[Diagnostics and therapy of neuropathic pain]. / Diagnostik und Therapie neuropathischer Schmerzen.

Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system. Scientific studies have shown that neuropathic pain is the result of complex altered signalling processes in the peripheral and central nervous system. Current forms of treatment of neuropathic pain are causally oriented but also aim at symptomatic analgesia by pharmacological and nonpharmacological methods. Furthermore, psychological pain management techniques are used in a supportive role. This review summarizes the contemporary diagnostics of neuropathic pain using frequent diseases as examples and presents the evidence from randomized controlled trials on the treatment of neuropathic pain. Treatment guidelines for pharmacological management of neuropathic pain include evidence-based use of antidepressants, anticonvulsants, opioids, capsaicin and lidocaine.

Mutation in Nav 1.7 causes high olfactory sensitivity.

Mutations in the sodium-channel Nav 1.7, encoded by the gene SCN9A, are known to cause pain disorders. In particular, gain-of-function missense mutations in Nav 1.7 have been shown to be causal in primary erythromelalgia. We present a patient with erythromelalgia, pain attacks and hyperosmia with a mutation within the sodium-channel gene SCN9A. A 50-year-old woman presented with burning pain in both feet and abdominal pain attacks developed over the course of 10 years. Furthermore, this patient experienced a hypersensitivity for odours. Clinical investigation as well as serum/cerebrospinal fluid laboratory findings and electrophysiological testing were unremarkable. Olfactory testing showed high olfactory acuity for all screened modalities and good intranasal sensitivity. Furthermore, quantitative sensory testing within the trigeminal area revealed very low thresholds for thermal, tactile and pain detection. In addition, quantitative sensory testing at the lower legs showed hyperalgesia and, as the disease progresses, thermal sensory function loss. Skin biopsies of the proximal and distal lower limbs revealed reduced epidermal nerve fibre density indicating small fibre neuropathy. Genetic analysis of the SCN9A gene demonstrated a heterozygous mutation in Exon 20 - c.3734A>G (p.N1245S). Treatment with clinically available sodium-channel inhibitors did not result in significant pain relief. Local application of the sodium-channel blocker ambroxol however, reduced pain intensity. Continuous odour exposure stabilised mood and induced a short-term pain relief. This clinical note illustrates the course of middle-age onset erythromelalgia and points to clinical findings related to a likely pathogenic missense mutation affecting the sodium-channel Nav 1.7. SIGNIFICANCE: This case report illustrates the course of middle-age onset erythromelalgia with presumed gain-of-function in olfactory and pain sensation associated with a Nav1.7 channel mutation.

[DreKiP - an outpatient treatment program for children and adolescents with headache]. / DreKiP ­ ein ambulantes Therapieprogramm für Kinder und Jugendliche mit Kopfschmerzen.

Headaches are a frequent health problem among children and adolescents. The ocurrence of headaches and the resulting impairments in the quality of life and activities of daily living are modulated by biopsychosocial interactions, which necessitate a complex treatment program. The Dresden Childrens Headache Program (DreKiP) is a multidisciplinary therapy program consisting of eight modules for children and adolescents: education, stress relief, relaxation techniques, physical fitness, climbing therapy, art therapy and sensory training. In addition, there are six modules containing parallel workshops for parents. This outpatient program lasts 2-3 months and is performed parallel to the daily and school routine. Therapy groups consist of 6-8 patients in each age group. In total patients receive 15 h and the parents 7 h of therapy. Concomitant with the program, headache-associated data, such as headache frequency, medication use and school absence are documented. So far 32 children and adolescents in groups of 11, 14-15, 14-16, 17 and 17-18 years old completed the program. Of the 32 patients 19 presented with migraine and tension type headache, 6/32 with migraine and 7/32 with tension type headache only. The median number of headache days was 15 per month and 4 official school absence days per month. Preliminary results 6 months after the end of the therapy program showed reduced frequency of headaches in three quarters of our patients. The headache frequency was reduced from an initial median of 15 days per month to a median of 8 days per month after the program. The multidisciplinary program DreKiP improves the use of therapeutic means in children and adolescents with primary headaches. Children and adolescents with headache-related impairment in activities of daily life in school and leisure times constitute the target group of this therapy.

Effects of analgesics on olfactory function and the perception of intranasal trigeminal stimuli.

BACKGROUND: There is some evidence suggesting that analgesics have an impact on human chemosensory function, especially opioids and cannabinoids are known to interfere with olfactory function. However, largely unknown is the effect of a long-term use of analgesics on the intranasal trigeminal system so far. Here, we investigated olfactory function and the perception of intranasal trigeminal stimuli in pain patients with long-term use of analgesics compared to age-matched healthy controls. METHODS: For this purpose, a psychophysical approach was chosen to measure these sensory functions in 100 chronic pain patients and 95 controls. Olfactory testing was performed using the 'Sniffin' Sticks' test kit, which involves tests for odour threshold, odour discrimination and odour identification. Further, participants were asked to rate the intensity of trigeminal stimuli by using a visual analogue scale. RESULTS: We observed that the chronic use of pain medication was associated with significantly reduced perception of intranasal trigeminal stimuli and olfactory function compared to age-matched controls without intake of analgesics. Results indicate that non-opioid and opioid drugs, or a combination of both did not differ in their effects on chemosensory function. Further, after eliminating the effect of a co-existing depression and the use of co-analgesics, the negative influence of analgesics on olfactory function and trigeminal perception was still evident. CONCLUSION: The observed effect might be mediated due to interaction with opioid receptors in trigeminal ganglia and nuclei or due to trigeminal/olfactory interaction. As a practical consequence, patients should be made aware of a possible impairment of their olfactory and trigeminal function under long-term analgesic treatment. WHAT DOES THIS STUDY ADD?: We observed that the chronic use of pain medication was associated with significantly reduced olfactory function and perception of intranasal trigeminal stimuli compared to age-matched controls without intake of analgesics. Non-opioid and opioid drugs did not differ in their effects on chemosensory function.

[Postherpetic neuralgia]. / Postzosterneuralgie.

Postherpetic neuralgia is considered to be a neuropathic pain syndrome. Typically, patients experience pain in the dermatomes of skin lesions persisting for more than 3 months after skin restitution. About 10% of patients with herpes zoster develop postherpetic neuralgia. Its prevalence increases with age. Common clinical symptoms include continuous burning pain, sharp pain attacks, and allodynia. Additionally, sensory hyperactivation or loss in the affected skin area is present. Pathophysiology includes mechanisms of peripheral and central sensitization, based on damaged nerve fibers as the main mechanisms for pain generation and its maintenance. Clinical studies did show pain relief in postherpetic neuralgia after administration of antidepressants, antiepileptic drugs, opioids, and topical capsaicin and lidocaine. Nevertheless, about one third of patients do not respond to conventional treatment. Given the fact that postherpetic neuralgia is considered to be a chronic pain disease, a multidisciplinary treatment approach is necessary.

[Postherpetic neuralgia]. / Postzosterneuralgie.

Postherpetic neuralgia is considered to be a neuropathic pain syndrome. Typically, patients experience pain in the dermatomes of skin lesions persisting for more than 3 months after skin restitution. About 10 % of patients with herpes zoster develop postherpetic neuralgia. Its prevalence increases with age. Common clinical symptoms include continuous burning pain, sharp pain attacks, and allodynia. Additionally, sensory hyperactivation or loss in the affected skin area is present. Pathophysiology includes mechanisms of peripheral and central sensitization, based on damaged nerve fibers as the main mechanisms for pain generation and its maintenance. Clinical studies did show pain relief in postherpetic neuralgia after administration of antidepressants, antiepileptic drugs, opioids, and topical capsaicin and lidocaine. Nevertheless, about one third of patients do not respond to conventional treatment. Given the fact that postherpetic neuralgia is considered to be a chronic pain disease, a multidisciplinary treatment approach is necessary.

[Postherpetic neuralgia]. / Postzosterneuralgie.

Postherpetic neuralgia is considered to be a neuropathic pain syndrome. Typically, patients experience pain in the dermatomes of skin lesions persisting for more than 3 months after skin restitution. About 10% of patients with herpes zoster develop postherpetic neuralgia. Its prevalence increases with age. Common clinical symptoms include continuous burning pain, sharp pain attacks, and allodynia. Additionally, sensory hyperactivation or loss in the affected skin area is present. Pathophysiology includes mechanisms of peripheral and central sensitization, based on damaged nerve fibers as the main mechanisms for pain generation and its maintenance. Clinical studies did show pain relief in postherpetic neuralgia after administration of antidepressants, antiepileptic drugs, opioids, and topical capsaicin and lidocaine. Nevertheless, about one third of patients do not respond to conventional treatment. Given the fact that postherpetic neuralgia is considered to be a chronic pain disease, a multidisciplinary treatment approach is necessary.

[Chronic non-cancer-related pain. Long-term treatment with rapid-release and short-acting opioids in the context of misuse and dependency]. / Chronische nichttumorbedingte Schmerzen. Langzeitbehandlung mit schnell freisetzenden und kurz wirksamen Opioiden im Kontext von Missbrauch und Abhängigkeit.

Annually published data show a continual increase in the volume of opioid prescriptions in Germany, thus indicating an intensification of opioid therapy. The majority of opioids are prescribed to treat chronic non-cancer-related pain. On the basis of current guidelines, as well as in terms of the lack of data regarding long-term use of opioids and their effectiveness beyond a period of 3 months, this development must be viewed critically. With reference to four case reports, we discuss and evaluate opioid therapy in relation to medication misuse and the development of drug dependency. Particular emphasis is placed on the administration of rapid-release and short-acting opioid preparations, which we consider to be particularly problematic.

[Physicians' knowledge and attitudes concerning the use of opioids in the treatment of chronic cancer and non-cancer pain]. / Befragung schmerztherapeutisch interessierter Arzte zum Umgang mit Opioiden.

INTRODUCTION: The efficacy of opioids has been proved and several guidelines and expert panel-based recommendations regarding the use of opioids in different pain syndromes are available. Nevertheless, undertreatment of pain with strong opioids was reported in previous studies. It was shown that physicians' lack of knowledge, their concerns and misconceptions about the opioid use and the controlled substances regulations that govern the prescriptions of opioids occasionally contribute to insufficient pain treatment. This study was designed to evaluate German physicians' knowledge and their concerns about the use of opioids. METHOD: During a postgraduate course a questionnaire was completed by German physicians specializing in pain therapy. RESULTS: A total of 226 physicians completed the questionnaire (response rate 57%). Many of them had poor knowledge of the WHO recommendations for the treatment of cancer pain including the WHO analgesic ladder. Deficiencies in the knowledge of pharmacological aspects and controlled substances regulations were revealed. Many physicians would prescribe strong opioids for non-opioid-sensitive types of pain. The concerns regarding opioid therapy included adverse effects and addiction. In contrast to earlier findings the German controlled substances regulations no longer seem to be a barrier to the prescription of opioids in the treatment of chronic severe pain since they were changed in 1998. As a result, the lack of knowledge and the physicians' concerns about the use of opioids as shown in this survey may likely lead to an insufficient treatment of patients suffering from severe chronic pain. CONCLUSION: It is necessary to improve the medical students' education and the physicians' postgraduate training regarding principles of pain management such as the WHO guidelines for the treatment of cancer pain. A better knowledge of important pharmacological aspects of opioids should help to reduce physicians' concerns about the use of strong opioids. Nevertheless, improvement of physicians' skills in pain therapy is only one aim in a multidisciplinary concept in order to improve patients' pain therapy.

[Evaluation of a multimodal pain therapy at the University Pain Centre Dresden]. / Evaluation einer multimodalen Schmerztherapie am UniversitätsSchmerzCentrum Dresden.

BACKGROUND: Data of a multimodal pain management program of the multidisciplinary pain management centre at the University Hospital of Dresden is presented. Over a period of 4 weeks, supplemented by an additional week 3 months later (booster week), patients with chronic pain of different origins are being treated in groups of 12. Based on the principles of the biopsychosocial pain model and the idea of functional restoration, the program is dedicated for pain patients where outpatient treatment was insufficient. METHODS: The program was evaluated on the basis of pain intensity (NRS), pain disability (PDI), fear and depression (HADS-D), catastrophizing (CSQ) and health-related quality of life and vitality (SF-36). The data were collected at the beginning and end of the initial 4 week treatment period, at the end of the booster period as well as 6 and 12 months after the end of active treatment. RESULTS: A total of 189 patients were included in the program in the period from January 2006 until August 2008. All outcome parameter showed statistically significant improvements with small to high effect sizes (ES 0.20-0.95). The results stayed stable even 1 year after the treatment. The highest effect sizes were found in catastrophizing (ES 0.86) and average pain intensity (ES 0.95). The primary pain diagnosis (e. g. low back pain versus headache) had no impact on treatment outcome. CONCLUSION: Significant and clinically relevant improvements could be achieved with the multimodal pain management program in groups of 12 patients. The results were stable over a time period of 1 year. Pain diagnosis had no impact on the outcome.

[Elektrophysiological methods as diagnostic tools in pain therapy]. / Elektrophysiologische Messverfahren in der Schmerztherapie.

Elektrophysiological methods provide objective data about the function of the somatosensory system. Broadly established methods like neurography, myography, sensory evoked potentials and electrically evoked reflexes are in contrast to less well known techniques as laser-evoked potentials and microneurography. It is important to keep in mind that neurography and sensory evoked potentials comprise the function of myelinated nerve fibers with big axonal diameters. Unlike, laser-evoked potentials and microneurography describe the functionality of nonmyelinated, small diameter nerve fibers, which transmit pain and temperatures as sensory signals. Investigation of the sympathetic sudomotoric system can provide evidence for lesions within sympathetic nerves.

[Thunderclap headache caused by cerebellar infarction]. / Thunderclap headache durch Kleinhirninfarkt.

Thunderclap headache is an acute and severe headache and is often the first sign of a life-threatening neurovascular disorder. The case of a 44-year-old man is described who presented with a thunderclap headache as the only clinical symptom. The clinical examination did not reveal any other focal deficits or signs of motor or sensory failures. Routine blood tests, cerebral CT as well as cerebrospinal fluid analysis showed no pathological results. A cerebral MRI to exclude a symptomatic thunderclap headache revealed a right cerebellar infarction. This case expands the differential diagnosis of thunderclap headache and reinforces the need for magnetic resonance imaging in the evaluation of such patients, even when neurological examination, cerebral CT, and cerebrospinal fluid analysis are normal.

Analysis of the polymorphic prion protein gene codon 129 in idiopathic Parkinson's disease.

Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder of unknown aetiology. Histopathological similarities between IPD and Creutzfeldt-Jakob prion disease (CJD) have been suggested. Homozygosity at polymorphic prion protein gene codon 129 (PRNP129) is a risk factor for developing CJD. Therefore we investigated a putative genetic link between CJD and IPD by studying PRNP129 genotype segregation in 81 patients with IPD. We did not ascertain a different PRNP129 genotype distribution in IPD patients compared to healthy Germans. We found a significant difference in PRNP129 genotype in dependence of the clinical predominance type of IPD. Patients with tremor-dominant IPD presented less frequent a methionine homozygosis at PRNP129 than hypokinetic-rigid IPD patients (30% versus 62.5%; p<0.033). In conclusion, genotype distribution at codon 129 is obviously not essential in determining IPD. But our results may provide first evidence of an association between certain PRNP129 polymorphisms and the clinical presentation of IPD.

Distinct factors correlating with adverse cardiac events after major vascular surgery.

INTRODUCTION: Cardiovascular complications remain the principal cause of both morbidity and mortality after major vascular surgery. The well-known coincidence between vascular disease and coronary artery disease provided the rationale for a detailed analysis of major perioperative cardiovascular complications in their relation to preoperative and intraoperative parameter METHODS AND PATIENTS: 90 patients scheduled to undergo either femoral-popliteal bypass (n = 74) or repair of an infrarenal aortic aneurysm (n = 16) were prospectively included in the study. All patients had no signs of unstable cardiac disease and required no cardiac testing. Both preoperative and intraoperative parameter were correlated to adverse cardiac events (cardiac death and myocardial infarction -MI). RESULTS: Univariate analysis identified the following parameter to be significantly related to cardiac complications: prior MI and intraoperative hypertension (systolic blood pressure above 200 mmHg). In contrast perioperative betablocker therapy was revealed to be protective. In multivariate analysis the history of MI and intraoperative hypertension correlated with poor cardiac outcome. CONCLUSIONS: Our results underline the importance of the individual history in predicting perioperative risk and corroborate the beneficial effects of long-standing beta-blocker therapy. Additionally the significance of stable intraoperative hemodynamic parameter is demonstrated.

Apolipoprotein E and alpha-1-antichymotrypsin polymorphisms in sporadic inclusion body myositis.

Sporadic inclusion body myositis (s-IBM) is a progressive muscle disease of unknown aetiology. Characteristically, intracellular amyloid deposits are detectable, including beta-amyloid precursor protein, phosphorylated tau, alpha1-antichymotrypsin (alpha1-ACT) and apolipoprotein E (ApoE). Polymorphisms and mutations of the encoding genes have been identified in a variety of neurodegenerative diseases including Alzheimer's disease (AD). Beside other factors, polymorphisms may lead to protein accumulation in both diseases. In particular, polymorphisms within the ApoE and alpha1-ACT gene have been implicated in the aetiology of AD and s-IBM. We analysed ApoE and alpha1-ACT gene polymorphisms in 35 s-IBM patients. We could not identify any statistical significant correlation between distinct ApoE and alpha1-ACT genotypes and the risk of developing s-IBM. Additionally, ApoE and alpha1-ACT genotypes seem not to influence the onset age of s-IBM. A combination of different alpha1-ACT and ApoE genotypes appears not to enhance the risk of developing s-IBM. Therefore, allelic variations of alpha1-ACT and ApoE are unlikely to be genetic key factors in the aetiology of s-IBM.

HLA typing and Parkinson's disease.

Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder of unknown aetiology. Several antigens have been associated with IPD using serological methods. We systematically analysed HLA class I and II alleles in 45 German Caucasian IPD patients using sequence-specific oligonucleotides and sequence-specific primer technology. Applying Bonferroni adjusted p values, we demonstrate a statistically significant increase of the DQB1*06 allele (p = 0.002) in IPD which may indicate an association between IPD and the immune system. Alternatively, HLA alleles might be in linkage disequilibrium with genes located next to the HLA locus.

[Sterile eosinophilic pustulosis (Ofuji). A rare entity in Europe]. / Sterile eosinophile Pustulose (Ofuji). Eine in Europa seltene Entität.

This case report refers to a German patient with sterile eosinophilic pustulosis of the Ofuji type (SEP), which is rarely described in non-Japanese humans. The distinctive histomorphology, with intraepidermal eosinophilic abscesses and eosinophilic folliculitis, is complemented in this patient by marked eosinophilia, evident eosinophilic bone marrow reaction and involvement of the oral mucosa with eosinophilic spongiosis, which is a feature that had not previously been reported. Possible transitions between cutaneous and internal hypereosinophilic syndromes are discussed. Despite the initial good effect of topical corticosteroids on the cutaneous changes, long-term follow-up to check for internal involvement is necessary.