Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states. In naïve animals, microglia and astrocytes expressed DPP4 protein with one and two orders of magnitude higher than neurons, respectively. DPP4 significantly increased in astrocytes during inflammation and in microglia in neuropathy. Intrathecal application of two DPP4 inhibitors tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation, and milder but significant opioid-independent antihyperalgesic action in the neuropathic model. The opioid-mediated antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors, while vildagliptin affected mainly delta-receptor activity, although mu- and kappa-receptors were also involved. None of the inhibitors influenced allodynia. Our results suggest pathology and glia-type specific changes of DPP4 activity in the spinal cord, which contribute to the development and maintenance of hyperalgesia and interact with endogenous opioid systems.
The aim of this study was to examine the effectiveness of lengthening the humerus in children and young adults. Between 1984 and2005, the Orthopaedic Department of Semmelweis University elongated 11 humeri (ten patients) for reasons of congenital hypoplasia (four cases), osteomyelitis (three cases), epiphyseolysis, growth plate closure after irradiation and obstetrical paralysis (one case each). The study cohort consisted of five females and five males, with an average age at the time of surgery of 17.8 years (range: 12-31 years). In every case, the lengthening was performed with a unilateral Wagner fixator. The lengthening protocol was 1 mm distraction daily (callotasis) after a 7-day latency period. The fixator was removed after total bone healing. Plate fixation or bone transplantation was not used. The average rate of lengthening was 6.2 cm (4.5-10.5 cm), and the achieved lengthening was 27% (range: 16-44%). The average healing index was 32 day/cm. One patient who suffered from temporary radial paresis, and temporary flexion contracture of the elbow was regarded as a complication following placement of the fixator. Based on our results, humeral shortening can effectively be treated with the unilateral Wagner fixator. The main difference between the original Wagner method and our approach is that we were able to leave the fixator in the humerus until total bony reconstruction so there was no need for plate fixation or bone transplantation.
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