Pharmacological and toxicological evaluations of the new pyrazole compound (LQFM-021) as potential analgesic and anti-inflammatory agents.

Chronic inflammation is a world health problem. There is a need to develop new anti-inflammatory and analgesic drugs with improved activity and reduced side effects. In this context, the aim of this study was to evaluate the antinociceptive and anti-inflammatory effects of the pyrazole compound LQFM-021 after acute and sub-chronic administration in rats submitted to a CFA-induced chronic arthritis model, as well as compare the toxicity of this compound to that of dipyrone, given throughout 7 days. Firstly, we observed that acute oral administration of the higher dose (130 µmol/kg) of LQFM-021 reduced paw lifting time (PET) and edema formation. These effects disappeared on the following day, requiring another dose to maintain the effects. This dose also promoted reduction of the polymorphonuclear recruitment in the synovial fluid. In another experiment, both treatments with LQFM-021, 65 µmol/kg twice a day and 130 µmol/kg once a day, produced a progressive and permanent reduction of the PET and edema, also reducing polymorphonuclear recruitment. However, the single treatment with 130 µmol/kg was more effective than the double treatment with 65 µmol/kg. LQFM-021 did not produce toxicity signs. However, dipyrone (130 µmol/kg once a day) promoted erosion of the epithelial cells and decreased mucus in the gastric mucosa. These data indicate that LQFM-021 produced antinociceptive and anti-inflammatory effects in CFA-induced arthritis in rats. These effects occurred in the absence of apparent toxic effects, indicating that the pyrazole compound LQFM-021 may be considered a good prototype for development of new analgesic/anti-inflammatory drug.

Neural mobilization and static stretching in an experimental sciatica model: an experimental study / Mobilização neural e alongamento estático em um modelo experimental de ciatalgia: estudo experimental

OBJECTIVE: To verify the effectiveness of neural mobilization and static stretching in reducing pain in rats submitted to experimental sciatica. METHODS: The rats (n=23) were divided into three groups: sham (SG/n=8), without intervention; stretching (STCG/n=8), treated with static stretching; and neural mobilization (NMG/n=7), treated with neural mobilization. The animals underwent an experimental model of sciatica by compression of the right ischiatic nerve with catgut suture thread. There were five consecutive sessions of treatment that began on the third day after lesion. The pain caused by the sciatica was evaluated by a functional incapacitation test that measured paw elevation time (PET), and values over 10s were indicative of pain. PET was measured at the following moments: before the lesion (M1), immediately before (M2) and after the first session (M3), immediately after the last session (M4) and 24h after the last session (M5). ANOVA was applied with repeated measures and unrepeated measures for intra- and inter-group comparison, respectively. RESULTS: In the SG, post-lesion PETs were greater than M1 (p<0.001), suggesting persistence of pain. In the STCG, post-lesion PETs were greater than M1 (p<0.001), but lower when comparing M3 vs. M4 (p<0.05) and M3 vs. M5 (p<0.01) suggesting the effectiveness of the treatment. In NMG, M2, M3 (p<0.001) and M4 (p<0.05) were greater in relation to M1, but not M5, showing that this treatment reestablished the normal PET values. CONCLUSION: Both forms of therapy were effective in reducing pain, with neural mobilization being the more effective of the two.

OBJETIVO: Verificar a eficácia da mobilização neural e do alongamento estático na redução da dor em ratos submetidos à ciática experimental. MÉTODOS: Os ratos (n=23) foram divididos em três grupos: simulacro (GS/n=8), sem intervenção; alongamento (GAL/n=8), tratados com alongamento estático; e mobilização neural (GMN/n=7), tratados com mobilização neural. Submeteram-se os animais a um modelo experimental de ciática, comprimindo o nervo isquiático direito com fio de catgut. Realizaram-se cinco sessões consecutivas de tratamento que se iniciaram no terceiro dia pós-lesão. Avaliou-se a dor, provocada pela ciática, pelo teste de incapacidade funcional que mensurava o tempo de elevação da pata (TEP) do animal, e valores maiores que 10 segundos eram indicativos de dor. O TEP foi mensurado nos momentos: antes da lesão (M1), imediatamente antes (M2), após a 1ª sessão (M3), imediatamente após a última sessão (M4) e 24 horas após a última sessão (M5). Aplicou-se ANOVA com medidas repetidas e não repetidas para análise intra e intergrupos, respectivamente. RESULTADOS: No GS, os TEPs no pós-lesão foram maiores que M1(p<0,001), sugerindo persistência da dor. No GAL, os TEPs foram maiores no pós-lesão em relação a M1 (p<0,001), mas diminuiu nas comparações M3xM4 (p<0,05) e M3xM5 (p<0,01) sugerindo a eficácia do tratamento. No GMN, M2, M3 (p<0,001) e M4 (p<0,05) foram maiores em relação a M1, mas M5 não, mostrando que este tratamento restabeleceu os valores normais de TEP. CONCLUSÃO: As duas formas de terapia foram eficazes na redução da dor, sendo a mobilização neural mais efetiva.