Tephrosia sinapou ethyl acetate extract inhibits inflammatory pain in mice: Opioid receptor dependent inhibition of TNFα and IL-1β production

Abstract

Context. Tephrosia toxicaria is currently known as Tephrosia sinapou (Buc'hoz) A. Chev. (Fabaceae) and is a source of compounds such as flavonoids that inhibit inflammatory pain.

Objective: To investigate the analgesic effect and mechanisms of the ethyl acetate extract of T. sinapou in inflammatory pain in mice.

Materials and methods: Behavioral responses were evaluated using mechanical (1–24 h) and thermal hyperalgesia (0.5–5 h), writhing response (20 min) and rota-rod (1–5 h) tests. Neutrophil recruitment (myeloperoxidase activity), cytokines (tumor necrosis factor [TNF]α and interleukin [IL]-1β), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels were determined by colorimetric assays. Pharmacological treatments were opioid receptor antagonist (naloxone, 0.1–1 mg/kg) and control opioid (morphine, 5 mg/kg). Inflammatory stimuli were carrageenin (100 µg/paw), complete Freund’s adjuvant (CFA, 10 µl/paw), prostaglandin E₂ (PGE₂, 100 ng/paw) and acetic acid (0.8%).

Results: The intraperitoneal pre-treatment with extract inhibited in a dose-dependent (30–300 mg/kg) dependent manner the mechanical hyperalgesia induced by carrageenin (up to 93% inhibition). The post-treatment (100 mg/kg) inhibited CFA-induced hyperalgesia (up to 63% inhibition). Naloxone (1 mg/kg) prevented the inhibitory effect of the extract over carrageenin-induced mechanical (100%) and thermal (100%) hyperalgesia, neutrophil recruitment (52%) and TNFα (63%) and IL-1β (98%) production, thermal threshold in naïve mice (99%), PGE₂-induced mechanical hyperalgesia (88%) and acetic acid-induced writhing response (49%). There was no significant alteration in the rota-rod test, and AST and ALT serum levels by extract treatment.

Discussion and conclusion. Tephrosia sinapou ethyl acetate extract reduces inflammatory pain by activating an opioid receptor-dependent mechanism.

• Abdominal contortions
• cytokine
• hot plate
• hyperalgesia
• morphine
• myeloperoxidase
• neutrophil recruitment
• nociception
• writhing test

Acknowledgements

We appreciated the technical support of Jesus A. Vargas and Pedro S. R. Dionísio Filho.