Objectives: This paper aims to determine if hypnotic analgesia suggestion and transcranial direct-current stimulation (tDCS) have a differential effect on pain perception. We hypothesized that transcranial direct-current stimulation would be more effective than hypnotic analgesia suggestion at changing the descending pain modulating system, whereas the hypnotic suggestion would have a greater effect in quantitative sensory testing. Design: This is a randomized, double blind and crossover trial. Settings: All stages of this clinical trial were performed at the Laboratory of Pain and Neuromodulation of the Hospital de Clínicas de Porto Alegre. Subjects: Were included 24 healthy females aged from 18 to 45 years old, with a high susceptibility to hypnosis, according to the Waterloo-Stanford Group Scale of Hypnotic Susceptibility, Form C (15). Methods: The subjects received a random and crossover transcranial direct-current stimulation over the dorsolateral prefrontal cortex (2 mA for 20 min) and hypnotic analgesia (20 min). Results: Only hypnotic suggestion produced changes that are statistically significant from pre- to post-intervention in the following outcomes measures: heat pain threshold, heat pain tolerance, cold pressure test, and serum brain-derivate-neurotrophic-factor. The analysis showed a significant main effect for treatment ( F = 4.32; P = 0.04) when we compared the delta-(Δ) of conditioned pain modulation task between the transcranial direct-current stimulation and hypnotic suggestion groups. Also, the change in the brain-derivate-neurotrophic-factor was positively correlated with the conditioned pain modulation task. Conclusion: The results confirm a differential effect between hypnotic suggestion and transcranial direct-current stimulation on the pain measures. They suggest that the impact of the interventions has differential neural mechanisms, since the hypnotic suggestion improved pain perception, whereas the transcranial direct-current stimulation increased inhibition of the descending pain modulating system. Clinical Trial Registration: www.ClinicalTrials.gov , identifier NCT03744897. Perspective: These findings highlight the effect of hypnotic suggestion on contra-regulating mechanisms involved in pain perception, while the transcranial direct-current stimulation increased inhibition of the descending pain modulating system. They could help clinicians comprehend the mechanisms involved in hypnotic analgesia and transcranial direct-current stimulation and thus may contribute to pain and disability management.

Objective: We evaluated whether active(a)-tDCS combined with hypnotic analgesia suggestion (HS) would be more effective than a single active(a)-tDCS, and/or sham-(s)-tDCS and s-tDCS/HS on the following outcomes: function of descending pain modulatory system (DPMS) during the conditioned pain modulation test (CPM-test) (primary outcome), heat pain threshold (HPT), heat pain tolerance (HPTo) and cold pressor test (CPT) (secondary outcomes). We also examined whether their effects are related to neuroplasticity state evaluated by serum brain-derived-neurotropic factor (BDNF). Materials and Methods: Forty-eight females received one session of one of the four interventions (a-tDCS/HS, s-tDCS/HS, a-tDCS, and s-tDCS) in an incomplete randomized crossover sequence. The a-tDCS or s-tDCS was applied over the left dorsolateral prefrontal cortex (DLPFC) for 30 minutes at 2mA. Results: A generalized linear model revealed a significant main effect for the intervention group (P <0.032). The delta-(Δ) pain score on the Numerical Pain Scale (NPS0-10) during CPM-test in the a-tDCS/HS group was −0.25 (0.43). The (Δ) pain score on NPS (0-10) during CPM-test in the other three groups was a-tDCS=−0.54 (0.41), HS −0.01 (0.41) and s-tDCS/HS=−0.19 (0.43). A-tDCS/HS intervention increased the CPT substantially compared to all other interventions. Also, higher baseline levels of BDNF were associated with a larger change in CPT and HPTo. Conclusion: These findings indicate that the HS combined with a-tDCS mitigated the effect of the a-tDCS on the DPMS. The a-tDCS up-regulates the inhibition on DPMS, and the HS improved pain tolerance. And, together they enhanced the reaction time substantially upon the CPT. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03744897.