Neuropathic pain is characterized by abnormal hypersensitivity to stimuli (hyperalgesia) and nociceptive responses to non-noxious stimuli (allodynia). The conditions and the pathophysiological states that determine the onset of neuropathic pain are heterogeneous, such as metabolic disorders, neuropathy caused by viral infections, and autoimmune diseases affecting the central nervous system (CNS). Neuropathic pain in the general population is estimated to have a prevalence ranging between 3% and 17%. Most of the available treatments for neuropathic pain have moderate efficacy and present side effects that limit their use; therefore, other therapeutic approaches are needed for patients. In this article, the current standard of care treatment, the emerging pharmacological approaches from the completed phase III clinical trials, and the preclinical studies on novel promising therapeutic options will be reviewed.

Cannabidiol (CBD) is one of the cannabinoids with non-psychotropic action, extracted from Cannabis sativa. CBD is a terpenophenol and it has received a great scientific interest thanks to its medical applications. This compound showed efficacy as anti-seizure, antipsychotic, neuroprotective, antidepressant and anxiolytic. The neuroprotective activity appears linked to its excellent anti-inflammatory and antioxidant properties. The purpose of this paper is to evaluate the use of CBD, in addition to common anti-epileptic drugs, in the severe treatment-resistant epilepsy through an overview of recent literature and clinical trials aimed to study the effects of the CBD treatment in different forms of epilepsy. The results of scientific studies obtained so far the use of CBD in clinical applications could represent hope for patients who are resistant to all conventional anti-epileptic drugs.

In physiological conditions, different types of macrophages can be found within the central nervous system (CNS), i.e., microglia, meningeal macrophages, and perivascular (blood-brain barrier) and choroid plexus (blood-cerebrospinal fluid barrier) macrophages. Microglia and tissue-resident macrophages, as well as blood-borne monocytes, have different origins, as the former derive from yolk sac erythromyeloid precursors and the latter from the fetal liver or bone marrow. Accordingly, specific phenotypic patterns characterize each population. These cells function to maintain homeostasis and are directly involved in the development and resolution of neuroinflammatory processes. Also, following inflammation, circulating monocytes can be recruited and enter the CNS, therefore contributing to brain pathology. These cell populations have now been identified as key players in CNS pathology, including autoimmune diseases, such as multiple sclerosis, and degenerative diseases, such as Amyotrophic Lateral Sclerosis and Alzheimer’s disease. Here, we review the evidence on the involvement of CNS macrophages in neuroinflammation and the advantages, pitfalls, and translational opportunities of pharmacological interventions targeting these heterogeneous cellular populations for the treatment of brain diseases.

Macrophage Migration Inhibitory Factor (MIF) is a pro-inflammatory cytokine expressed by a variety of cell types. Although MIF has been primarily studied for its role in the pathogenesis of autoimmune diseases, it has also been shown to promote tumorigenesis and it is over expressed in various malignant tumors. MIF is able to induce angiogenesis, cell cycle progression, and to block apoptosis. As tailored therapeutic approaches for the inhibition of endogenous MIF are being developed, it is important to evaluate the role of MIF in individual neoplastic conditions that may benefit from specific MIF inhibitors. Along with this line, in this paper, we have reviewed the evidence of the involvement of MIF in the etiopathogenesis and progression of glioblastoma and the preclinical data suggesting the possible use of specific MIF inhibition as a potential novel therapeutic strategy for brain tumors.