RESUMO
Although the mouse model of incisional pain is broadly used, the mechanisms underlying plantar incision-induced nociception are not fully understood. This work investigates the role of Nav1.8 and Nav1.9 sodium channels in nociceptive sensitization following plantar incision in mice and the signaling pathway modulating these channels. A surgical incision was made in the plantar hind paw of male Swiss mice. Nociceptive thresholds were assessed by von Frey filaments. Gene expression of Nav1.8, Nav1.9, TNF-α, and COX-2 was evaluated by Real-Time PCR in dorsal root ganglia (DRG). Knockdown mice for Nav1.8 and Nav1.9 were produced by antisense oligodeoxynucleotides intrathecal treatments. Local levels of TNF-α and PGE2 were immunoenzymatically determined. Incised mice exhibited hypernociception and upregulated expression of Nav1.8 and Nav1.9 in DRG. Antisense oligodeoxynucleotides reduced hypernociception and downregulated Nav1.8 and Nav1.9. TNF-α and COX-2/PGE2 were upregulated in DRG and plantar skin. Inhibition of TNF-α and COX-2 reduced hypernociception, but only TNF-α inhibition downregulated Nav1.8 and Nav1.9. Antagonizing NF-κB and p38 mitogen-activated protein kinase (MAPK), but not ERK or JNK, reduced both hypernociception and hyperexpression of Nav1.8 and Nav1.9. This study proposes the contribution of the TNF-α/p38/NF-κB/Nav1.8 and Nav1.9 pathways to the pathophysiology of the mouse model of incisional pain.
Assuntos
Proteína Quinase 14 Ativada por Mitógeno , NF-kappa B , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Gânglios Espinais/metabolismo , Masculino , Camundongos , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , NF-kappa B/metabolismo , Oligodesoxirribonucleotídeos , Dor Pós-Operatória/tratamento farmacológico , Prostaglandinas E , Canais de Sódio/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
AIM OF STUDY: Adiantum, one of the most widely distributed genera of the family Pteridaceae, is employed in folk medicine worldwide. Adiantum latifolium Lam. has been used in Latin American traditional medicine as anxiolytic, analgesic and antiinflammatory. The present study investigates the antinociceptive and antiinflammatory properties of the methanolic extract of Adiantum latifolium (MEA) in animal models of pain and inflammation to confirm its medicinal use. MATERIAL AND METHODS: The antinociceptive and antiinflammatory activities of MEA were evaluated using the writhing, formalin, and tail-flick tests, carrageenan-induced paw edema and arachidonic acid-induced ear edema. Mice motor performance was evaluated in the rota rod test and the acute toxicity evaluated over 14 days. RESULTS: Intraperitoneal (1-100mg/kg) or oral (100-400mg/kg) administration of MEA produced a dose-related inhibition of acetic acid-induced writhing in mouse. Furthermore, treatment with MEA (100mg/kg) inhibited both the early and late phases of formalin-induced hypernociception. In contrast, MEA (100mg/kg/IP) did not prevent the thermal nociception in the tail-flick test. In addition, MEA (100 and 200mg/kg/IP) inhibited important events related to the inflammatory response induced by carrageenan or arachidonic acid, namely local edema and increase in tissue interleukin-1ß levels. MEA (300mg/kg/IP)-treated mice did not show any motor performance alterations. Over the study period of 14 days, there were no deaths or toxic signs recorded in the group of mice given 1000mg/kg of MEA. CONCLUSION: The results demonstrate that Adiantum latifolium has antinociceptive and antiinflammatory activities, acting through the inhibition of IL-1ß production.
