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

Abstract

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.

Pharmacological Assessment of the Carvacrol Chemotype Essential Oil From Plectranthus amboinicus Growing in Cuba

“…Antiproliferative activity of other minor components has also been described. In this sense, antiprotozoal and/or anticancer effects of pcymene, γ-terpinene, terpinen-4-ol, β-caryophyllene 59,79,80 and caryophyllene oxide 62,81 have been described.…”

Antinociceptive Activity of Chemical Components of Essential Oils That Involves Docking Studies: A Review

“…Among the phytochemicals studied were a-Terpineol (Oliveira et al, 2016;Gouveia et al, 2018); 3-(5-substituted-1,3,4-oxadiazol-2-yl)-N′-[2-oxo-1,2-dihydro-3H-indol-3ylidene] propane hydrazide (Kerzare et al, 2016); b-cyclodextrin (CT-bCD) complexed with citronellal (CT) (Santos et al, 2016); (−)-a-bisabolol (Melo et al, 2017;Teixeira, et al, 2017); bcyclodextrin complexed with farnesol (Silva et al, 2017), and p-Cymene (Santos et al, 2019).…”

“…Assis et al (Santos et al, 2016;Gouveia et al, 2018Santos et al, 2019. The in silico programs used for docking studies were; Molegro Virtual Docker (Oliveira et al, 2016;Siqueira-Lima et al, 2017;de Oliveira Juńior et al, 2018;Gouveia et al, 2018;Leite et al, 2019;Santos et al, 2019); Sybyl ® X software suite (Garcıá et al, 2011), Vlife MDS (Kerzare et al, 2016); AutoDock Vina (Santos et al, 2016); Hex Protein Docking (HEX) (Teixeira et al, 2017;Melo et al, 2017); and AutoDock 4.2 software in PyRx 0.9 (Silva et al, 2017).…”

“…The molecular targets/complexes used in the docking studies were Nitric Oxide Synthase (Gouveia et al, 2018), COX-2 (Garcıá et al, 2011;Sumiwi et al, 2015;Kerzare et al, 2016); GluR2-S1S2 (Santos et al, 2016); TRPV1 (Teixeira et al, 2017;Melo et al, 2017); b-CD complex (Silva et al, 2017); CaV1, CaV2.1, CaV2.2, and CaV2.3 (Santos et al, 2019); 5-HT receptor, Delta receptor, Kappa receptor, and MU (µ) receptor (Oliveira et al, 2016); Alpha Adrenergic, Opioid, and Serotonergic receptors (Siqueira-Lima et al, 2017); Muscarinic receptors and GABA A (De Oliveira Junior et al, 2017; de Oliveira Juńior et al, 2018); Opioid and Serotonin receptors (Quintans-Junior et al, 2018); 5-HT 3 and M2 receptors (Leite et al, 2019).…”

“…As a potential alternative to cancer-associated pain, Santos et al (2019) evaluated the effects of p-cymene on animal models of Sarcoma 180 (S180) induced nociception and investigated how it may act to promote such effect.…”