Mol Pain
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Exosomes are extracellular microvesicles implicated in intercellular communication with ability to transfer cargo molecules, including protein, lipids, and nucleic acids, at both close and distant target sites. It has been shown that exosomes are implicated in physiological and pathological processes. In recent years, the interest on exosomes' role in many pain states has increased. ⋯ Specific molecular patterns characterize exosomes' cargo according to the cellular origin, epigenetic modifications, environmental state, and stressor factors. Therefore, the identification of specific cargo's profile associated to pain states may lead to recognize specific pathological states and to consider the use of exosomes as biomarkers of diseases. Furthermore, exosomes' ability to transfer information and their presence in many accessible biological fluids suggest a potential use as novel non-invasive therapeutic tools in pain field.
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Review
The Etiological Contribution of GABAergic Plasticity to the Pathogenesis of Neuropathic Pain.
Neuropathic pain developing after peripheral or central nerve injury is the result of pathological changes generated through complex mechanisms. Disruption in the homeostasis of excitatory and inhibitory neurons within the central nervous system is a crucial factor in the formation of hyperalgesia or allodynia occurring with neuropathic pain. The central GABAergic pathway has received attention for its extensive distribution and function in neural circuits, including the generation and development of neuropathic pain. ⋯ In this review, we describe possible mechanisms associated with GABAergic plasticity, such as central sensitization and GABAergic interneuron apoptosis, and the epigenetic etiologies of GABAergic plasticity in neuropathic pain. Moreover, we summarize potential therapeutic targets of GABAergic plasticity that may allow for successful relief of hyperalgesia from nerve injury. Finally, we compare the effects of the GABAergic system in neuropathic pain to other types of chronic pain to understand the contribution of GABAergic plasticity to neuropathic pain.
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Fibromyalgia is a disease characterized by chronic widespread pain with additional symptoms, such as joint stiffness, fatigue, sleep disturbance, cognitive dysfunction, and depression. Currently, fibromyalgia diagnosis is based exclusively on a comprehensive clinical assessment, according to 2016 ACR criteria, but validated biological biomarkers associated with fibromyalgia have not yet been identified. Genome-wide association studies investigated genes potentially involved in fibromyalgia pathogenesis highlighting that genetic factors are possibly responsible for up to 50% of the disease susceptibility. ⋯ Furthermore, a gene-environmental interaction has been proposed as triggering mechanism, through epigenetic alterations: In particular, fibromyalgia appears to be characterized by a hypomethylated DNA pattern, in genes implicated in stress response, DNA repair, autonomic system response, and subcortical neuronal abnormalities. Differences in the genome-wide expression profile of microRNAs were found among multiple tissues, indicating the involvement of distinct processes in fibromyalgia pathogenesis. Further studies should be dedicated to strength these preliminary findings, in larger multicenter cohorts, to identify reliable directions for biomarker research and clinical practice.
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Chronic pain is a significant unmet medical problem. Current research regarding sodium channel function in pathological pain is advancing with the hope that it will enable the development of isoform-specific sodium channel blockers, a promising treatment for chronic pain. Before advancements in the pharmacological field, an elucidation of the roles of Nav1.7 and Nav1.8 in the pathophysiology of pain states is required. ⋯ Research concerning the genetic links of Nav1.7 and Nav1.8 in acquired neuropathic and inflammatory pain states from the scientific literature in this field is reported. The role of Nav1.7 and Nav1.8 in the generation and maintenance of abnormal neuronal electrogenesis and hyperexcitability highlights the importance of these channels in the development of pathological pain. However, further research in this area is required to fully elucidate the roles of Nav1.7 and Nav1.8 in the pathophysiology of pain for the development of subtype-specific sodium channel blockers.