Abstract Introduction Fibromyalgia is a complex, generalized, and diffuse chronic musculoskeletal pain. Pharmacological approaches are widely used to relieve pain and increase quality of life. Low-Dose Naltrexone (LDN) was shown to increase the nociceptive threshold in patients with fibromyalgia. Transcranial Direct Current Stimulation (tDCS) is effective for pain management. Objective The purpose of this study was to evaluate the analgesic and neuromodulatory effects of a combination of LDN and tDCS in patients with fibromyalgia. Methods This was a randomized, double-blinded, parallel, placebo/sham-controlled trial (NCT04502251; RBR-7HK8N) in which 86 women with fibromyalgia were included, and written informed consent was obtained from them. The patients were allocated into four groups: LDN + tDCS (n = 21), LDN + tDCS Sham (n = 22), placebo + tDCS (n = 22), and placebo+tDCS Sham (n = 21). The LDN or placebo (p.o.) intervention lasted 26 days; in the last five sessions, tDCS was applied (sham or active, 20 min, 2 mA). The following categories were assessed: sociodemographic, Visual Analog Pain Scale (VAS), Pain Catastrophizing Scale (PCS), State-Trait Anxiety Inventory (STAI), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI-II), Profile of Chronic Pain Scale (PCP:S), Pain Pressure Threshold (PPT), and Conditioned Pain Modulation (CPM). Blood samples were collected to analyze BDNF serum levels. Results At baseline, no significant difference was found regarding all measurements. VAS pain was significantly reduced in the LDN + tDCS (p = 0.010), LDN + tDCS Sham (p= 0.001), and placebo+tDCS Sham (p= 0.009) groups. In the PCP:S, the LDN+tDCS group showed reduced pain frequency and intensity (p= 0.001), effect of pain on activities (p= 0.014) and emotions (p= 0.008). Depressive symptoms reduced after all active interventions (p > 0.001). Conclusion Combined LDN+tDCS has possible benefits in reducing pain frequency and intensity; however, a placebo effect was observed in pain using VAS, and further studies should be performed to analyze the possible association.

Resumo O transporte de peixes vivos é uma prática rotineira na aquicultura e constitui uma fonte considerável de estresse para os animais. A adição de anestésicos na água utilizada para o transporte de peixes pode prevenir ou mitigar os efeitos nocivos do estresse de transporte. Este estudo investigou os efeitos da adição de eugenol (EUG) (1,5 ou 3,0 mL L–1) e óleo essencial de Lippia alba (OEL) (10 ou 20 mL L–1) em parâmetros metabólicos (níveis de glicogênio, lactato e proteína total) no fígado e músculos, a atividade da acetilcolinesterase (AChE) no músculo e no cérebro, e os níveis de proteína carbonil (PC), ácido tiobarbitúrico (TBARS) e grupos tióis não proteicos (NPSH) e atividade da glutationa-S-transferase no fígado de jundiás (Rhamdia quelen; Quoy e Gaimard, 1824) transportados por quatro horas em sacos plásticos (densidade de carga de 169,2 g L–1). A adição de várias concentrações de EUG (1,5 ou 3,0 mL L–1) e OEL (10 ou 20 mL L–1) na água de transporte é aconselhável para o transporte do jundiá, uma vez que ambas concentrações destas substâncias aumentaram os níveis do antioxidante NPSH e diminuíram os níveis de TBARS no fígado. Além disso, os níveis mais baixos de glicogénio e lactato no fígado destes grupos e menor atividade de AChE no cérebro (EOL 10 ou 20 mL L–1) em comparação com o grupo controle indicam que o metabolismo energético e neurotransmissão foram menores após a administração dos anestésicos, contribuindo para a manutenção do estado de homeostase e sedação.

Abstract The transport of live fish is a routine practice in aquaculture and constitutes a considerable source of stress to the animals. The addition of anesthetic to the water used for fish transport can prevent or mitigate the deleterious effects of transport stress. This study investigated the effects of the addition of eugenol (EUG) (1.5 or 3.0 µL L–1) and essential oil of Lippia alba (EOL) (10 or 20 µL L–1) on metabolic parameters (glycogen, lactate and total protein levels) in liver and muscle, acetylcholinesterase activity (AChE) in muscle and brain, and the levels of protein carbonyl (PC), thiobarbituric acid reactive substances (TBARS) and nonprotein thiol groups (NPSH) and activity of glutathione-S-transferase in the liver of silver catfish (Rhamdia quelen; Quoy and Gaimard, 1824) transported for four hours in plastic bags (loading density of 169.2 g L–1). The addition of various concentrations of EUG (1.5 or 3.0 µL L–1) and EOL (10 or 20 µL L–1) to the transport water is advisable for the transportation of silver catfish, since both concentrations of these substances increased the levels of NPSH antioxidant and decreased the TBARS levels in the liver. In addition, the lower liver levels of glycogen and lactate in these groups and lower AChE activity in the brain (EOL 10 or 20 µL L–1) compared to the control group indicate that the energetic metabolism and neurotransmission were lower after administration of anesthetics, contributing to the maintenance of homeostasis and sedation status.

This study evaluated the anesthetic potential of thymol and carvacrol, and their influence on acetylcholinesterase (AChE) activity in the muscle and brain of silver catfish (Rhamdia quelen). The AChE activity of S-(+)-linalool was also evaluated. We subsequently assessed the effects of thymol and S-(+)-linalool on the GABAergic system. Fish were exposed to thymol and carvacrol (25, 50, 75, and 100 mg/L) to evaluate time for anesthesia and recovery. Both compounds induced sedation at 25 mg/L and anesthesia with 50–100 mg/L. However, fish exposed to carvacrol presented strong muscle contractions and mortality. AChE activity was increased in the brain of fish at 50 mg/L carvacrol and 100 mg/L thymol, and decreased in the muscle at 100 mg/L carvacrol. S-(+)-linalool did not alter AChE activity. Anesthesia with thymol was reversed by exposure to picrotoxin (GABAA antagonist), similar to the positive control propofol, but was not reversed by flumazenil (antagonist of benzodiazepine binding site), as observed for the positive control diazepam. Picrotoxin did not reverse the effect of S-(+)-linalool. Thymol exposure at 50 mg/L is more suitable than carvacrol for anesthesia in silver catfish, because this concentration did not cause any mortality or interference with AChE activity. Thymol interacted with GABAA receptors, but not with the GABAA/benzodiazepine site. In contrast, S-(+)-linalool did not act in GABAA receptors in silver catfish.