Evaluation of antinociceptive effect of pregabalin in mice and its combination with tramadol using tail flick test

The development of combination therapy is a coherent approach in severe pain treatment. The present study investigated the antinociceptive effect of pregabalin alone and in combination with tramadol in acute pain modeling. Therefore, three groups of male mice received either pregabalin [1 to 400 mg/Kg], tramadol [10 to 80 mg/Kg] or their combination intraperitoneally. Then latency time, maximum possible effect [%MPE] and area under curve [AUC] were calculated in tail flick test. The antinociceptive indexes were significantly increased in10, 100 and 200 mg/kg of pregabalin while tramadol showed dose-dependent antinociception [effective dose 50% was 54 to 79 mg/Kg]. The antinociceptive effect of 100 mg/Kg of pregabalin [%MPE = 35 +/- 4%] was similar to that of 50 mg/Kg of tramadol. The combination of non-analgesic doses [10 mg/Kg] of tramadol and pregabalin did not increase%MPE and AUC, but the co-administration of 30 mg/Kg of tramadol with pregabalin [10 mg/Kg] increased all antinociceptive indexes significantly compared to the controls and with each drug alone. In conclusion, pregabalin showed a comparable antinociceptive effect to tramadol. The increase in analgesic effect was observed after the combination of low analgesic doses of tramadol with pregabalin, while the combination of non-analgesic doses of each drug reversed the interaction to antagonism. Therefore to increase the analgesic effect in pain management, more attention should be paid to respecting right proportion of drug combination. Further studies that specify the mechanism[s] and statement of interaction are needed to expand these findings to clinical applications

Comparative histological and immunohistochemical changes of dry type cutaneous leishmaniasis after administration of meglumine antimoniate, imiquimod or combination therapy

This study compared histological and immunohistochemical changes of cutaneous leishmaniasis treated with meglumine antimoniate, imiquimod, and the combination of both therapies. Single blind clinicopathological studies of fifteen patients with old world cutaneous leishmaniasis in Kerman, Iran were included. A total of four patients received a combination of imiquimod [5% cream] and intra-lesional meglumine antimoniate weekly for four weeks. Monotherapy with imiquimod was given to seven patients and four patients were treated with meglumine antimoniate intralesionally. Histological confirmation was performed before and during therapy. Semi-quantitative histological parameters such as numbers of mixed inflammatory cells [cells/mm[2]] and percentages of Langerhans cells [CD1a+], T-cells [CD3+], B-cells [CD20+], and macrophages [CD68+] were calculated immunohistochemically in the dermis and adjacent epidermis. Topical imiquimod significantly reduced mean histiocytic cellular aggregation size [P<0.05]. Meglumine antimoniate reduced parasite load and infected activated histiocytes in the dermis [P<0.05]. Meglumine antimoniate therapy decreased epidermal CD3+ lymphocytes but increased them in the dermis, within the granulomas [P<0.05]. During topical application of imiquimod a depletion of CD1a+ dendritic cells in the epidermis [P<0.05] and slight predominance of dendritic cells in the dermis were observed. Combined therapy and imiquimod monotherapy decreased CD68+ macrophages in the dermis [P<0.05]. Meglumine antimoniate decreases parasite load with considerable effect on up-regulation of T-cells, which demonstrates that meglumine antimoniate works as parasitocidal and immunomodulator, which could be as the first line of treatment. Imiquimod, accentuates the host immune response and reduces granuloma size which could be effective immunomodulator for combination therapy. Monotherapy of imiquimod is less effective than the two other regimens in decreasing parasite load, inflammation and congestion at the inoculated site