α-Terpineol, a monoterpene alcohol, complexed with β-cyclodextrin exerts antihyperalgesic effect in animal model for fibromyalgia aided with docking study

The anti-hyperalgesic effect of the complex containing alpha-terpineol (alpha TPN) and beta-cyclodextrin (beta CD) was analyzed in a non-inflammatory chronic muscle pain model, as well as its mechanism of action through docking study for a possible interaction with receptors. The alpha TPN-beta CD complex was prepared and characterized through the thermogravimetry/derivate thermogravimetry (TG/DTG), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The model of chronic muscle pain was induced by two injections of pH 4.0 saline (20 mu l) into the left gastrocnemius 5 days apart. After confirming hyperalgesia, male mice were treated with alpha TPN-beta CD (25, 50 or 100 mg/kg; p.o.) or vehicle (saline 0.9%, p.o.) daily for 10 days. 1 h after the mechanical hyperalgesia, motor performance was evaluated. In addition, the systemic administration of naloxone and ondansetron tested the analgesic effect on the active opioid and serotonin receptors, respectively. The characterization tests indicated that aTPN was efficiently incorporated into bCD. The oral treatment with alpha TPN-beta CD, at all doses tested, produced a significant (p < 0.001) decrease in the mechanical hyperalgesia, without causing any alteration in the force and in motor performance. This analgesic effect was reversed by the systemic administration of naloxone or ondansetron. These findings are corroborated by the docking study described in the present study, which verified a possible interaction of alpha TPN-beta CD with opioid (MU, Kappa, Delta) and 5-HT receptors. Thus, it can be concluded that alpha TPN-beta CD reduced the hyperalgesia followed by the chronic muscle pain model, probably evoked by the descending inhibitory pain system, specifically by opioid and serotoninergic receptors. (C) 2016 Elsevier Ireland Ltd. All rights reserved.