Y Baba1, H Kohase, Y Oono, K Fujii-Abe, L Arendt-Nielsen. 1. Section of Anesthesiology and Clinical Physiology, Division of Oral Health Science, Graduate school of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Abstract
BACKGROUND: Systemic administration of dexmedetomidine (DEX; selective α(2) -adrenoceptor agonist) is found to inhibit diffuse noxious inhibitory control in rats, now referred to as conditioned pain modulation (CPM) in humans. The present study was designed to investigate the effect of intravenous administration of DEX on CPM in humans. METHODS: There were two sequential sessions in this double blind, randomized study. The first session was the control with normal saline infusion (N(1st), L(1st), H(1st)). During the second session, three types of agents were infused: normal saline (N(2nd)); a low plasma concentration of DEX (0.04 ng/mL; L(2nd)); and a high plasma concentration of DEX (0.08 ng/mL; H(2nd)). The amplitude of somatosensory evoked potentials (ampSEP)s and the visual analogue scale of tooth pain (VASt) induced by electrical tooth stimulation were evaluated with and without conditioning CO(2) laser stimulation of the hand. The inhibition rate (% inhibition) was calculated [= (1-[ampSEP or VASt with conditioning stimuli]/[ampSEP or VASt without conditioning stimuli]) × 100] to compare the magnitude of the DEX effects on CPM. RESULTS: The inhibition rates of ampSEPs and VASt in Types N, L and H varied significantly, demonstrating a dose-dependent reduction of CPM effects of ampSEP and VASt during randomized DEX administration, consistent with results from animal studies. CONCLUSIONS: The present study shows that systemic administration of an α(2) -adrenoceptor agonist (DEX), less than the clinical dose, inhibited CPM in humans. These results may provide some mechanistic insight into why many chronic pain patients show impaired CPM.
RCT Entities:
BACKGROUND: Systemic administration of dexmedetomidine (DEX; selective α(2) -adrenoceptor agonist) is found to inhibit diffuse noxious inhibitory control in rats, now referred to as conditioned pain modulation (CPM) in humans. The present study was designed to investigate the effect of intravenous administration of DEX on CPM in humans. METHODS: There were two sequential sessions in this double blind, randomized study. The first session was the control with normal saline infusion (N(1st), L(1st), H(1st)). During the second session, three types of agents were infused: normal saline (N(2nd)); a low plasma concentration of DEX (0.04 ng/mL; L(2nd)); and a high plasma concentration of DEX (0.08 ng/mL; H(2nd)). The amplitude of somatosensory evoked potentials (ampSEP)s and the visual analogue scale of tooth pain (VASt) induced by electrical tooth stimulation were evaluated with and without conditioning CO(2) laser stimulation of the hand. The inhibition rate (% inhibition) was calculated [= (1-[ampSEP or VASt with conditioning stimuli]/[ampSEP or VASt without conditioning stimuli]) × 100] to compare the magnitude of the DEX effects on CPM. RESULTS: The inhibition rates of ampSEPs and VASt in Types N, L and H varied significantly, demonstrating a dose-dependent reduction of CPM effects of ampSEP and VASt during randomized DEX administration, consistent with results from animal studies. CONCLUSIONS: The present study shows that systemic administration of an α(2) -adrenoceptor agonist (DEX), less than the clinical dose, inhibited CPM in humans. These results may provide some mechanistic insight into why many chronic painpatients show impaired CPM.
Authors: Matheus Dorigatti Soldatelli; Timo Siepmann; Ben Min-Woo Illigens; Vinicius Souza Dos Santos; Iraci Lucena da S Torres; Felipe Fregni; Wolnei Caumo Journal: Br J Pain Date: 2020-05-30
Authors: Martin Gagné; Isabelle Côté; Mélanie Boulet; Catherine R Jutzeler; John L K Kramer; Catherine Mercier Journal: Neurorehabil Neural Repair Date: 2020-10-03 Impact factor: 3.919