Abstract
Neuropathic pain is an intractable chronic pain, caused by damage to the somatosensory nervous system. To date, treatment for neuropathic pain has limited effects. For the development of efficient therapeutic methods, it is essential to fully understand the pathological mechanisms of neuropathic pain. Besides abnormal sensitization in the periphery and spinal cord, accumulating evidence suggests that neural plasticity in the brain is also critical for the development and maintenance of this pain. Recent technological advances in the measurement and manipulation of neuronal activity allow us to understand maladaptive plastic changes in the brain during neuropathic pain more precisely and modulate brain activity to reverse pain states at the preclinical and clinical levels. In this review paper, we discuss the current understanding of pathological neural plasticity in the four pain-related brain areas: the primary somatosensory cortex, the anterior cingulate cortex, the periaqueductal gray, and the basal ganglia. We also discuss potential treatments for neuropathic pain based on the modulation of neural plasticity in these brain areas.
Highlights
Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage [1]
Cheriyan et al reported that cortico-periaqueductal gray (PAG) neurons showed a significant reduction in intrinsic excitability in brain slices of mice with neuropathic pain induced by constrictive injury (CCI) [84]
Recent development of technological tools, such as optogenetics, chemogenetics, and brain imaging, in rodent models allows us to understand the relationship between the regulation of neurotransmitters in the brain and chronic pain conditions [113]
Summary
Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage [1]. Analgesic drugs currently being applied in clinical practice for neuropathic pain have serious adverse effects, such as depression, memory loss, nystagmus, and addiction [9,10]. Neural plasticity in the brain has been reported to be involved in the development and maintenance of neuropathic pain [12]. Neuropathic pain is accompanied by systemic plastic changes in the brain This neural plasticity ranges from functional to structural changes in neurons. Biomedicines 2021, 9, 624 reversal of neural plasticity leads to analgesic effects, indicating that this modulation can be a potential therapeutic method for neuropathic pain. Cortical areas such as the primary somatosensory cortex (S1) and the anterior cingulate cortex (ACC) have been frequently reported to be associated with neuropathic pain [14,17]. We discuss neural plasticity in the above four areas of the brain during neuropathic pain and potential treatments based on the modulation of neural plasticity in each brain area
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