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Zusammenfassung Chronische Schmerzen bedingen angesichts ihrer bio-psycho-sozialen Komplexitat und der facherubergreifenden Prasenz eine interdisziplinare Zusammenarbeit. Diese erst ermoglicht eine umfassende Einordnung des Befundes und ist Vorraussetzung fur ein individuelles und ressourcenorientiertes Therapiekonzept mit dem Schwerpunkt der korperlichen und psychischen Aktivierung. Dieses Konzept ist Behandlungsschwerpunkt des UniversitatsSchmerzCentrums (USC), das im April 2004 im Universitatsklinikum Dresden gegrundet wurde und seitdem neben der bereits etablierten ambulanten Therapie auch teilstationare und stationare Versorgung ermoglicht. Ausgangspunkt der Grundungsinitiative fur das Schmerzzentrum war die Sensibilisierung der Kostentrager fur die komplexe Proble-matik des chronischen Schmerzes und ebenso fur die bestehenden regionalen Strukturdefizite. Gefolgt von der Vorlage eines schlussigen multimodalen, fachubergreifenden Behandlungskonzeptes mit ausfuhrlicher Kostenkalkulation wurde nach 1 1 2 -jahriger Arbeitsphase im Juni 2004 ein Vertrag zur integrierten Versorgung mit der AOK Sachsen und dem VdAK unterzeichnet. Nach nun zweijahriger Behandlungsphase sollen erste Erfahrungen und Ergebnisse, insbesondere der tagesklinischen Therapiesaule des Schmerzzentrums innerhalb des IV-Vertrages, dargestellt werden.

The loss of spleen may lead to fatal bacterial infections. To prevent this, splenic autotransplantation has been performed in humans and experimental animals. However, there is still controversy about the protective function of this procedure. Since innervation plays an important role in splenic function, we investigated whether splenic regenerates are re-innervated, and whether this depends on the donor and host age. Splenic tissue (30 mg) was implanted into the greater omentum of either young (2 days) or old (12 months) rats, from either young or old syngeneic animals. After 3 months of regeneration, the weight of the regenerates was determined, PGP + nerve fibers were revealed by immunohistology, and subdivided into nerve fibers of sympathetic (TH + , NPY + ) or sensory (SP + , CGRP + ) origin. In addition, proliferating (Ki-67 proliferation antigen + ) and apoptotic cells (TUNEL technique + ) were likewise investigated. No innervation of splenic regenerates was observed after implantation into old hosts, correlating with poorly developed splenic compartments. In contrast, almost normal re-innervation occurred in young hosts after implantation of both young and old splenic tissue. These regenerates showed well-developed splenic compartments and a normal number and tissue distribution of proliferating and apoptotic cells. However, after the implantation of young tissue, the final size of splenic regenerates was three times larger (140±30 vs. 40±10 mg). Thus, re-innervation of splenic implants is necessary for their subsequent development. It is determined by host age, whereas the final size of the splenic regenerates is regulated by donor age-dependent factors. This model is useful for studying both the process leading to initial innervation and the consequences of this innervation.

Contact hypersensitivity responsiveness to dinitrofluorobenzene is depressed in mice that are sensitized through skin sites exposed to ultraviolet (UV) radiation. Local impairment of contact hypersensitivity by UV has been associated with a reduction in antigen-presenting cell activity within UV-irradiated skin sites marked by a decrease in the density of Ia-positive epidermal Langerhans cells. Our recent studies have demonstrated that neurogenic mediators (e.g. calcitonin gene-related peptide (CGRP) and nitric oxide (NO) contribute to cutaneous inflammation following exposure of rats to high-dose UV radiation. Since CGRP and NO inhibit antigen presentation by dendritic cells in vitro, we have investigated the possible involvement of CGRP and NO in local immunosuppression in UV-irradiated rodents. Hindpaw skin of Sprague-Dawley rats and back skin of UV-susceptible C57BL/6 mice was exposed to acute UV radiation (2.0 J/cm2 and 0.5 J/cm2, respectively). Alterations in cutaneous CGRP content were analyzed by a specific radioimmunoassay (RIA). In separate experiments, the CGRP receptor antagonist CGRP-(8-37) (10-5 M) and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (2 X 10-5 M) were topically applied to UV-exposed skin before induction of contact hypersensitivity with dinitrofluorobenzene. Finally, we examined the effects of UV irradiation and epicutaneous application of CGRP on Ia-positive Langerhans cells by immunohistochemical analysis of epidermal sheets. It was found that UV exposure lead to a decrease in skin CGRP levels starting already 2 h after irradiation and reaching a minimum (less than 40% of non-irradiated control skin) at 6-12 h. Contact hypersensitivity reactions were significantly suppressed by UV radiation in rat skin (by 51%) and murine skin (by 80%). Topical administration of both CGRP-(8-37) and L-NAME before sensitization restored the capacity to respond to haptens applied to UV-exposed skin. Both UV exposure and topical CGRP reduced the density of Ia-positive epidermal cells. Our data indicate that CGRP may be released from sensory neurons following cutaneous UV irradiation and that CGRP and NO contribute of UV-induced local immunosuppression. Moreover, topical administration of CGRP or its antagonist may be able to modulate epidermal Langerhans cell activity in vivo.

DNA analysis using STR amplification become increasingly sensitive permitting the use of minutes quantities of DNA transferred through skin contact. However, in such case, the interpretation of mixed profiles is very difficult due to low intensity peak, allelic drop-out or stutter increase. We use a multiple PCR strategy with post-PCR purification to help interpret low-copy-number DNA profile. To ensure that this approach can be used with minimal risk, we tested post-PCR purification of limited amount of mixed known samples. Results were analysed for correct alleles, allelic drop-out, allelic drop-in and stutter increase. No allelic drop-in was observed and most of the lowest peaks were confirmed by post-PCR purification. However, careful interpretation of peaks present at a stutter position is necessary.