Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

<p>Abstract</p> <p>Background</p> <p>Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics.</p> <p>Discussion</p> <p>In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.</p> <p>As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy.</p> <p>Summary</p> <p>Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves) to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies.</p

Eine seltene Komplikation nach Le Fort I Osteotomie

Einleitung: Tubenfunktionsstörungen nach Le-Fort-I-Osteotomie sind in der Literatur selten beschrieben. Eine 22 Jahre junge Frau unterzog sich wegen einer maxillären Retrognathie einer Le-Fort-I-Osteotomie. Kurze Zeit postoperativ kam es zu rezidivierenden Tubenfunktionsstörungen mit Paukenergüssen linksseitig. Keine Besserung trotz Adenotomie, Tonsillektomie und Paukenröhrcheneinlagen. Methode: Zur Klärung eines Zusammenhangs der Ohrsymptomatik mit der Le-Fort-I-Osteotomie wurden hochauflösende CT- und MRT-Untersuchungen durchgeführt. Ergebnis/Schlussfolgerung: Es zeigte sich sowohl eine Vorverlagerung des linken Hamulus pterygoideus als auch eine Schädigung des M. tensor veli palatini; beides kann für die postoperativ aufgetretenen Tubenfunktionsstörungen verantwortlich sein

Nasalance distance and ratio: Two new measures

Objectives: Mean nasalance in speakers with perceptually normal nasal resonance can differ in magnitude considerably. In addition, categorizations of speech based on nasalance scores may not agree with perceptual judgments. To overcome this limitation, we evaluated two new simple measures derived from mean nasalance data: the nasalance distance (range between maximum and minimum nasalance) and the nasalance ratio (minimum nasalance divided by maximum nasalance). Setting: Department of Oral and Maxillofacial Surgery, University of Technology, Munich, Germany. Subjects: The sample consisted of 133 cleft lip and palate patients with normal nasal resonance or varying degrees of hypernasality. Procedures: Oral and nasal acoustic measurements were made using the NasalView system. Nasalance distance and nasalance ratio were calculated for five nonnasal and three nasal sentences from the modified Heidelberg Rhinophonia Assessment Form. Results: Optimum cutoffs were derived from Receiver-Operating Characteristics. Results for the sentence stimuli ranged from 64.4% to 89.6% sensitivity and from 91.2% to 94.1% specificity. When the analysis was limited to only one nonnasal and one nasal sentence, results ranged from 79.7% to 87.5% sensitivity and from 88.2% to 97.1% specificity. Conclusions: We conclude that the two new measurements are valuable in routine clinical examinations. Nasalance distance and ratio derived from sentence stimuli are two useful and easily applicable measures that can be used to supplement the nasalance mean value.link_to_subscribed_fulltex