Copaiba oleoresin has topical antinociceptive activity in a UVB radiation-induced skin-burn model in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Copaiba oleoresin, extracted from Copaifera L., is used as a wound healing, analgesic, antimicrobial and, mainly, anti-inflammatory agent. Thus, in this study we investigated the antinociceptive and anti-inflammatory effects of a topical formulation containing Copaiba oleoresin (3%) in a UVB radiation-induced skin burn model (0.75 J/cm2) in mice and performed a cream-formulation stability study. MATERIALS AND METHODS: The chemical composition of Copaiba oleoresin was analyzed using gas chromatography (GC-MS). The topical antinociceptive (evaluated through mechanical allodynia and thermal hyperalgesia) and the anti-inflammatory (dermal thickness and inflammatory cell infiltration) effects of treatments were assessed. The cream-formulation stability study was performed after two months, and organoleptic characteristics, pH, spreadability and rheological characteristics were analyzed. RESULTS: Copaiba oleoresin cream was able to prevent UVB radiation-induced mechanical allodynia on the 2nd, 3rd and 4th day after UVB radiation exposure with a maximum inhibition (Imax) of 64.6 ± 7% observed on the 2nd day; it also reduced the thermal hyperalgesia on the 1st and 2nd days post UVB radiation, with a Imax of 100% observed on the 2nd day. Moreover, topical treatment with Copaiba oleoresin cream inhibited the inflammatory cell infiltration, but did not reduce the dermal thickness. Such effects can be attributed, at least in part, to the presence of biological components, such as ß-caryophyllene and other sesquiterpenes identified by GC-MS. CONCLUSION: Our results demonstrate that the topical formulation containing Copaiba oleoresin presented antinociceptive and anti-inflammatory effects in mice subjected to a UVB radiation and that the cream-formulation was stable for two months. Thus, use of Copaiba oleoresin is a promising strategy for the treatment of inflammatory pain associated with sunburn.

TRPA1 involvement in analgesia induced by Tabernaemontana catharinensis ethyl acetate fraction in mice.

BACKGROUND: Ionic channels such as the transient receptor potential ankyrin 1 (TRPA1) are essential for the detection and transmission of painful stimuli. In this sense, new TRPA1 antagonists have been searched as analgesics. PURPOSE: Preclinical studies support the antinociceptive activity of Tabernaemontana catharinensis ethyl acetate fraction (Eta), which has constituents previously identified as TRPA1 antagonists (gallic acid). It was verified for the first time the involvement of the TRPA1 on Eta's antinociceptive and anti-inflammatory effects in mice pain models. STUDY DESIGN: It was evaluated the Eta's effect (0.01-100 mg/kg, oral route) on nociceptive (spontaneous nociception, mechanical and cold allodynia) and inflammatory (paw edema) parameters in pain models involved with TRPA1 activation. METHODS: Firstly, it was investigated the ability of Eta to act on TRPA1 or TRPV1 channels (Ca2+influx and binding assays in mice spinal cords). Next, it was evaluated the Eta's antinociceptive and anti-inflammatory effects after intraplantar injection of TRPA1 agonists (hydrogen peroxide, cinnamaldehyde or allyl isothiocyanate) in male Swiss mice (30-35 g). Moreover, the Eta's antinociceptive effects were evaluated on complete Freund's adjuvant (CFA)-induced chronic inflammatory pain (CIP), postoperative pain and on paclitaxel-induced peripheral neuropathy (PIPN). Oxidative parameters were evaluated in mice paw utilized for CFA induced-CIP model. RESULTS: Eta inhibited the TRPA1 agonist-induced Ca2+ influx [Imax = 72.4 ±â€¯1.5%; IC50 = 0.023(0.004-0.125)µg/ml], but not TRPV1 agonist-induced, nor was able to displace [3H]-resiniferatoxin (TRPV1 agonist) binding. Eta (0.1-100 mg/kg) inhibited the spontaneous nociception [ID50 = 0.043(0.002-0.723)mg/kg], mechanical [ID50 = 7.417(1.426-38.570)mg/kg] and cold allodynia, and edema development caused by TRPA1 agonists. Moreover, Eta (100 mg/kg) prevented and reversed the CFA-induced CIP (Imax = 55.8 ±â€¯13.7%, Imax = 80.4 ±â€¯5.1%, respectively) and postoperative pain (Imax = 88.0 ±â€¯11.6%, Imax = 51.3 ±â€¯14.9%, respectively), been also effective in reversing the acute (Imax = 94.4 ±â€¯12.4%) and chronic (Imax = 86.8 ±â€¯8.6%) PIPN. These effects seem to occur by TRPA1 channels pathway, and independently of TRPV1 or oxidative mechanisms. CONCLUSION: Our results demonstrate that Eta-induced antinociception and anti-inflammatory effects occur by TRPA1 inhibition making possible the use of this preparation as a potential therapeutic agent to treat pathological pains.

Citrus essential oils inhalation by mice: Behavioral testing, GCMS plasma analysis, corticosterone, and melatonin levels evaluation.

The use of orange essential oils (EOs) as a complementary treatment is very common in Brazilian popular culture. The levels of melatonin (MEL) and corticosterone (CORT) hormones were investigated simultaneously, by the Luminex™ immunoassay system in mice plasma, after Citrus aurantium and Citrus sinensis EOs inhalation for 30 min. The plasma was analyzed by headspace through gas chromatography coupled to mass spectrometry for investigation of the EO components. Mice were submitted to behavioral testing to research anxiolytic-like, sedative, and antidepressant-like effects. The inhalation of atmosphere obtained from vaporization of 10% solution of this Citrus EO separately did not affect MEL or CORT plasma levels; that is, the MEL and CORT levels did not present variation in function of the EO in the schedule used. On the other hand, the imipramine positive control used altered the level of MEL as expected. The EO constituents were detected in plasma at different ratios that is present in inhaled EO. Behavioral tests showed that the inhalation of 10% C. sinensis EO presents an anxiolytic-like and sedative effect. Thus, C. sinensis EO can be a valuable tool for treatment of the anxiety disturbs, apparently without interference with MEL and CORT physiological levels.