiology and Pain Medicine ,Neurology ,Hyperalgesia ,Sensory Thresholds ,Anesthesia ,Reflex ,Nociceptor ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Biomedical engineering - Abstract
We describe a new technique which is useful for the evaluation of mechanically induced pain and hyperalgesia. Light metal cylinders are guided and accelerated in a barrel. On impact against the skin they elicit a brief sensation of pain. This method allows the application of a wide range of controllable innocuous and noxious impact velocities of the cylinder at variable stimulus repetition rates. The system is sufficiently flexible to stimulate perpendicularly any skin area and to move rapidly to adjacent target regions if desired. Psychophysical testing using magnitude estimation techniques revealed that pain thresholds were normally distributed. Over a wide range of stimulation intensities monotonically increasing stimulus response functions were obtained. Repeated testing showed a good intra-individual reproducibility of both threshold and supramaximal pain ratings. The method was also useful in determining the time course of pain and mechanical hyperalgesia following a brief painful stimulus. We conclude that the new technique is useful for evaluating psychophysical stimulus response functions of mechanically induced pain and its changes following tissue injury. This technique may also hold some promise in quantifying altered pain sensitivity in patients.
- Published
- 1991
12. Towards a mechanism-based classification of pain?
- Author
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Clifford J. Woolf, Bruce L. Kidd, Eric Torebjork, Richard B. Lipton, Richard Payne, Ronald Dubner, John D. Loeser, Martin Koltzenburg, Michael Doherty, and Gary J. Bennett
- Subjects
Anesthesiology and Pain Medicine ,Text mining ,Neurology ,business.industry ,MEDLINE ,Mechanism based ,Medicine ,Neurology (clinical) ,Artificial intelligence ,business ,computer.software_genre ,computer ,Natural language processing - Published
- 1998
13. Sympathetic reflex activity and neuroeffector transmission change after chronic nerve lesions
- Author
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Martin Koltzenburg and Wilfrid Jänig
- Subjects
medicine.medical_specialty ,Anesthesiology and Pain Medicine ,Neurology ,business.industry ,Internal medicine ,medicine ,Cardiology ,Neurology (clinical) ,Neuroeffector transmission ,business ,Sympathetic reflex - Published
- 1990
14. Properties of mechano- and chemosensitive primary afferents from urinary bladder
- Author
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N. Lobenberg-Khosravi, Martin Koltzenburg, Heinz-Joachim Häbler, E. Bahns, and Wilfrid Jänig
- Subjects
medicine.medical_specialty ,Anesthesiology and Pain Medicine ,Primary (chemistry) ,Urinary bladder ,medicine.anatomical_structure ,Neurology ,business.industry ,medicine ,Urology ,Neurology (clinical) ,business - Published
- 1987
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