betadex and Musculoskeletal-Pain

Myrtenol has gained wide interest because of its pharmacological profiles, mainly for treatment of chronic diseases. To improve the solubility of myrtenol, the formation of inclusion complexes with β-cyclodextrin was performed by physical mixture, kneading process or slurry complexation (SC) methods and characterized using thermal analysis, XRD, SEM and NMR. From these results, myrtenol complexed by SC was successfully complexed into β-cyclodextrin cavity. The interaction between myrtenol and β-cyclodextrin was confirmed by molecular docking. Hence, the SC β-cyclodextrin-myrtenol complex was evaluate for its anti-hyperalgesic, anxiolytic and antioxidant activity in a fibromyalgia model. Results show that myrtenol and β-cyclodextrin form a stable complex and have anti-hyperalgesic effect, improve the cognitive impairment caused and have an anxiolytic-like effect. Furthermore, the β-cyclodextrin/myrtenol complex decrease lipoperoxidation, increased catalase activity and a reduce SOD/CAT ratio. Therefore, β-cyclodextrin/myrtenol complex reduce painful behavior, improves motor skills and emotional behavior and decreases oxidative stress in a fibromyalgia model.

Topics: Animals; Antioxidants; beta-Cyclodextrins; Bicyclic Monoterpenes; Chronic Pain; Cognitive Dysfunction; Fibromyalgia; Hyperalgesia; Male; Mice; Musculoskeletal Pain; Nociceptive Pain

Due to its unclear pathophysiology, the pharmacological treatment of fibromyalgia is a challenge for researchers. Studies using medicinal plants, such as those from the genus Lippia, complexed with cyclodextrins (CDs) have shown innovative results.. The present research intended to evaluate the effect of an inclusion complex containing β-cyclodextrin (βCD) inclusion complex with Lippia grata (LG) essential oil in a chronic musculoskeletal pain model, its central activity and its possible interaction with neurotransmitters involved in pain.. After acid saline-induced chronic muscle pain, male mice were evaluated for primary and secondary hyperalgesia and muscle strength. Moreover, an antagonist assay was performed to assess the possible involvement of the opioidergic, serotonergic and noradrenergic pathways. In addition, Fos protein in the spinal cord was assessed, and a docking study and antioxidant assays were performed.. The treatment with LG-βCD, especially in the dose of 24mg/kg, was able to significantly decrease (p<0.05) the paw withdrawal and muscle threshold. Furthermore, LG-βCD was shown to affect the opioidergic and serotonergic pathways. There were no significant changes in muscle strength. Fos protein immunofluorescence showed a significant decrease in expression in the dorsal horn of the spinal cord. The main compounds of LG showed through the docking study interaction energies with the alpha-adrenergic and μOpioid receptors. In all antioxidant assays, LG exhibited stronger antioxidant activities than LG-βCD.. This study suggested that LG-βCD could be considered as a valuable source for designing new drugs in the treatment of chronic pain, especially musculoskeletal pain.

Topics: Analgesics; Animals; Antioxidants; beta-Cyclodextrins; Chronic Pain; Disease Models, Animal; Hyperalgesia; Lippia; Male; Methysergide; Mice; Molecular Docking Simulation; Musculoskeletal Pain; Naloxone; Oils, Volatile; Plant Leaves; Proto-Oncogene Proteins c-fos; Spinal Cord Dorsal Horn; Yohimbine

Chronic musculoskeletal pain is one of the main symptoms found in Fibromyalgia with unclear etiology and limited pharmacological treatment. The aim of this study was to complex LIM in β-cyclodextrin (LIM-βCD) and then evaluate its antihyperalgesic effect in an animal model of chronic musculoskeletal pain. Differential scanning calorimetry and scanning electron microscopy was used for the characterization of the inclusion complex. Male Swiss mice were used for experimental procedures where mechanical hyperalgesia, thermal hyperalgesia, muscular strength, Fos immunofluorescence was studied after induction of hyperalgesia. Mechanism of action was also investigated through tail flick test and capsaicin-induced nociception. Endothermic events and morphological changes showed that the slurry complex method was the best method for the complexation. After induction of hyperalgesia, the oral administration of LIM-βCD (50mg/kg) significantly increased the paw withdrawal threshold compared to uncomplexed limonene. Fos immunofluorescence showed that both compounds significantly decreased the number of Fos-positive cells in the dorsal horn. In nociceptive tests, FLU was able to reverse the antinociceptive effect of LIM-βCD. After intraplantar administration of capsaicin, LIM was able to significantly decrease time to lick. LIM-βCD has antihyperalgesic action superior to its uncomplexed form, with possible action in the dorsal horn of the spinal cord. These results suggest the possible applicability of LIM, uncomplexed or complexed with βCD, in conditions such as FM and neuropathic pain, for which there are currently only limited pharmacological options.

Topics: Analgesics; Animals; beta-Cyclodextrins; Capsaicin; Cyclohexenes; Disease Models, Animal; Drug Combinations; Drug Interactions; GABA Agents; Hyperalgesia; Limonene; Male; Mice; Muscle Strength; Musculoskeletal Pain; Nociception; Pain Measurement; Pain Threshold; Proto-Oncogene Proteins c-fos; Spinal Cord; Statistics, Nonparametric; Terpenes