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Background and aims: Preclinical animal models are crucial to study pain mechanisms and assess antinociceptive effects of medications. One major problem with current animal behavioral models is their lack of face validity with human nociception and the vulnerability for false-positive results. Here, we evaluated the usefulness of rotarod as a new way to assess inflammatory nociception in rodents. Methods: Adult male mice were injected with saline or Complete Freund's Adjuvant (CFA) in the left hindpaws. Mechanical allodynia and rotarod performance were evaluated before and after the administration of CFA. Mechanical allodynia was measured using von Frey filaments. Long-term effect of CFA on rotarod performance was also assessed for 2 weeks. Results: Our results showed that CFA administration decreased pain threshold and increased sensitivity to von Frey filaments compared to control group. In rotarod experiments, the starting speed of the rod rotation started at four RPM, and accelerated until it reached 40 RPM in 5 min. Rotarod performance was enhanced from day to day in the control group. However, rotarod performance in CFA group was attenuated after CFA administration, which was significant after 24 h compared to vehicle. This attenuation was blocked by ibuprofen. Haloperidol administration (positive control) produced similar results to CFA administration. CFA did not produce significant attenuation of rotarod performance after 1 week post-injection. Conclusions: Collectively, our findings could encourage the use of rotarod assay to measure acute (but not chronic) inflammatory nociception as a useful tool in rodents. [ABSTRACT FROM AUTHOR]

Resumo Justificativa e objetivos O fenômeno doloroso é uma das mais importantes e complexas experiências. A fentolamina é antagonista alfa‐adrenérgico não seletivo. O objetivo foi comparar os efeitos de doses crescentes da fentolamina, por via subaracnóidea, em ratos na modulação do fenômeno doloroso. Método Foram usados 84 ratos Wistar machos, divididos nos grupos formalina e incisão plantar, subdivididos em seis subgrupos (n = 7). No subgrupo controle (GC) apenas salina (10 μL), nos subgrupos ativos, 10 μg de fentolamina (GF10), 20 μg (GF20), 30 μg (GF30), 40 μg (GF40) e 50 μg (GF50). No grupo formalina, a dor foi induzida com injeção de 50 μL de formalina a 2%, na região dorsal da pata posterior direita. No grupo incisão plantar, a dor foi induzida por incisão plantar e avaliação pelos filamentos de Von Frey. Indução e manutenção anestésica com halotano a 3% para introdução de cateter no espaço subaracnóideo e feitura da incisão plantar. Análise estatística dos resultados pelo programa JMP do SAS com nível de significância 5%. Resultados A fentolamina nas doses de 20 e 30 μg produziu aumento da resposta álgica na fase intermediária do teste da formalina. No teste da incisão plantar, promoveu efeito hiperálgico no primeiro, terceiro, quinto e sétimo dias na dose de 10 μg, no primeiro, terceiro e quinto dias na dose de 20 μg e no quinto dia na dose de 30 μg. Conclusão A fentolamina por via subaracnóidea promoveu efeito hiperálgico, possivelmente pela participação de diferentes subclasses de receptores alfa‐adrenérgicos nas vias modulatórias da dor. Background and objectives Painful phenomenon is one of the most important and complex experiences. Phentolamine is a non‐selective alpha‐adrenergic antagonist. The objective of this study was to compare the effect of increasing doses of phentolamine into subarachnoid space in rats in the modulation of painful phenomenon. Methods 84 male Wistar rats were divided into formalin and plantar incision groups, subdivided into six subgroups (n = 7). Control group (CG) received only saline (10 μL); active subgroups received phentolamine 10 μmg (GF10), 20 mg (GF20), 30 mg (GF30), 40 mg (GF40), and 50 g (GF50). In formalin group, pain was induced by injection of 50 μL of 2% formalin in dorsal region of right posterior paw. In plantar incision group, pain was induced by plantar incision and evaluated using Von Frey filaments. Induction and maintenance of anesthesia were performed with 3% halothane for catheter placement into subarachnoid space and plantar incision. Statistical analysis was performed using the JMP program from SAS with 5% significance level. Results Phentolamine at doses of 20 and 30 g increased the algesic response in the intermediate phase of the formalin test. In plantar incision test, it had hyperalgic effect on first, third, fifth, and seventh days at a dose of 10 g and on first, third, and fifth days at a dose of 20 g and on fifth day at a dose of 30 g. Conclusion Subarachnoid administration of phentolamine showed hyperalgesic effect, possibly due to the involvement of different subclasses of alpha‐adrenergic receptors in modulating pain pathways. [ABSTRACT FROM AUTHOR]