The endocannabinoid system (eCB) has been studied to identify the molecular structures present in Cannabis sativa. eCB consists of cannabinoid receptors, endogenous ligands, and the associated enzymatic apparatus responsible for maintaining energy homeostasis and cognitive processes. Several physiological effects of cannabinoids are exerted through interactions with various receptors, such as CB1 and CB2 receptors, vanilloid receptors, and the recently discovered G-protein-coupled receptors (GPR55, GPR3, GPR6, GPR12, and GPR19). Anandamide (AEA) and 2-arachidoylglycerol (2-AG), two small lipids derived from arachidonic acid, showed high-affinity binding to both CB1 and CB2 receptors. eCB plays a critical role in chronic pain and mood disorders and has been extensively studied because of its wide therapeutic potential and because it is a promising target for the development of new drugs. Phytocannabinoids and synthetic cannabinoids have shown varied affinities for eCB and are relevant to the treatment of several neurological diseases. This review provides a description of eCB components and discusses how phytocannabinoids and other exogenous compounds may regulate the eCB balance. Furthermore, we show the hypo- or hyperfunctionality of eCB in the body and how eCB is related to chronic pain and mood disorders, even with integrative and complementary health practices (ICHP) harmonizing the eCB.

5′-4-Alkyl/aryl-1H-1,2,3-triazole derivatives PILAB 1–12 were synthesized and a pharmacological screening of these derivatives was performed to identify a possible effect on the Central Nervous System (CNS) and to explore the associated mechanisms of action. The mice received a peritoneal injection (100 µmol/kg) of each of the 12 PILAB derivatives 10 min prior to the injection of pentobarbital and the mean hypnosis times were recorded. The mean hypnosis time increased for the mice treated with PILAB 8, which was prevented when mice were administered CTOP, a µ-opioid antagonist. Locomotor and motor activities were not affected by PILAB 8. The anxiolytic effect of PILAB 8 was evaluated next in an elevated-plus maze apparatus. PILAB 8 and midazolam increased a percentage of entries and spent time in the open arms of the apparatus compared with the control group. Conversely, a decrease in the percentages of entries and time spent in the closed arms were observed. Pretreatment with naloxone, a non-specific opioid antagonist, prior to administration of PILAB 8 exhibited a reverted anxiolytic effect. PILAB 8 exhibited antinociceptive activity in the hot plate test, and reduced reactivity to formalin in the neurogenic and the inflammatory phases. These data suggest that PILAB 8 can activate µ-opioid receptors to provoke antinociceptive and anti-inflammatory effects in mice.

Cannabigerol (CBG), a phytocannabinoid, has shown promise in pain management. Previous studies by our research group identified an increase in pain sensitivity as a consequence of prenatal hypoxia-ischemia (HI) in an animal model. This study aimed to investigate the efficacy of CBG in acute and chronic hyperalgesia induced by prenatal HI. A pharmacological screening was first conducted using hot plate and open-field tests to evaluate the antinociceptive and locomotor activities of animals administered with a 50 mg/kg oral dose of cannabis extract with a high CBG content. Prenatal HI was induced in pregnant rats, and the offspring were used to evaluate the acute antinociceptive effect of CBG in the formalin-induced peripheral pain model, while chronic antinociceptive effects were observed through spinal nerve ligation (SNL) surgery, a model used to induce neuropathic pain. Our results show that CBG exhibited an antinociceptive effect in the hot plate test without affecting the animals’ motor function in the open-field test. CBG significantly reduced formalin-induced reactivity in HI offspring during both the neurogenic and inflammatory phases. CBG treatment alleviated thermal and mechanical hypernociception induced by SNL. Biomolecular analysis revealed CBG’s ability to modulate expression, particularly reducing TNFα and Nav1.7 in HI male and female rats, respectively. These results highlight CBG as a potential antinociceptive agent in acute and chronic pain models, suggesting it as a promising therapeutic option without inducing motor impairment. Further research is needed to fully elucidate its mechanisms and clinical applications in pain management.

The number of publications on the development of arthritic pain after CHIKV infection is increasing; however, there is still a gap in the pathophysiological mechanisms that explain these outcomes. In this review, we conducted a descriptive analysis of the findings of patients to understand their prognosis and to explore therapeutic options. Here, we searched the Cochrane, BVS, PubMed, and Scielo databases using the keywords “arthritis”, “pain”, “arbovirus”, “disease”, “arthritogenic”, and “arthralgia” during the 2000 to 2022 period. Descriptive analyses were conducted to understand the association between CHIKV infection and arthritogenic pain. The present study shows the persistence of acute phase signals for months, making the chronic phase still marked by the presence of arthralgia, often disabling under stimuli, such as temperature variation. CHIKV infection appears to be remarkably similar to rheumatoid arthritis, since both diseases share common symptoms. Once diagnosed, patients are mostly treated with analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease modifying anti-rheumatic drugs (DMARD). As there are no prophylactic measures or specific treatments for arboviruses, this study gathered information on the development and manifestations of arthritogenic pain.

Brazil is a country with the greatest biodiversity in the world, but much of it is still largely unexplored. Trigynaea axilliflora (Annonaceae) is a Brazilian plant species that has not been previously studied. This research aimed to characterize the chemical constituents and evaluate the biological activities of the extract, fractions and isolated compounds. Xylopine, a major compound isolated from this extract, is an aporphine alkaloid and a chemotaxonomic marker of this family, whose structure was confirmed by ¹H/¹³C NMR and HRESIMS. HPLC-UV-ESI-qTOF dereplication indicated that xylopine and seven other aporphine alkaloids were present in the crude extract. A solvent washing procedure allowed the recovery of 138 mg of xylopine, with a yield of 13.8% (138 mg/g crude extract) and 95% purity by HPLC-DAD. Cytotoxicity by the MTT assay showed that xylopine was active against MG-63 osteosarcoma cells (IC₅₀ = 5.5 μg/mL), with a selectivity index (SI = 0.63) indicating a favorable selectivity compared to doxorubicin (SI = 0.22). Antibacterial assays demonstrated the inhibition of Staphylococcus aureus and Escherichia coli by the ethanolic extract and chloroform fraction (MIC 125–500 μg/mL), as well as by xylopine (MIC 62.5 μg/mL for S. aureus and 31.2 μg/mL for E. coli). To evaluate antinociceptive activity, the formalin test was used, and both the ethanolic extract and xylopine significantly reduced nociceptive behavior during the inflammatory phase from 123.8 ± 13.7 s (100%) to 71.3 ± 10.2 s (57.5%) and 1.3 ± 0.4 s (1%), respectively, at doses of 30 mg/kg. In silico pharmacokinetic analysis using SwissADME predicted favorable drug-likeness and oral bioavailability for xylopine, supporting its potential as a drug candidate. This study presents the first report on the chemical profile and bioactivities of T. axilliflora, suggesting it as a possible natural source of xylopine. This finding highlights the importance of phytochemical and pharmacological research in understanding Brazil’s understudied flora.