Lege Artis Medicinae



NOVEMBER 20, 2007

Lege Artis Medicinae - 2007;17(11)

[The use of opioids to relieve strong, unbearable pain is a method that has been known for thousands of years and is still effective today. In contrast to the earlier view, opioids today are not only given to cancer patients. The application area of morphine derivatives is generally the relief of exceptionally strong pain regardless of the diagnosis, but opiates are undoubtedly most commonly used to treat cancer-related or strong acute pain. Strong pain reducers are used much more in developed countries for the treatment of non-cancer related severe pain refractory to other approaches. Today the use of opiates and their derivatives (fentanyl, oxycodon) for non-cancer related pain relief is recognized by the national health insurance in that it allows general practitioners to prescribe them, upon the recommendation of a neurosurgeon, orthopaedic surgeon, traumatologist or rheumatologist, with a significant 90% subsidy for six months to ensure easy access for patients in severe, refractory pain due to degenerative musculoskelatal diseases (ICD: M47, M48, M16.9, M17.9, M54.4, M51.0, M51.1). The indications of opioid use, however, are not limited to strong nociceptive pain since they are also effective in certain types of peripheral neuropathic pain. In brief, a basic principle of the use of major analgetics is that their indication is primarily based on the intensity of pain and not on the nature of the disease, even though the latter has a major influence on the clinician's strategy of pain relief.]



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REUSZ György, SZABÓ J. Attila

[Erythropoiesis stimulating agents are glycoproteins in which the oligosaccharide chains that terminate in sialic acid bind to the peptide with glycosidic bond. The lower the sialic acid content of the erythropoietin, the higher its receptor affinity, while its half-life in the circulation decreases. The biological effect depends on the balance of these factors. In the third-generation erythropoiesis stimulating molecule CERA (continuous erythropoietin receptor activator) a large polyethylene glycol molecule is substituted for sialic acid to ensure slow elimination and better biological efficiency. During treatment with erythropoiesis stimulating agents, haemoglobin levels show cyclic fluctuation. This cyclicity is undesirable, so its frequency and amplitude should be reduced as much as possible. The most recent results suggest that CERA may reduce haemoglobin cyclicity.]

Lege Artis Medicinae

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All articles in the issue

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Clinical Neuroscience

[Antinociceptive effect of vinpocetine - a comprehensive survey]


[Blockade of retrograde transport of nerve growth factor (NGF) in a peripheral sensory nerve is known to induce transganglionic degenerative atrophy (TDA) of central sensory terminals in the upper dorsal horn of the related, ipsilateral segments(s) of the spinal cord. The ensuing temporary blockade of transmission of nociceptive impulses has been utilized in the therapy of intractable pain, using transcutaneous iontophoresis of the microtubule inhibitors vincristin and vinblastin, drugs which inhibit retrograde transport of NGF. Since microtubule inhibition might inhibit (at least theoretically) mitotic processes in general, we sought to find a drug which inhibits retrograde transport of NGF without microtubule inhibition. Vinpocetine, a derivate of vincamine, which does not interfere with microtubular function, was found to inhibit retrograde axoplasmic transport of NGF in peripheral sensory nerves, similarly to vincristin and vinblastin. Blockade of NGF transport is followed by transganglionic degenerative atrophy in the segmentally related, ipsilateral superficial spinal dorsal horn, characterized by depletion of the marker enzymes of nociception, fluoride resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP) from the Rolando substance and by decrease of the pain-related neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) from lamina I-II-III. Based upon these findings, it has been suggested that vinpocetine may result in a locally restricted decrease of nociception. Herewith, the structural and behavioral effects of perineurally administered vinpocetine are discussed. Nociception, induced by intraplantar injection of formalin, was mitigated by perineural application of vinpocetine; also formalin-induced expression of c-fos in the ipsilateral, segmentally related superficial dorsal horn, was prevented by this treatment. Since vinpocetine is not a microtubule inhibitor, its mode of action is enigmatic. It is assumed that the effect of vinpocetine might be related to interaction with membrane-trafficking proteins, such as signalling endosomes and the endocytosis-mediating „pincher” protein, involved in retrograde axoplasmic transport of NGF, or to interaction with glial elements, recently reported to be involved in the modulation of pain in the spinal cord. Based on animal experiments it is assumed that the temporary, locally restricted decrease of nociception, induced by vinpocetine applied via transcutaneous iontophoresis, might open up new avenues in the clinical treatment of intractable pain.]

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[The paper describes the characteristics of limb pain associated with acute and chronic arterial occlusions, venous and lymphatic diseases, and underlines the importance of early diagnosis and treatment that may determine the fate of the limb. The type of leg ulcer developing as a complication of an arterial or venous disease can usually be diagnosed by the inspection of the leg. Symptoms that accompany venous thrombosis of the leg often pose serious differential diagnostic problems. The venous sinuses of the leg are of great clinical importance. Thromboses occurring in these are usually recognized late, thus adequate therapy is also started belatedly. Correct diagnosis determines the therapy to be chosen. The diseases of lymphatic vessels often produce tense leg pain by concomitant venous oedema. Peripheral arterial disease has been shown to be an independent risk factor of cardiovascular morbidity and mortality. In view of this, early recognition and adequate therapy of vascular changes in the lower limb may prevent its progression to a life-threatening vascular disease affecting the whole body. In humans, individual vascular diseases develop in various times and locations, but with a similar pathomechanism. Based on this rule, cerebral, cardiac and peripheral localisation of the vascular disease must be searched for in each patient. High professional standards and a uniform diagnostic thinking are key elements of success. This is promoted in the paper by a flow-chart indicating the steps to be taken by the GP in the management and care of patients with vascular disease.]

Lege Artis Medicinae

[Dangers of the use of performance enhancement drugs and food supplements]


[The history of humankind is full of stories related to performance enhancement drug abuse. For the purpose of improving explosive power and long-term physical performance central nervous system stimulating drugs and supplements, such as: amphetamine and cocaine have been used. Androgenic anabolic steroids are used for increasing skeletal muscle mass. The abuse of performance enhancer drugs is seriously deteriorating the human health, and have several negative side effects. Number of food-supplements - available in the market, often contain traces of steroids. So called designer steroids are extremely dangerous. In the near future it will be possible to enhance physical performance through genetic interventions.]

Lege Artis Medicinae

[Neuropathic pain: spotligth on amitriptyline]

FEHÉR Gergely, POHL Marietta, KAPUS Krisztián, GOMBOS Katalin, PUSCH Gabriella, MÁK Kornél, KOLTAI Katalin, BANK Gyula, KÓSA Gábor, VARJASI Gábor, TIBOLD Antal

[The management of neuropathic pain is a challenge both for patients and medical professioners. A novel approach is recommended for its management based on the novel neurobiological results of pain research. Multidisciplinary teams and medical consensus are required due to the variety of symptoms and concomittant psychopathology. This approach allows us to avoid extensive diagnostic and trerapeutic workups and appropiate treatment for our patients. Most extensive evidence is available for pharmacological treatment, and currently recommended first-line treatments include antidepressants (tricyclic agents and serotonin-norepinephrine reuptake inhibitors) and anticonvulsants (gabapentin and pregabalin). The aim of our review was to collect articles focusing on the efficacy of the most widely available and cheapest tricyclic agent, amitriptyline in different neuropathic pain conditions. ]

Clinical Neuroscience

[Antinociception by endogenous ligands at peripheral level]

HORVÁTH Gyöngyi, MÉCS László

[It is well known that a multitude of ligands and receptors are involved in the nociceptive system, and some of them increase, while others inhibit the pain sensation both peripherally and centrally. These substances, including neurotransmitters, neuromodulators, hormones, cytokines etc., may modify the activity of nerves involved in the pain pathways. It is also well known that the organism can express very effective antinociception in different circumstances, and during such situations the levels of various endogenous ligands change. Accordingly, a very exciting field of pain research relates to the roles of endogenous ligands. The peripheral action may possibly be extremely important, because low doses of the endogenous ligands may reduce pain without disphoric side-effects, and without the abused potential typical of centrally acting ligands. This review provides a comprehensive overview of the endogenous ligands that can induce antinociception, discusses their effects on different receptors and focuses on their action at peripheral level. We found 17 different endogenous ligands which produced antinociception after their topical administration. The results suggest an important direction for the development of pain strategies that focus on the local administrations of different endogenous ligands.]