Search

Tagetes lucida Cav. is an ancient medicinal plant used to treat different ailments involving neurological diseases and pain. However, scientific studies to validate their medicinal properties as analgesic have not been described. The aim of this study was to evaluate the T. lucida antinociceptive response using pain models. Bioactive compounds and a possible mechanism of action were also explored. Dose-response effects of an ethanol crude extract were investigated in the writhing and formalin tests in mice and rats, respectively. The extract was fractionated to isolate active fractions and bioactive compounds (quercetagetin 7‑O‑β‑d‑glucoside and 6,7‑dimethoxycoumarin) using the formalin test. The antinociceptive effects were compared to the reference drugs (tramadol 10 mg/kg, diclofenac 50 mg/kg, and/or ketorolac 1 mg/kg, i.p.). The ethanol extract was explored in the presence of naloxone (3 mg/kg, i.p. a non-selective opioid receptor antagonist) and WAY100635 (0.5 mg/kg, s.c., a selective 5-HT 1A receptor antagonist) to screen their participation as possible inhibitory mechanisms involved in the antinociceptive response of T. lucida. The ethanol crude extract, fractions, and pure compounds caused a significant antinociceptive response resembling the effect of the reference drugs. Both opioid and 5-HT 1A receptors participated in the analgesic -like activity of the extract, which did not produce gastric damage. On the contrary, the gastric damage produced as an adverse effect of the analgesic ketorolac was prevented when combined with the extract. In conclusion, these preliminary data provide evidence and give support to the properties attributed to T. lucida in the traditional medicine to alleviate pain., (Copyright © 2019. Published by Elsevier Inc.)

In the current study a method for the probabilistic accounting of the water footprint (WF) at the river basin level has been proposed and developed. It is based upon the simulation of the anthropised water cycle and combines a hydrological model and a decision support system. The methodology was carried out in the Segura River Basin (SRB) in South-eastern Spain, and four historical scenarios were evaluated (1998-2010-2015-2027). The results indicate that the WF of the river basin reached 5581 Mm 3 /year on average in the base scenario, with a high variability. The green component (3231 Mm 3 /year), mainly generated by rainfed crops (62%), was responsible for the great variability of the WF. The blue WF (1201 Mm 3 /year) was broken down into surface water (56%), renewable groundwater (20%) and non-renewable groundwater (24%), and it showed the generalized overexploitation of aquifers. Regarding the grey component (1150 Mm 3 /year), the study reveals that wastewater, especially phosphates (90%), was the main culprit producing water pollution in surface water bodies. The temporal evolution of the four scenarios highlighted the successfulness of the water treatment plans developed in the river basin, with a sharp decrease in the grey WF, as well as the stability of the WF and its three components in the future. So, the accounting of the three components of the WF in a basin was integrated into the management of water resources, it being possible to predict their evolution, their spatial characterisation and even their assessment in probabilistic terms. Then, the WF was incorporated into the set of indicators that usually is used in water resources management and hydrological planning., (Copyright © 2018 Elsevier B.V. All rights reserved.)

One of the main challenges in water management is to determine how the current water use can condition its availability to future generations and hence its sustainability. This study proposes the use of the Water Footprint (WF) indicator to assess the environmental sustainability in water resources management at the river basin level. The current study presents the methodology developed and applies it to a case study. The WF is a relatively new indicator that measures the total volume of freshwater that is used as a production factor. Its application is ever growing in the evaluation of water use in production processes. The calculation of the WF involves water resources (blue), precipitation stored in the soil (green) and pollution (grey). It provides a comprehensive assessment of the environmental sustainability of water use in a river basin. The methodology is based upon the simulation of the anthropised water cycle, which is conducted by combining a hydrological model and a decision support system. The methodology allows the assessment of the environmental sustainability of water management at different levels, and/or ex-ante analysis of how the decisions made in water planning process affect sustainability. The sustainability study was carried out in the Segura River Basin (SRB) in South-eastern Spain. The SRB is among the most complex basins in Europe, given its special peculiarities: competition for the use, overexploitation of aquifers, pollution, alternative sources, among others. The results indicate that blue water use is not sustainable due to the generalised overexploitation of aquifers. They also reveal that surface water pollution, which is not sustainable, is mainly caused by phosphate concentrations. The assessment of future scenarios reveals that these problems will worsen if no additional measures are implemented, and therefore the water management in the SRB is environmentally unsustainable in both the short- and medium-term., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The administration of dopaminergic drugs produces analgesia in individuals experiencing different types of pain. Analgesia induced by these drugs at the spinal cord level is mediated by D2-like agonists, which specifically inhibit the detection of nociceptive stimuli by sensory afferents. The extent of the analgesia provided by spinal dopamine agonists remains controversial, and the cellular mechanism of this analgesic process is poorly understood. The objective of this study was to evaluate the analgesic effect of quinpirole, a D2-like agonist, based on two nociceptive tests and at various doses that were selected to specifically activate dopamine receptors. We found that intrathecal quinpirole administration produces analgesia of mechanical but not thermal nociception and that the analgesic effect of quinpirole is reversed by a mix of D2, D3, and D4 receptor-specific antagonists, suggesting that the activation of all D2-like receptors is involved in the analgesia produced by intrathecal quinpirole. The differential effect on thermal and mechanical nociception was also tested upon the activation of μ-opioid receptors. As reported previously, low doses of the μ-opioid receptor agonist DAMGO produced analgesia of only thermonociception. This evidence shows that a D2-like receptor agonist administered at the spinal cord level produces analgesia specific to mechanonociception but not thermonociception., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: In order to explore the potential role of GABA, acetylcholine and glutamate in the caudo-lateral peribrachial area (C-PBL) over Rapid-Eye-Movement sleep (REM) onset and maintenance as well as on synchronized sleep with ponto-geniculo-occipital (PGO) waves (SP) in cats, a muscimol, carbachol and L-glutamate local application was performed and behavioral states were assessed., Methods: Fourteen chronically implanted, adult, male cats underwent a 23 hour polysomnographic recording after 3 pharmacological manipulations: carbachol, muscimol and L-glutamate. Each cat received all three drugs randomly with a seven day interval., Results: 1) Carbachol increases waking, SP and REM sleep while decreases slow wave sleep (SWS). 2) Muscimol decreases SP percentage and number while increases REM sleep onset. 3) Carbachol facilitates PGO activity and increases the latency to both SWS1 and REM sleep but enhances PGO activity while muscimol decreases it., Conclusions: Acetylcholine promotes PGO related states (SP as well as REM sleep), while GABA reduces only SP and specifically PGOs., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Agastache mexicana is a plant that has long been used in large demands in Mexican folk medicine to treat anxiety, insomnia and pain, among others affections. Chromatographic technique was used to identify ursolic acid (UA), 130.7 mg/g and 20.3 mg/g, as an antinociceptive active compound identified in ethyl acetate and methanol extracts of A. mexicana aerial parts, respectively. Temporal course curves of the antinociceptive response demonstrated a dose-dependent and significant activity of UA (1 to 100 mg/kg, i.p.) with an ED50=2 mg/kg in comparison to the efficacy of diclofenac (1 or 30 to 100 mg/kg, i.p.), a non-steroidal anti-inflammatory drug, with an ED50=11.56 mg/kg. The antinociceptive response consisted in the reduction of abdominal constrictions induced with 1% acetic acid in mice. Similarly, UA at 2 mg/kg produced significant antinociception in the intracolonic administration of 0.3% capsaicin (a TRPV1 agonist) in mice. It has been reported the inhibition produced by UA on the calcium-flux induced by capsaicin on TRPV1 receptor suggesting the antagonistic activity of this receptor. Finally, an ED50=44 mg/kg was calculated in the neurogenic and inflammatory nociception induced in the formalin test in rats. The antinociceptive response of UA in the formalin test was not modified in presence of naloxone, flumazenil or L-arginine. Nevertheless, it was reverted in presence of 1-H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, an inhibitor of soluble guanylyl cyclase) and increased in presence of N(G)-L-nitro-arginine methyl ester (L-NAME, inhibitor of nitric oxide synthase), theophylline (inhibitor of phosphodiesterase) and WAY100635 (an antagonist of 5-HT1A receptors). Current results provide evidence that the antinociceptive response of A. mexicana depends in part on the presence of UA. Moreover, this triterpene may exerts its antinociceptive effect mediated by the presence of cGMP and an additive synergism with 5HT1A receptors, but also an antagonistic activity towards TRPV1 receptors may be involved., (© 2013.)

Hesperidin occurs in greatest concentration in plants from the Rutaceae and Lamiaceae families. In human nutrition it contributes to the integrity of blood vessels and its deficiency in the diet has been linked to abnormal capillary leakiness as well as pain. In this study, the bioflavonoid hesperidin was identified as an active compound in an ethanol extract of the Rosmarinus officinalis aerial parts tested in the pain-induced functional impairment model in the rat (PIFIR) as an assay of inflammatory and chronic nociception similar to that observed in clinical gout. Hesperidin produced a dose-dependent and significant response with an ED₂₅=1666.72 mg/kg in comparison to an ED₂₅=302.90 mg/kg for the extract or an ED₂₅=0.47 mg/kg for the reference drug ketorolac in the PIFIR model. Although the antinociceptive response of R. officinalis was reverted in presence of the opioid antagonist naloxone (10 mg/kg, s.c.) and the 5HT(1A) antagonist WAY100635 (0.12 mg/kg, s.c.), the hesperidin response was not modified by naloxone (10 mg/kg), WAY100635 (0.12 mg/kg), bicuculline (1 mg/kg, s.c.), flumazenil (10 mg/kg, i.p.) or caffeine (1 mg/kg, s.c.). Nevertheless, it was reduced in presence of capsazepine (10 or 20 mg/kg, s.c.) suggesting the participation of the TRPV1 receptor, which was reinforced when hesperidin significantly reduced the capsaicin-induced nociceptive response. A synergistic interaction was also observed when antinociceptive doses of hesperidin were combined with those of ketorolac producing 15 combinations mainly in additive and supra-additive responses. These results provide evidence for the antinociceptive activity of hesperidin and demonstrate synergistic response when combined with ketorolac, possibly by involvement of the TRPV1 receptor, suggesting their clinical potential in pain therapy., (© 2010 Elsevier Inc. All rights reserved.)

Annonas are consumed as fresh fruits, but are also widely used in folk medicine for treating pain and other ailments. Antinociceptive properties of the Annona diversifolia ethanol crude extract were tested using the pain-induced functional impairment model in rat (PIFIR) and the writhing test in mice. The ethanol extract caused a 25% recovery of limb function in rats; this response was significant and dose-dependent. Furthermore, this extract produced a similar antinociceptive response (ED(50)=15.35 mg/kg) to that of the reference drug tramadol (ED(50)=12.42 mg/kg) when evaluated in the writhing test in mice. Bio-guided fractionation yielded hexane and acetone active fractions from which the presence of palmitone and flavonoids was respectively detected. Palmitone produced an antinociceptive response with an ED(50)=19.57 mg/kg in the writhing test. Antinociceptive responses from ethanol extract and tramadol were inhibited in the presence of either naloxone (1mg/kg, s.c.)--an antagonist of endogenous opioids--or WAY100635 (0.8 mg/kg, s.c.)--a 5-HT(1A) serotonin receptor antagonist. These results provide evidence that A. diversifolia possesses antinociceptive activity, giving support to their traditional use for treatment of spasmodic and arthritic pain. In addition, our results suggest the participation of endogenous opioids and 5-HT(1A) receptors in this antinociceptive response., ((c) 2009 Elsevier Inc. All rights reserved.)

The sustained inhibitory action of spinal endorphins could be responsible for the habituation of polysynaptic responses in the spinal cord. To test this hypothesis, acute spinalized unanesthetized cats (decerebrated and curarized) were used. Sural nerve electrical stimulation (0.2 Hz) was provided and a progressive decrease in the reflex response was found. Conversely, the field potential (lamina V) progressively increased during stimulation, reaching its maximum amplitude when ventral root response showed maximum habituation. The administration of naloxone (0.8-10.0 mg/kg) produced dehabituation or prevented habituation. The immunohistological results showed leu-enkephalin-like immunoreactive dot-like structures in close proximity to neurons of laminae VII, VIII and IX in the lumbo-sacral segment of the spinal cord. Our results suggest an involvement of opioid peptides in the habituation process.