Evidence for the involvement of descending pain-inhibitory mechanisms in the attenuation of cancer pain by carvacrol aided through a docking study

Guimarães, Adriana Gibara; Scotti, Luciana; Júnior, Francisco Jaime Bezerra Mendonça; Melo, Nayara S.R.; Alves, Rafael S.; Júnior, Waldecy de Lucca; Bezerra, Daniel P.; Gelain, Daniel Pens; Quintans‐Júnior, Lucindo José

doi:10.1016/j.lfs.2014.08.020

Cited by 36 publications

(18 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These have been associated with the sensitization of specific fibers, such as an increase in the suprathreshold response of C and A-δ in hyperalgesia, a sensitization of C-fiber nociceptors in spontaneous nociception and allodynia through a lower threshold of the A-β fibers. The findings herein reported corroborate with the results described by Guimarães et al, 2014a. Previous studies demonstrated that PC presents a proven anti-inflammatory and analgesic pharmacological profile in models of acute and orofacial pain (Bonjardim et al, 2012; de…”

Section: [Insert Fig 1]supporting

confidence: 91%

“…Cells obtained from the ascitic fluid were then analyzed in Neubauer's chamber for the assessment of the percentage of viable cells using Trypan blue solution 1%. A suspension of these tumor cells containing 10 6 cells in 25 μl was implanted in the right hind paw of the mice following a previous protocol (Gouveia et al, 2018;Guimarães et al, 2014aGuimarães et al, , 2015.…”

Section: Tumor Cell and Implantationmentioning

confidence: 99%

“…Mice were evaluated for the sensitivity towards mechanical stimulation by Von Frey's test (electronic anesthesiometer, EFF-301 model, Insight®, Brazil) on the tumor-bearing paw. This stimulation causes a hind limb lifting reflex that corresponds to the paw withdrawal followed by clear movements of flinches (Guimarães et al, 2014a). The intensity of stimulus was obtained by averaging four measurements performed with minimal intervals of 3 min.…”

Section: Mechanical Hyperalgesiamentioning

confidence: 99%

See 2 more Smart Citations

p-Cymene attenuates cancer pain via inhibitory pathways and modulation of calcium currents

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background: Oncological pain is one of the most prevalent and difficult-to-treat symptoms in patients with cancer. p-cymene (PC) is a monoterpene found in more than 100 different plant species, endowed with various pharmacological properties-particularly antinociceptive. Hypothesis/Purpose: PC has antinociceptive effect in a model of oncologic pain due to the activation of the descending inhibitory pathway of pain. Study Design: A pre-clinical, longitudinal, blind and randomized study. Methods: Male Swiss mice were induced with S180 cells in the right hind paw, then treated daily with PC (12.5, 25 and 50 mg/kg, s.c.) and screened for mechanical hyperalgesia, spontaneous nociception, nociception induced by non-noxious palpation, tumor growth, changes in the neuromuscular function and existence of bone degradation in the tumor area. The effect of PC on Ca 2+ currents (electrophysiological records), histological and neurochemical changes (immunofluorescence for Fos) were also evaluated. Results: PC reduced (p < 0.05) the mechanical hyperalgesia, the spontaneous (p < 0.001) and non-noxious palpation (p < 0.001) nociceptions, not changing the tumor development, neuromuscular function or histopathological aspects of the paw affected. PC reduced Fos expression in the spinal cord (p < 0.001) and increased this expression in the PAG (p < 0.05) and in the NRM (p < 0.01). PC decreased the density of calcium channel currents (p < 0.05). Conclusion: These results suggest the antinociceptive effect of PC on oncologic pain, probably acting in both ascending and descending pain pathways, and modulating the calcium channel currents in order to exert its effects.

show abstract

Section: [Insert Fig 1]supporting

confidence: 91%

Section: Tumor Cell and Implantationmentioning

confidence: 99%

Section: Mechanical Hyperalgesiamentioning

confidence: 99%

See 1 more Smart Citation

p-Cymene attenuates cancer pain via inhibitory pathways and modulation of calcium currents

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…In a study on mice, CV showed 66.4% reduction in hyperalgesia, besides significantly reducing the paw volume with average inhibition percentages of 42.0% (Guimarães et al, 2014). Carvacrol has several mechanisms of action, especially in neuromodulation, acting on the brain nuclei such as the periaqueductal gray, nucleus raphe magnus, and locus coeruleus, via γ-aminobutyric acid receptors.…”

Section: In Vivo Studiesmentioning

confidence: 99%

Carvacrol and human health: A comprehensive review

Sharifi‐Rad

Varoni

Iriti

et al. 2018

Phytotherapy Research

414

261

View full text Add to dashboard Cite

Carvacrol (CV) is a phenolic monoterpenoid found in essential oils of oregano (Origanum vulgare), thyme (Thymus vulgaris), pepperwort (Lepidium flavum), wild bergamot (Citrus aurantium bergamia), and other plants. Carvacrol possesses a wide range of bioactivities putatively useful for clinical applications such antimicrobial, antioxidant, and anticancer activities. Carvacrol antimicrobial activity is higher than that of other volatile compounds present in essential oils due to the presence of the free hydroxyl group, hydrophobicity, and the phenol moiety. The present review illustrates the state-of-the-art studies on the antimicrobial, antioxidant, and anticancer properties of CV. It is particularly effective against food-borne pathogens, including Escherichia coli, Salmonella, and Bacillus cereus. Carvacrol has high antioxidant activity and has been successfully used, mainly associated with thymol, as dietary phytoadditive to improve animal antioxidant status. The anticancer properties of CV have been reported in preclinical models of breast, liver, and lung carcinomas, acting on proapoptotic processes. Besides the interesting properties of CV and the toxicological profile becoming definite, to date, human trials on CV are still lacking, and this largely impedes any conclusions of clinical relevance.

show abstract

“…According to Guimarães et al (2014), negative ΔG bind values represent favorable interactions of the ligand-receptor complex. The molecular docking interactions in Table 3 demonstrated that UA had lower binding energies with the NMDA receptor subunits GluN1a (−7.02 kcal/mol), GluN2B (−5.69 kcal/mol) and COX-2 (−9.89 kcal/mol).…”

Section: Discussionmentioning

confidence: 99%

Antinociceptive Activity of Borreria verticillata: In vivo and In silico Studies

et al. 2017

View full text Add to dashboard Cite

Borreria verticillata (L.) G. Mey. known vassourinha has antibacterial, antimalarial, hepatoprotective, antioxidative, analgesic, and anti-inflammatory, however, its antinociceptive action requires further studies. Aim of the study evaluated the antinociceptive activity of B. verticillata hydroalcoholic extract (EHBv) and ethyl acetate fraction (FAc) by in vivo and in silico studies. In vivo assessment included the paw edema test, writhing test, formalin test and tail flick test. Wistar rats and Swiss mice were divided into 6 groups and given the following treatments oral: 0.9% NaCl control group (CTRL), 10 mg/kg memantine (MEM), 10 mg/kg indomethacin (INDO), 500 mg/kg EHBv (EHBv 500), 25 mg/kg FAc (FAc 25) and 50 mg/kg FAc (FAc 50). EHBv, FAc 25 and 50 treatments exhibited anti-edematous and peripheral antinociceptive effects. For in silico assessment, compounds identified in FAc were subjected to molecular docking with COX-2, GluN1a and GluN2B. Ursolic acid (UA) was the compound with best affinity parameters (binding energy and inhibition constant) for COX-2, GluN1a, GluN2B, and was selected for further analysis with molecular dynamics (MD) simulations. In MD simulations, UA exhibited highly frequent interactions with residues Arg120 and Glu524 in the COX-2 active site and NMDA, whereby it might prevent COX-2 and NMDA receptor activation. Treatment with UA 10 mg/Kg showed peripheral and central antinociceptive effect. The antinociceptive effect of B. verticillata might be predominantly attributed to peripheral actions, including the participation of anti-inflammatory components. Ursolic acid is the main active component and seems to be a promising source of COX-2 inhibitors and NMDA receptor antagonists.

show abstract

Evidence for the involvement of descending pain-inhibitory mechanisms in the attenuation of cancer pain by carvacrol aided through a docking study

Abstract: Together, these results demonstrated that CARV may be an interesting option for the development of new analgesic drugs for the management of cancer pain.

Cited by 36 publications

References 34 publications

p-Cymene attenuates cancer pain via inhibitory pathways and modulation of calcium currents

p-Cymene attenuates cancer pain via inhibitory pathways and modulation of calcium currents

Carvacrol and human health: A comprehensive review

Antinociceptive Activity of Borreria verticillata: In vivo and In silico Studies

Contact Info

Product

Resources

About