Current Neuropharmacology - Volume 19, Issue 3, 2021

Background: Primary and metastatic bone tumor incidence has increased in the previous years. Pain is a common symptom and is one of the most important related factors to the decrease of quality of life in patients with bone tumor. Different pain management strategies are not completely effective and many patients afflicted by cancer pain cannot be controlled properly. In this sense, we need to elucidate the neurophysiology of cancer-induced pain, contemplating other components such as inflammation, neuropathies and cognitive components regarding bone tumors, and thus pave the way for novel therapeutic approaches in this field. Aim: This study aims to identify the neurophysiology of the mechanisms related to pain management in bone tumors. Methods: Advanced searches were performed in scientific databases: PubMed, ProQuest, EBSCO, and the Science Citation index to get information about the neurophysiology mechanisms related to pain management in bone tumors. Results: The central and peripheral mechanisms that promote bone cancer pain are poorly understood. Studies have shown that bone cancer could be related to neurochemicals produced by tumor and inflammatory cells, coupled with peripheral sensitization due to nerve compression and injury caused by tumor growth. The activity of mesolimbic dopaminergic neurons, substance P, cysteine/ glutamate antiporter, and other neurochemical dynamics brings us putative strategies to suggest better and efficient treatments against pain in cancer patients. Conclusion: Cancer-induced bone pain could include neuropathic and inflammatory pain, but with different modifications to the periphery tissue, nerves and neurochemical changes in different neurological levels. In this sense, we explore opportunity areas in pharmacological and nonpharmacological pain management, according to pain-involved mechanisms in this study.

Background: Trigeminal neuralgia is a chronic disease characterized by intense facial pain that is caused by trigeminal nerve affectation. It usually affects adults from 50 years of age, and is more frequent in women. Additionally, it presents serious psychological effects that often lead to depression, which is why it is considered highly disabling. The therapeutic approach is based on the modification of nerve activity through electrical, surgical or chemical stimulation in specific regions of the nervous system. Objective: To perform a meta-analysis of the scientific literature related to invasive and non-invasive electrical neuromodulation of trigeminal neuralgia, in order to assess their effects over pain and adverse effects. Methods: A literature search was conducted in 4 databases, followed by a manual search of articles on invasive or non-invasive electrical neuromodulation to control the pain of trigeminal neuralgia, including the last 15 years. Results: Regarding non-invasive methods, clinical trials did not present enough results in order to perform a meta-analysis. Regarding invasive methods, clinical trials meta-analysis showed no statistical differences between different treatment methods. In all cases, improvements in patients' pain were reported, although results regarding adverse effects were variable. Conclusion: In the treatment of trigeminal neuralgia, the continuous radiofrequency provides better short and medium-term results, but pulsed radiofrequency shows less adverse effects after treatment, and has better results in the long-term.

Background: For more than seven decades, ultrasound has been used as an imaging and diagnostic tool. Today, new technologies, such as focused ultrasound (FUS) neuromodulation, have revealed some innovative, potential applications. However, those applications have been barely studied to deal with neuropathic pain (NP), a cluster of chronic pain syndromes with a restricted response to conventional pharmaceuticals. Objective: To analyze the therapeutic potential of low-intensity (LIFUS) and high-intensity (HIFUS) FUS for managing NP. Methods: We performed a narrative review, including clinical and experimental ultrasound neuromodulation studies published in three main database repositories. Discussion: Evidence shows that FUS may influence several mechanisms relevant for neuropathic pain management such as modulation of ion channels, glutamatergic neurotransmission, cerebral blood flow, inflammation and neurotoxicity, neuronal morphology and survival, nerve regeneration, and remyelination. Some experimental models have shown that LIFUS may reduce allodynia after peripheral nerve damage. At the same time, a few clinical studies support its beneficial effect on reducing pain in nerve compression syndromes. In turn, Thalamic HIFUS ablation can reduce NP from several etiologies with minor side-effects, but some neurological sequelae might be permanent. HIFUS is also useful in lowering non-neuropathic pain in several disorders. Conclusion: Although an emerging set of studies brings new evidence on the therapeutic potential of both LIFUS and HIFUS for managing NP with minor side-effects, we need more controlled clinical trials to conclude about its safety and efficacy.

Neurological disorders and their sequelae, as of the widespread and critical humans’ complications, affect the body's nervous systems, organ functions, and behaviors. According to WHO, neurological disorders are currently predicted to affect more than one billion people globally. It is well-established that complementary medicine is one of the high accepted interventions that could have been considered for the management of neurological ailments. The current review aimed to compile all the crucial data reporting the investigation on the conspicuous intervention of green tea (made of Camellia sinensis) and related lead compounds (especially l-theanine, epigallocatechin- 3-gallate, epicatechin-3-gallate, epicatechin, and epigallocatechin) for their neurological activities, mechanisms of action, and clinical properties. According to the documents, green tea exhibits antidepressant, anti-neurodegenerative (e.g., anti-Parkinson and anti-Alzheimer), as well as neuroprotective effects.Chief among them, for offering novel work, it is worth focusing on several related assessments with great attention to more extensive standardized clinical trials, and subsequently more in-depth pharmacokinetic studies to safely introduce this beneficial medicinal food as a neuro-effective agent.

Borderline Personality Disorder (BPD) is a chronic debilitating psychiatric disorder characterized mainly by emotional instability, chaotic interpersonal relationships, cognitive disturbance (e.g., dissociation and suicidal thoughts) and maladaptive behaviors. BPD has a high rate of comorbidity with other mental disorders and a high burden on society. In this review, we focused on two compromised brain regions in BPD - the hypothalamus and the corticolimbic system, emphasizing the involvement and potential contribution of the endocannabinoid system (ECS) to improvement in symptoms and coping. The hypothalamus-regulated endocrine axes (hypothalamic pituitary – gonadal, thyroid & adrenal) have been found to be dysregulated in BPD. There is also substantial evidence for limbic system structural and functional changes in BPD, especially in the amygdala and hippocampus, including cortical regions within the corticolimbic system. Extensive expression of CB1 and CB2 receptors of the ECS has been found in limbic regions and the hypothalamus. This opens new windows of opportunity for treatment with cannabinoids such as cannabidiol (CBD) as no other pharmacological treatment has shown long-lasting improvement in the BPD population to date. This review aims to show the potential role of the ECS in BPD patients through their most affected brain regions, the hypothalamus and the corticolimbic system. The literature reviewed does not allow for general indications of treatment with CBD in BPD. However, there is enough knowledge to indicate a treatment ratio of a high level of CBD to a low level of THC. A randomized controlled trial investigating the efficacy of cannabinoid based treatments in BPD is warranted.

Restless legs syndrome (RLS)/Willis-Ekbom disease is a neurologic disorder characterized by a strong desire to move when at rest (usually in the evening) and paraesthesia in their lower legs. The most widely used therapies for first-line treatment of RLS are dopaminergic drugs; however, their long-term use can lead to augmentation. α2δ Ligands, opioids, iron, glutamatergic drugs, adenosine, and sleep aids have been investigated as alternatives. The pathogenesis of RLS is not well understood. Despite the efficacy of dopaminergic drugs in the treatment of this disorder, unlike in Parkinson’s disease dopaminergic cell loss in the substantia nigra has not been observed in RLS. The etiology of RLS is likely complex, involving multiple neural pathways. RLS-related genes identified in genome-wide association studies can provide insight into the mechanistic basis and pathophysiology of RLS. Here we review the current treatments and knowledge of the mechanisms underlying RLS.

Retinoic acid, a metabolite of vitamin A, acts through either genomic or nongenomic actions. The genomic action of retinoids exerts effects on gene transcription through interaction with retinoid receptors such as retinoic acid receptors (RARα, β, and γ) and retinoid X receptors (RXRα, β, and γ) that are primarily concentrated in the amygdala, pre-frontal cortex, and hippocampal areas in the brain. In response to retinoid binding, RAR/RXR heterodimers undergo major conformational changes and orchestrate the transcription of specific gene networks. Previous experimental studies have reported that retinoic acid exerts an antiepileptogenic effect through diverse mechanisms, including the modulation of gap junctions, neurotransmitters, long-term potentiation, calcium channels and some genes. To our knowledge, there are no previous or current clinical trials evaluating the use of retinoic acid for seizure control.

Introduction: Some medicinal plants have shown promising therapeutic potential for the management of the diseases. We aimed to systematically review the literature wherein the therapeutic effects of saffron have been studied on eye disorders. Methods: A systematic literature search was performed in PubMed, Scopus, Web of Science, Google scholar and other databases using eye disorders and saffron as key terms. No strict inclusion criteria were defined, and almost all clinical studies, as well as in vivo and in vitro studies were included. The reported data in each study were extracted and then qualitatively described. Results: Finally, 78 articles were found but only 29 relevant articles were included. Nine articles were clinical trials and 20 articles were studies conducted on cellular and molecular aspects of saffron on eye disorders. According to the included studies, crocin prevented the pro-inflammatory response in retinal cells and decreased glucose levels in diabetic mice. Also, crocetin prevented retinal degeneration and saffron protected photoreceptors from light-induced damage in retinal cells. Saffron also improved visual function in age-related macular edema and decreased intraocular pressure in patients with glaucoma. In addition, it was shown that crocin can improve best corrected visual acuity and decrease central macular thickness in patients with diabetic maculopathy. Conclusion: The results of this review indicated that saffron and its main ingredients such as crocin could be a potential candidate for the treatment of ocular disease especially eye inflammation; however, further clinical studies are needed to confirm such efficiency.

Background: People with spinal cord injuries (SCI) commonly experience pain and spasticity; limitations of current treatments have generated interest in cannabis as a possible therapy. Objectives: We conducted this systematic review to: 1) examine usage patterns and reasons for cannabinoid use, and 2) determine the treatment efficacy and safety of cannabinoid use in people with SCI. Methods: PubMed, Embase, Web of Science and Cumulative Index to Nursing and Allied Health Literature databases were queried for keywords related to SCI and cannabinoids. Results: 7,232 studies were screened, and 34 were included in this systematic review. Though 26 studies addressed cannabinoid usage, only 8 investigated its therapeutic potential on outcomes such as pain and spasticity. The most common method of use was smoking. Relief of pain, spasticity and recreation were the most common reasons for use. A statistically significant reduction of pain and spasticity was observed with cannabinoid use in 83% and 100% of experimental studies, respectively. However, on examination of randomized control trials (RCTs) alone, effect sizes ranged from - 0.82 to 0.83 for pain and -0.95 to 0.09 for spasticity. Cannabinoid use was associated with fatigue and cognitive deficits. Conclusion: Current evidence suggests that cannabinoids may reduce pain and spasticity in people with SCI, but its effect magnitude and clinical significance are unclear. Existing information is lacking on optimal dosage, method of use, composition and concentration of compounds. Long-term, double-blind, RCTs, assessing a wider range of outcomes should be conducted to further understand the effects of cannabinoid use in people with SCI.