Cyclodextrin-complexed Ocimum basilicum leaves essential oil increases Fos protein expression in the central nervous system and produce an antihyperalgesic effect in animal models for fibromyalgia.

O. basilicum leaves produce essential oils (LEO) rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. ß-Cyclodextrin (ß-CD) has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in ß-CD (LEO/ß-CD), on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/ß-CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.) or vehicle (saline), and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey), motor coordination (Rota-rod) and muscle strength (Grip Strength Metter) in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC), thermogravimetry/derivate thermogravimetry (TG/DTG) and infrared absorption spectroscopy (FTIR) curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-ßCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with ß-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia.

Correlations between brain changes and pain management after cognitive and meditative therapies: A systematic review of neuroimaging studies.

BACKGROUND: There are different ways of dealing with pain and cognitive and meditative therapies (CMT) are alternative ways to regulate the emotions associated with pain. Current studies apply neuroimaging techniques trying to elucidate the neural mechanisms of cognitive strategies for pain. This systematic review aimed to summarize the evidence on brain activity changes after CMT, which include cognitive behavioral therapy, mindfulness and/or meditation, for pain management as well as to evaluate clinical pain outcomes. METHODS: Electronic databases - Pubmed, EMBASE, PsycINFO, Science Direct, Scopus - were searched to find randomized controlled trials (RCTs) examining neuroimaging data of CMT for chronic pain patients or healthy individuals with experimental pain. Two reviewers independently selected the relevant trials, rated for quality assessment and extracted all data using a standardized form. Primary outcome was brain activity changes (activation, deactivation or functional connectivity). Secondary outcomes were pain intensity, self-management, pain coping, quality of life, anxiety and depression. RESULTS: Nine RCTs were included involving 280 adults (18-59 years), 139 chronic pain patients vs. 148 healthy subjects. Three main kinds of intervention were identified: cognitive-behavioral therapy (n = 4), mindfulness meditation (n = 4) and transcendental meditation technique (n = 1). Neuroimaging results revealed distinct patterns of activity, but the main findings were related to increased activation of prefrontal cortex (PFC), specially dorsolateral prefrontal cortex (dlPFC) and ventrolateral prefrontal cortex (vlPFC), orbitofrontal cortex (OBF), somatosensory cortices (SSC) and limbic system in chronic pain population; and increased activation of anterior cingulate cortex (ACC), anterior insular cortex (AI) and decreased activation of thalamus in healthy individuals following CMT. CONCLUSION: This result means that regulation of pain by CMT can alter functioning of brain regions in an extensive network including non-nociceptive regions. CMT reduced the affective experience of pain, while reductions of pain intensity ratings were less consistent. Brain changes have been demonstrated as a result of the application of psychological measures and may represent the clinical implications of changes in brain activity or morphology.

Linalool and linalool complexed in ß-cyclodextrin produce anti-hyperalgesic activity and increase Fos protein expression in animal model for fibromyalgia.

The analgesic activity of (-)-linalool (LIN), a monoterpene present in essential oils of Lamiaceae species, has been previously demonstrated in rodents. However, its possible use in the treatment of fibromyalgia (FM) was never demonstrated. Additionally, as a short half-life is a limitation for the LIN medicinal application, the employment of drug delivery systems has been used to improve pharmaceutical properties of this compound. We investigated the anti-nociceptive effect of LIN, isolated or in ß-cyclodextrin complex (LIN-CD), in an animal model of chronic non-inflammatory muscle pain (a FM animal model), as well as its effect on the central nervous system (CNS). Male Swiss mice were subjected to two injections of acidic saline (pH 4; 20 µL/gastrocnemius) and were treated on alternate days, with LIN-CD (25 mg/kg, p.o.), LIN (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.), or vehicle (neutral saline). After 60 min, they were screened for mechanical hyperalgesia (von Frey), motor coordination (rotarod), and muscle strength (grip strength meter) for 27 days. The CNS areas involved in the anti-hyperalgesic activity were evaluated by immunofluorescence. LIN or LIN-CD produced a significant reduction (p < 0.001) of mechanical hyperalgesia on chronic non-inflammatory muscle pain model, which remained for 24 h only in LIN-CD, and these compounds significantly (p < 0.05) activated neurons of the locus coeruleus, nucleus raphe magnus, and periaqueductal gray areas. So, our results suggest that LIN-CD improved analgesic profile of LIN, with a probable involvement of descending pain pathways and the anti-nociceptive effect of linalool in an animal model of chronic non-inflammatory muscle pain. So far, only the investigations in animal models of inflammatory pain and supraspinatus were published.