Efficacy and Security of Tetrodotoxin in the Treatment of Cancer-Related Pain: Systematic Review and Meta-Analysis.

The pharmacological treatment of cancer-related pain is unsatisfactory. Tetrodotoxin (TTX) has shown analgesia in preclinical models and clinical trials, but its clinical efficacy and safety have not been quantified. For this reason, our aim was to perform a systematic review and meta-analysis of the clinical evidence that was available. A systematic literature search was conducted in four electronic databases (Medline, Web of Science, Scopus, and ClinicalTrials.gov) up to 1 March 2023 in order to identify published clinical studies evaluating the efficacy and security of TTX in patients with cancer-related pain, including chemotherapy-induced neuropathic pain. Five articles were selected, three of which were randomized controlled trials (RCTs). The number of responders to the primary outcome (≥30% improvement in the mean pain intensity) and those suffering adverse events in the intervention and placebo groups were used to calculate effect sizes using the log odds ratio. The meta-analysis showed that TTX significantly increased the number of responders (mean = 0.68; 95% CI: 0.19-1.16, p = 0.0065) and the number of patients suffering non-severe adverse events (mean = 1.13; 95% CI: 0.31-1.95, p = 0.0068). However, TTX did not increase the risk of suffering serious adverse events (mean = 0.75; 95% CI: -0.43-1.93, p = 0.2154). In conclusion, TTX showed robust analgesic efficacy but also increased the risk of suffering non-severe adverse events. These results should be confirmed in further clinical trials with higher numbers of patients.

The experience of vertigo: A systematic review of neuroimaging studies.

Our primary objective was to assess consistent activation and deactivation among healthy participants and patients reporting vertigo. Our secondary aim was to evaluate the influence of the stimulus and the direction of the perception of self-motion We realized a systematic review with an extensive data visualization. We included neuroimaging studies (e.g., functional magnetic resonance imaging [fMRI], positron emission tomography [PET] or near infrared spectroscopy [NIRS]) that have measured functional activity in human adults reporting vertigo and/or dizziness. We included 21 studies (n = 336 participants), ~ 64% male, age ranging from 18 to 80.5 years. The different stimuli used to induce vertigo: caloric stimulation, galvanic stimulation, visual stimulation or vibratory stimulus on neck muscles. We found a consistent activation of the insular cortex, inferior parietal lobule, putamen, cerebellum, anterior cingulate cortex, precentral gyrus, superior temporal gyrus and thalamus. Cortical and subcortical activation seems to have a contralateral pattern to the perception of self-movement. We found a deactivation pattern of structures related to the ventral and third visual pathway. Vertigo is an unpleasant and subjective experience which involves multiple vestibular and non-specific networks with the involvement of a cortico-basal ganglia- cerebellar-thalamic network.