Anxiety has been described as an important comorbidity in patients suffering from chronic pain. However, in animals the connection between persistent pain and anxiety has hardly been investigated. Therefore, in the current study it was assessed whether chronic pain also causes anxiety-like behaviour in animals and if it can be reversed by analgesic or anxiolytic drugs. Neuropathic pain was induced in rats by partial sciatic nerve ligation (PNL) and chronic constriction injury (CCI). Mechanical hypersensitivity was assessed by the "electronic algometer", while anxiety-like behaviour was measured by using the elevated plus maze. In both neuropathic pain models, rats exhibited mechanical hypersensitivity, whereas a significant increase in anxiety-like behaviour was observed only in CCI rats (time spent in open arms decreased significantly from 99+/-15.8s in sham animals to 33.4+/-7.5s in CCI animals). Furthermore, midazolam (0.5mg/kg; i.p.) significantly reduced anxiety-like behaviour in both sham- and CCI-operated animals without influencing mechanical hypersensitivity. Morphine (3mg/kg; i.p.) and gabapentin (30 mg/kg; i.p.) significantly attenuated anxiety-like behaviour in the CCI lesioned rats: morphine increased entries into open arms from 3.0+/-0.4 to 7.7+/-1.4 (P=0.01), gabapentin elevated this value from 4.7+/-1 to 7.5+/-0.9 (P=0.02). These data suggest that rats subjected to neuropathic pain models develop anxiety-like behaviour which can be reversed by appropriate analgesic treatment. Morphine and gabapentin had no anxiolytic-like effect in sham treated animals, thus their effect on anxiety-like behaviour in the neuropathic pain model is likely indirect via their anti-nociceptive properties.
BackgroundInfections with respiratory viruses can activate the innate immune response - an important host defence mechanism in the early stage of viral infection. Interferon (IFN) release, triggered by virus infection, is an important factor in establishing an antiviral state, where IFN activation occurs prior to the onset of the adaptive immune response.The two ultra-low-dose combination medications, Engystol® and Gripp-Heel®, have documented efficacy for the treatment of the respiratory infections. However, the underlying antiviral mechanisms remain elusive.MethodsIt was the goal to investigate whether Engystol® and Gripp-Heel® display antiviral activity in a prophylactic treatment protocol (2, 24 and 48 h pre-incubation) using a plaque reduction assay and whether the medications affect the release of type 1 IFN in virus-susceptible cell lines and human peripheral blood mononuclear cells (PBMCs).ResultsBoth medications demonstrate prophylactic effect against viral respiratory virus replication. However, when the incubation was continued for up to 5 days, both medications exhibited a pronounced antiviral effect which was dependent on the pre-incubation time. Moreover, in co-stimulated HeLa cells as well as in activated PBMCs Gripp-Heel® and Engystol® demonstrated an increased type 1 IFN production.ConclusionsEngystol® and Gripp-Heel® inhibited the replication of a variety of respiratory viruses. Additionally, we showed that pre-incubation affects the magnitude of the inhibitory effect differently for the various tested viruses. Both medications stimulate type 1 IFN release in different cell systems which suggests that their antiviral activity may be mediated possibly via modulation of the antiviral type 1 IFN host response.
BackgroundVarious medications of natural origin have effectively treated stress-related disorders, such as sleep disturbances and agitated conditions. The efficacy of Neurexan, a multicomponent, low-dose medication, has been demonstrated in observational studies, but its exact mechanism of action has not been determined.MethodsTo characterize the effects of Neurexan on the central nervous system, we analyzed the spectral frequencies of field potentials in four rat brain areas after a single oral administration of Neurexan. Different doses of Neurexan were tested within a crossover design, and effects were compared with vehicle control.ResultsSignificant effects were observed with 0.5 tablets of Neurexan, predominantly on δ- and θ-waves in the frontal cortex and reticular formation (P < 0.01). In the reticular formation, significant changes of δ- and θ-waves occurred as early as during the first hour after administration. The time course revealed a significant and longer-lasting increase of δ- and θ-waves in the frontal cortex and reticular formation, whereas other spectral frequencies were only transiently affected in the frontal cortex, reticular formation, and striatum.ConclusionIn conclusion, this study demonstrated that the low-dose medication Neurexan influences central nervous system activity in rats. The resulting electroencephalographic profile of Neurexan shows several similarities with those of other calming agents, such as Valeriana and Passiflora, suggesting a potential benefit of Neurexan for patients with stress-related disorders. Moreover, this report demonstrates that electroencephalographic signatures are also valid biomarkers for the assessment of low-dose medications, such as Neurexan.
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