Effects of an ethanol extract and the diterpene, xylopic acid, of Xylopia aethiopica fruits in murine models of musculoskeletal pain

Abstract

Context: Fruits of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) are used traditionally to manage arth- ritis, headache and other pain disorders. Objective: The analgesic properties of the X. aethiopica ethanol fruit extract (XAE) and xylopic acid (XA) were evaluated in musculoskeletal pain models. Materials and methods: Acute muscle pain was induced in gastrocnemius muscle of Sprague–Dawley rats with 3% carrageenan (i.m.). Rats received XAE (30–300 mg/kg), XA (10–100 mg/kg) or morphine (1–10 mg/ kg) after 12 h. Effects of XAE and XA on muscle pain were assessed by measuring post-treatment grip strength of the rats. Chronic muscle pain was similarly induced, but drug treatment was on the eighth day and effects of XAE and XA assessed with Randall–Selitto test for hyperlagesia. Acute-skeletal pain was induced in knee joints of rats with 3% carrageenan-kaolin mixture and effects determined 12-h later. Similar induction protocol was used for chronic knee pain with treatment and measurement as done for chronic muscle pain. Results: XAE and XA significantly and dose-dependently ameliorated both acute muscle (ED50 mg/kg: XAE ¼ 22.9; XA ¼ 6.2) and skeletal hyperalgesia (XAE ¼ 39.9; XA ¼ 17.7) induced by 3% carrageenan. Similarly, chronic skeletal hyperalgesia was reduced by XAE and XA treatment similar to morphine (ED50: XAE ¼ 13.0; XA ¼ 4.6). This reduction was also seen in chronic muscle hyperalgesia (ED50: XAE ¼ 79.1; XA ¼ 42.7). XAE and XA significantly reduced the spread of hyperalgesia to contralateral limbs in both models of chronic hyperalgesia. Conclusion: These findings establish analgesic properties of the ethanol fruit extract of X. aethiopica and xylopic acid in musculoskeletal pain.