Cannabidiol and endogenous opioid peptide-mediated mechanisms modulate antinociception induced by transcutaneous electrostimulation of the peripheral nervous system

• Published in: Journal of the neurological sciences 2014-12, Vol.347 (1), p.82-89
• Main Authors: Gonçalves, Thais Cristina Teixeira, Londe, Anna Karla, Albano, Rafael Isaac Pires, de Araújo Júnior, Artur Teixeira, de Aguiar Azeredo, Mariana, Biagioni, Audrey Francisco, Vasconcellos, Thiago Henrique Ferreira, dos Reis Ferreira, Célio Marcos, Teixeira, Dulcinéa Gonçalves, de Souza Crippa, José Alexandre, Vieira, Débora, Coimbra, Norberto Cysne
• Format: Article
• Language: English
• Subjects: Animals; Cannabidiol; Cannabidiol - metabolism; Cannabidiol - pharmacology; Diazepam - pharmacology; Endogenous opioid peptides; GABAA receptor; Hypnotics and Sedatives - pharmacology; Male; Naloxone - pharmacology; Narcotic Antagonists - pharmacology; Neurology; Nociceptive Pain - metabolism; Nociceptive Pain - therapy; Opioid Peptides - drug effects; Opioid Peptides - metabolism; Pain; Pain Measurement; Peripheral nervous system; Peripheral Nervous System - drug effects; Peripheral Nervous System - physiology; Rats; Rats, Wistar; Transcutaneous Electric Nerve Stimulation - methods; Transcutaneous electrical stimulation
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2014.09.024

Abstract Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological therapy for the treatment of pain. The present work investigated the effect of cannabidiol, naloxone and diazepam in combination with 10 Hz and 150 Hz TENS. Male Wistar rats were submitted to the tail-flick test (baseline), and each rodent received an acute administration (intraperitoneal) of naloxone (3.0 mg/kg), diazepam (1.5 mg/kg) or cannabidiol (0.75 mg/kg, 1.5 mg/kg, 3.0 mg/kg, 4.5 mg/kg, 6.0 mg/kg and 12.0 mg/kg); 10 min after the acute administration, 10 Hz or 150 Hz TENS or a sham procedure was performed for 30 min. Subsequently, tail-flick measures were recorded over a 90-min period, at 5-min intervals. 10 Hz TENS increased the nociceptive threshold during the 90-min period. This antinociceptive effect was reversed by naloxone pre-treatment, was not altered by diazepam pre-treatment and was abolished by cannabidiol pre-treatment (1.5 mg/kg). Moreover, 150 Hz TENS increased tail-flick latencies by 35 min post-treatment, which was partially inhibited by naloxone pre-treatment and totally inhibited by cannabidiol (1.5 mg/kg). These data suggest the involvement of the endogenous opioid system and the cannabinoid-mediated neuromodulation of the antinociception induced by transcutaneous electrostimulation at 10 Hz and 150 Hz TENS.