Efeito do bloqueio do receptor serotoninérgico 5- HT3 sobre os limiares térmicos e mecânicos de dor e na modulação condicionada da dor em humanos

Abstract

Endogenous pain modulation is an umbrella term describing the succession of events that the central nervous system can use to reduce and, in some cases, increase sensitivity to pain. One form known as pain modulation is the phenomenon of inhibiting pain using a prior painful stimulus. The term CPM (conditioned pain modulation) is used to describe this phenomenon in humans. Serotonin pathways work as both anti- and pro-nociceptive pathways. There are questions about whether the use of serotonin antagonists, in people exposed to a nociceptive stimulus, can be a factor in increasing sensitivity to pain and compromising analgesic therapy. Ondansetron is a 5HT3 receptor antagonist routinely used to prevent postoperative nausea and vomiting. Therefore, this study’s objective was to evaluate ondansetron’s effect on mechanical and thermal pain thresholds, as well as CPM in humans. 17 volunteers, who were randomly selected and double blinded, participated in the research. They received an intravenous solution, containing 1 - NaCl at 0.9%, in a volume of 20 mL; 2 - NaCl at 0.9% and 8 mg ondansetron in a volume of 20 mL Before each intervention, the following basic tests were performed: Using the quantitative sensory test (QST), we obtained the thresholds for detecting warm and cold; pain thresholds to hot and cold; the pressure pain threshold. CPM was evaluated using the parallel paradigm in which two identical nociceptive test stimuli were induced before and simultaneous to a conditioned nociceptive stimulus (immersion of the contralateral hand in 46.5° C hot water for 60 seconds). After 30 minutes had passed following the intervention, we redid the tests. We repeated the tests one week later, but using the opposite solution, so that each participant was their own control (crossover). We used the Wilcoxon test to compare the variables. Our study demonstrated that ondansetron, administered intravenously, improved CPM (p = 0.02), in addition to increasing the heat detection threshold (p = 0,03) and lowering the cold detection threshold (p = 0.01). There were no influences on thermal and mechanical pain thresholds (p > 0,05). This study appears to be one of the first to investigate the role of ondansetron on thermal and mechanical pain thresholds and conditioned pain modulation in healthy humans, through quantitative sensory test. There is evidence that the results related to the antagonism of the 5HT-3 receptor by ondansetron, occur through inhibition of facilitating descending pathways, improving the CPM, without affecting thermal and mechanical pain thresholds. Further studies in humans with chronic pain should be conducted to assess the role of ondansetron as part of the therapeutic arsenal of painful conditions.