Schizophrenia (SZ) is a complex psychiatric disorder characterized by disruptions in cognition, perception, and behavior, contributing significantly to the global burden of psychiatric disorders and necessitating ongoing research into its pathophysiology, diagnosis, and treatment. This narrative review explores recent insights into SZ research, highlighting the genetic, neurochemical, and neurodevelopmental factors that contribute to the disorder. Emerging evidence underscores the dynamic interplay between neurotransmitter imbalances, particularly involving dopamine, glutamate, and gamma-aminobutyric acid (GABA), and neuroinflammation, oxidative stress, and immune dysregulation in the pathophysiology of SZ. Neuroimaging, clinical staging models, and multi-omics technologies have deepened our understanding of structural and functional brain abnormalities, identifying potential biomarkers for early detection and subtyping. This has refined diagnostic frameworks and informed precision psychiatry approaches. Advances in pharmacological treatments, including trace amine-associated receptor 1 agonists, glutamatergic modulators, psychedelics, and anti-inflammatory agents, offer new therapeutic possibilities beyond conventional dopamine antagonists. Novel targets, such as N-methyl-D-aspartate (NMDA) receptor modulation and neuroprotective strategies, are also being explored to address negative and cognitive symptoms. Additionally, non-pharmacological interventions, such as neuromodulation techniques, digital therapeutics, and psychosocial interventions, are promising complementary strategies. Digital phenotyping, machine learning (ML), and artificial intelligence (AI)-driven tools enable real-time symptom tracking, early risk prediction, and personalized care delivery. Despite these advancements, challenges remain in early diagnosis, treatment adherence, and equitable access to mental health care, particularly in low-resource settings. Therefore, addressing these barriers requires interdisciplinary collaboration, public health education, and the integration of scalable, culturally sensitive, and AI-based mental health innovations. Future research should prioritize multi-omics integration, longitudinal and transdiagnostic studies, biomarker validation, and the real-world implementation of personalized interventions to improve outcomes and quality of life for individuals living with SZ.

Neuropathic pain, defined by the International Association for the Study of Pain as “pain caused by a lesion or disease of the somatosensory system”, has an estimated prevalence of 7–9.2% in the general population and is associated with poorer health-related quality of life than other types of pain. Diagnosis can be improved by the use of diagnostic algorithms, but treatment remains rather unsatisfactory, with only 30–40% of patients achieving an acceptable response. Some authors have suggested that the poor results in the treatment of neuropathic pain may be related to the different mechanisms present in each patient and have tried to correlate them with clinical characteristics in order to evaluate possible targeted treatments. This approach has been used in some studies evaluating the response to specific pharmacotherapies in clusters of patients, with encouraging results but still limited applicability to clinical practice. In this narrative review, we attempt to analyse the literature suggesting possible pathogenetic mechanisms manifested along the nociceptive pathway due to a lesion or disease of the nervous system; aware of the limitations of exploring such a wide field, we look for conditions that could be targeted by the available pharmacological or interventional treatment options. Functional changes may occur in the nociceptive system from the periphery to the cerebral cortex, in particular in the nociceptive terminals, along the first-order neuron and the dorsal root ganglion, at the first synapses, or at supraspinal levels. Clinical assessment is the first step in the study of anatomical and functional changes; the diagnostic hypothesis should be confirmed, if possible, by instrumental studies or diagnostic blocks or procedures to guide an individualised therapeutic algorithm from less to more invasive treatments.

Purinergic signaling, mediated by ATP and adenosine receptors, plays a crucial role in cellular communication and homeostasis within the central nervous system (CNS), particularly by regulating synaptic activity, glial cell functions, and neuroplasticity. Glial cells, including astrocytes and microglia, contribute to both short-term processes, such as neurotransmission and neuroinflammation, and long-term functions, including synaptic remodeling, tissue repair, and behavioral adaptation. Dysregulation of purinergic signaling in these cells has been implicated in the pathogenesis of various neurodegenerative and neuropsychiatric disorders. This article explores the evolving concept of the synapse, highlighting the active role of glial cells in synaptic modulation and emphasizing the significance of purinergic signaling in synaptic function and responses to conditions such as injury and neurotoxicity. Specifically, it examines the roles of ATP and adenosine receptors—such as P2X4, P2X7, P2Y1, and P2Y12—in mediating key astrocytic and microglial functions, including neuroinflammation, phagocytosis, synaptic plasticity, and neuronal damage. Furthermore, the article discusses the involvement of purinergic receptors in neurological disorders such as epilepsy, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, ischemic stroke, Rett syndrome, and autism spectrum disorder, as well as potential therapeutic strategies targeting these receptors to mitigate inflammation, promote tissue repair, and improve clinical outcomes.