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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The actions of exogenous and endogenous opioids are mediated by at least three different opioid receptors, called μ, κ, and δ. Recently, we have detected a new variant of the rat μ-opioid receptor, which we termed rMOR1B and which differs from rMOR1 (now also called rMOR1A) in the amino acid sequence at the C-terminus. Both isoforms were proposed to be splicing variants of the same gene. To elucidate the molecular mechanism leading to the formation of the new variant, the exon/intron structure of the rat μ-opioid receptor gene in the respective area has been determined by analyzing a genomic P1 phage clone. In addition, we have investigated the putative promoter region of this gene. The present study revealed that rMOR1B is generated by an alternative splicing event whereby a previously unknown exon will be placed behind exon 3 to form rMOR1B mRNA, which is separated from the latter by an intron. Therefore, this new exon has to be called exon 4, whereas the former exon 4, which encodes the C-terminus of MOR1A, now becomes exon 5. Examination of the putative rat promoter region revealed a high degree of nucleotide sequence homology to the mouse gene. Using an RNase protection approach, one single transcription initiation site could be located at 230 bp upstream of the translation start. This is similar to the situation in the mouse, where four major transcription start sites were reported to lie close together around 270 bp upstream of the protein coding region.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Der Schmerz 11 (1997), S. 345-352 
    ISSN: 1432-2129
    Keywords: Schlüsselwörter Capsaicin ; ASS ; Lokaltherapie ; Chronische Schmerzen ; Key words Capsaicin ; ASA ; topical administration ; chronic pain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Objective. To provide a brief review of the current state of topical treatment with capsaicin or acetylsalicylic acid (ASA) for therapy of chronic pain syndromes. Data Sources. A MEDLINE® search was used to find the pertinent literature on "capsaicin" or "ASA" and "chronic pain"; further publications found in these articles were added. Conclusions. Capsaicin is a white crystalline parent compound of a group of vanillyl fatty acid amines. Because of its highly specific action in neurons it has become an important tool in neuroscience. Because of its effects, it is obvious to try for the therapy of circumscribed neuropathic pain. Capsaicin acts by depleting stores of substance P and other neurotransmitters, resulting in a blockade of a specific group of sensory afferents. The corresponding clinical findings are initial burning and a desensitization of specific C fiber nociceptors after repeated application. The pain relieving potency was observed in various clinical investigations and even in a few controlled, double-blind studies about neuropathic pain syndromes and (osteo)arthritis. In contrast to these findings, a recent study found no significant benefit of capsaicin, probably because this study was the first to use an active placebo. Therefore, and because clinical efficacy and advantages over other therapies have not been demonstrated up to now, capsaicin cannot be classified as standard therapy. It may be a therapeutic option as an alternative or as an adjuvant treatment. Pain reduction was also observed after topical application of ASA/ether mixture in the one and only controlled double-blind study on this issue. Therefore, topical ASA therapy for (post)herpetic neuralgia is mainly based on a few enthusiastic case reports rather than on well founded investigations. Furthermore, the discrimination of local from systemic effects, the toxicological profile of longterm topical treatment, and the mechanism of action has not been evaluated. In conclusion, topical ASA cannot be recommended for routine clinical use at present.
    Notes: Zusammenfassung Ziel der vorliegenden Arbeit ware es, bisherige Untersuchungen zur Lokaltherapie chronischer Schmerzen mit Casaicin und Acetylsalicylsäure (ASS) zusammenzustellen und daraus entsprechend den Ausführungen von Tryba und Zenz eine Empfehlung im Sinne einer "evidence-based-medicine" abzuleiten. Eine Lokaltherapie mit ASS oder Capsaicin wurde meist bei neuropathischen Schmerzen, z.B. der postzosterische Neuralgie (PZN) versucht, die Capsaicin-Therapie auch bei Gelenkschmerzen. Die spezifischen Wirkungen von lokal appliziertem Capsaicin, z.B. die Freisetzung von Neurotransmittern, begründen die Erwartung klinisch relevanter Effekte bei chronischen Schmerzen. Demgegenüber erscheint die Rationale einer Lokaltherapie mit ASS weniger naheliegend. An Patienten wurde Capsaicin häufiger als ASS untersucht. Zielgröße der Untersuchungen war hauptsächlich die analgetische Wirksamkeit per se. Für Capsaicin gibt es Befunde über eine Analgesie aus plazebokontrollierten Studien. Allerdings ist in diesen wegen der (Neben-)Wirkung von Capsaicin – Hautbrennen nach initialer Anwendung – die Verblindung problematisch. Die bisher einzige Untersuchung mit aktivem Plazebo zeigte keine Wirksamkeit der Lokaltherapie. Neben positven Daten aus Fallberichten gibt eine plazebokontrollierte Untersuchung über die lokale Anwendung von ASS Anhalt für eine Analgesie bei der postherpetischen Neuralgie. Harte Daten zur Wirksamkeit und Unbedenklichkeit einer Langzeit-Therapie fehlen. Für beide Substanzen bleibt offen, welche klinische Relevanz etwaige positive Therapieeffekt haben und wie ihr Stellenwert gegenüber anderen Therapieverfahren ist. Insgesamt ist eine topische Behandlung mit Capsaicin bzw. ASS bisher nicht als fundierte Therapie zu bewerten.
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  • 3
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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