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

2019; Elsevier BV; Volume: 61; Linguagem: Inglês

10.1016/j.phymed.2019.152836

1618-095X

Wagner Barbosa da Rocha Santos, Marlange Almeida Oliveira Melo, Rafael S. Alves, Renan Guedes de Brito, Thallita Kelly Rabelo, Lindaura da S. Prado, Virgínia Kelma dos Santos Silva, Daniel P. Bezerra, José Evaldo Rodrigues de Menezes‐Filho, Diego Santos Souza, Carla Maria Lins de Vasconcelos, Luciana Scotti, Luciana Scotti, Waldecy de Lucca Júnior, Lucindo José Quintans‐Júnior, Adriana Gibara Guimarães,

Ion channel regulation and function

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.PC has antinociceptive effect in a model of oncologic pain due to the activation of the descending inhibitory pathway of pain.A pre-clinical, longitudinal, blind and randomized study.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 Ca2+ currents (electrophysiological records), histological and neurochemical changes (immunofluorescence for Fos) were also evaluated.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).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.