Abstract
Chronic neuropathic pain, a type of chronic and potentially disabling pain caused by a disease or injury of the somatosensory nervous system, spinal cord injury, or various chronic conditions, such as viral infections (e.g., post-herpetic neuralgia), autoimmune diseases, cancers, and metabolic disorders (e.g., diabetes mellitus), is one of the most intense types of chronic pain, which incurs a major socio-economic burden and is a serious public health issue, with an estimated prevalence of 7–10% in adults throughout the world. Presently, the available drug treatments (e.g., anticonvulsants acting at calcium channels, serotonin-noradrenaline reuptake inhibitors, tricyclic antidepressants, opioids, topical lidocaine, etc.) for chronic neuropathic pain patients are still rare and have disappointing efficacy, which makes it difficult to relieve the patients’ painful symptoms, and, at best, they only try to reduce the patients’ ability to tolerate pain. Long non-coding RNAs (lncRNAs), a type of transcript of more than 200 nucleotides with no protein-coding or limited capacity, were identified to be abnormally expressed in the spinal cord, dorsal root ganglion, hippocampus, and prefrontal cortex under chronic neuropathic pain conditions. Moreover, a rapidly growing body of data has clearly pointed out that nearly 40% of lncRNAs exist specifically in the nervous system. Hence, it was speculated that these dysregulated lncRNAs might participate in the occurrence, development, and progression of chronic neuropathic pain. In other words, if we deeply delve into the potential roles of lncRNAs in the pathogenesis of chronic neuropathic pain, this may open up new strategies and directions for the development of novel targeted drugs to cure this refractory disorder. In this article, we primarily review the status of chronic neuropathic pain and provide a general overview of lncRNAs, the detailed roles of lncRNAs in the nervous system and its related diseases, and the abnormal expression of lncRNAs and their potential clinical applications in chronic neuropathic pain. We hope that through the above description, readers can gain a better understanding of the emerging roles of lncRNAs in chronic neuropathic pain.
Highlights
Most extensive evidence has definitely pointed out that there were many dysregulated Long non-coding RNAs (lncRNAs) expressed in damaged nerves, primary sensory dorsal root ganglion neurons, spinal cord dorsal roots, the prefrontal cortex, the post-synaptic dorsal horn, and even in higherorder neurons up to the cortical level after peripheral nerve injury; it was speculated that these dysregulated lncRNAs might be involved in the pathogenesis of chronic neuropathic pain (Li et al, 2019)
Chronic neuropathic pain patients are often characterized by symptoms of spasticity, muscle weakness, dysesthesia, spontaneous pain, allodynia, hyperalgesia, poor proprioception, and so on (Gilron et al, 2015)
Previous studies have precisely revealed that the available analgesics, such as non-steroidal anti-inflammatory drugs and opioids, which could effectively improve the clinical signs or symptoms of nociceptive pain, did not produce an adequate effect on chronic neuropathic pain patients (Vranken, 2012)
Summary
Chronic Neuropathic PainAn epidemiological survey has clearly revealed that nearly 19% of adult Europeans suffered from chronic pain of moderate to severe intensity, which seriously affected the physical and mental quality of their social and working lives and represents a significant public health issue that can be costly to the healthcare system (Rapo-Pylkko et al, 2017). DGCR5 overexpression was able to alleviate neuropathic pain development including mechanical and thermal hyperalgesia through sponging miR-330-3p and regulating PDCD4 in CCI rat models.
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