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Publication : D-limonene exhibits superior antihyperalgesic effects in a β-cyclodextrin-complexed form in chronic musculoskeletal pain reducing Fos protein expression on spinal cord in mice.

First Author  Araújo-Filho HG Year  2017
Journal  Neuroscience Volume  358
Pages  158-169 PubMed ID  28673718
Mgi Jnum  J:249750 Mgi Id  MGI:6092847
Doi  10.1016/j.neuroscience.2017.06.037 Citation  Araujo-Filho HG, et al. (2017) D-limonene exhibits superior antihyperalgesic effects in a beta-cyclodextrin-complexed form in chronic musculoskeletal pain reducing Fos protein expression on spinal cord in mice. Neuroscience 358:158-169
abstractText  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 beta-cyclodextrin (LIM-betaCD) 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-betaCD (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-betaCD. After intraplantar administration of capsaicin, LIM was able to significantly decrease time to lick. LIM-betaCD 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 betaCD, in conditions such as FM and neuropathic pain, for which there are currently only limited pharmacological options.
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