Objectives: The aim of this experimental study was to investigate the effects of mad honey (grayanotoxin, GTX), used in complementary medicine for a variety of purposes besides being food, on pain thresholds in normal mice as model for acute pain and diabetic mouse as model for neuropathic pain. Methods: Hind paw withdrawal pain threshold to thermal stimulus was measured with a plantar analgesia meter in a mice model using healthy intact animals for acute pain and streptozotocin-induced diabetic animals for chronic neuropathic pain. Time and dose-dependent effects of intraperitoneally (i.p.) administered GTX were investigated in both acute and neuropathic pain. Results: In the acute pain model, administration of GTX caused a dose- and time-dependent marked increase in the pain latency values. In diabetic mice, which had markedly increased threshold to pain, GTX (0.1 mg/kg, i.p.) restored the mean pain latencies by decreasing from the pre-GTX treatment values of 3.2 ± 0.6 to 3.0 ± 0.9s at 10 min, 3.2 ± 0.6s at 20 min, 3.4 ± 0.6s at 30 min, 2.6 ± 0.5s at 60 min and 2.4 ± 0.6s ( p < 0.05) at 100 min. Conclusion: The results from this experimental study indicate that GTX exhibits significant analgesic activity and has potential benefits against painful diabetic neuropathy. This is compatible with the widespread use of GTX containing mad honey for alleviating pain. Further studies involving long-term applications are needed for a more decisive conclusion regarding the usefulness of GTX as an analgesic, especially in the treatment of painful neuropathy.

Together these results indicate that apelin-13 can cause increased pain sensitivity after peripheral administration, but this effect does not involve calcium mediated signaling in primary sensory neurons.

BackgroundThe aim of this study was to investigate the possible neurotoxic effects of 3 root canal sealers (RCSs) (AH Plus, GuttaFlow, iRoot SP) on cultured rat trigeminal ganglion (TG) neurons.Material and MethodsPrimary cultures of TG neurons were obtained from 1 to 2-day old rats. Freshly mixed RCSs were incubated in sterile phosphate buffered saline and cells were incubated with supernatants of the RCSs for different time intervals (1-, 3-, 6- and 24-h; 1 or 1/10 diluted) and viability/cytotoxicity was tested by counting the number of live cells. Pair of dishes with cells from the same culture incubated with only culture medium was considered as negative controls. Cell images were captured and acquired at x200 magnification using a microscope equipped with a camera using special image program. The viable cells were manually counted assigned from the images for each dose and incubation duration. Data was analysed by using 1-way analysis of variance with Tukey post hoc tests.ResultsThere was no significant change in cell viability after short duration of incubation (1- and 3-h) with the supernatant of any of RCSs, except for undiluted-AH Plus at 3-h. When AH Plus was compared with other RCSs, for diluted supernatants, there was only significant difference between iRoot SP and AH Plus at 24-h (P<0.05). Whereas undiluted-AH Plus was significantly more cytotoxic for 3-, 6- and 24-h periods as compared to respective incubation periods of undiluted other groups (P<0.05). GuttaFlow groups had similar neurotoxic effect on cells for all test periods.ConclusionsAll tested RCSs exhibited a variable degree of neurotoxicity on these primary sensory neurons of orofacial tissues, depending on their chemical compositions. GuttaFlow and iRoot SP evoked a less toxic response to TG cells than AH Plus. Key words:Neurotoxicity, trigeminal ganglia, cell culture, root canal sealer, AH Plus, GuttaFlow, iRoot SP.

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The results of this in vitro study demonstrated that ivabradine inhibits cholinergic agonistinduced bladder contractions, which means that in the future ivabradine may be used in OAB treatment.