Pain is an unpleasant sensory and emotional experience associated with,or resembling that associated with,actual or potential tissue damage.The processing of pain involves complicated modulation at the levels of the p...Pain is an unpleasant sensory and emotional experience associated with,or resembling that associated with,actual or potential tissue damage.The processing of pain involves complicated modulation at the levels of the periphery,spinal cord,and brain.The pathogenesis of chronic pain is still not fully understood,which makes the clinical treatment challenging.Optogenetics,which combines optical and genetic technologies,can precisely intervene in the activity of specific groups of neurons and elements of the related circuits.Taking advantage of optogenetics,researchers have achieved a body of new findings that shed light on the cellular and circuit mechanisms of pain transmission,pain modulation,and chronic pain both in the periphery and the central nervous system.In this review,we summarize recent findings in pain research using optogenetic approaches and discuss their significance in understanding the pathogenesis of chronic pain.展开更多
Spinal cord injury (SCI) currently ranks second after mental retarda- tion among neurological disorders in terms of cost to society. Pain is a debilitating consequence of SCI related to the nature of the lesion, neu...Spinal cord injury (SCI) currently ranks second after mental retarda- tion among neurological disorders in terms of cost to society. Pain is a debilitating consequence of SCI related to the nature of the lesion, neurological structures damaged, and secondary pathophysiological changes of surviving tissues (Yezierski, 2005; D'Angelo et al., 2013).展开更多
Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs (...Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs (NSAIDs), or opiates. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic (intraperitoneal) administration of NSAIDs induces antinociception with some effects of tolerance. In this review, we report that repeated microinjection of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, the periaqueductal grey-rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system. These data are important for human medicine. In particular, cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.展开更多
Protein kinase D (PKD) is an evolutionarily-conserved family of protein kinases. It has structural, regulatory, and enzymatic properties quite different from the PKC family. Many stimuli induce PKD signaling, includ...Protein kinase D (PKD) is an evolutionarily-conserved family of protein kinases. It has structural, regulatory, and enzymatic properties quite different from the PKC family. Many stimuli induce PKD signaling, including G-protein-coupled receptor agonists and growth factors. PKD1 is the most studied member of the family. It functions during cell proliferation, differentiation, secretion, cardiac hypertrophy, immune regulation, angiogenesis, and cancer. Previously, we found that PKD1 is also critically involved in pain modulation. Since then, a series of studies performed in our lab and by other groups have shown that PKDs also participate in other processes in the nervous system including neuronal polarity establishment, neuroprotection, and learning. Here, we discuss the connections between PKD structure, enzyme function, and localization, and summarize the recent findings on the roles of PKD-mediated signaling in the nervous system.展开更多
基金supported by grants from the National Natural Science Foundation of China(82073819 and 81872843)Fundamental Research Funds for the Central Universities of China(2021QNA7005).
文摘Pain is an unpleasant sensory and emotional experience associated with,or resembling that associated with,actual or potential tissue damage.The processing of pain involves complicated modulation at the levels of the periphery,spinal cord,and brain.The pathogenesis of chronic pain is still not fully understood,which makes the clinical treatment challenging.Optogenetics,which combines optical and genetic technologies,can precisely intervene in the activity of specific groups of neurons and elements of the related circuits.Taking advantage of optogenetics,researchers have achieved a body of new findings that shed light on the cellular and circuit mechanisms of pain transmission,pain modulation,and chronic pain both in the periphery and the central nervous system.In this review,we summarize recent findings in pain research using optogenetic approaches and discuss their significance in understanding the pathogenesis of chronic pain.
文摘Spinal cord injury (SCI) currently ranks second after mental retarda- tion among neurological disorders in terms of cost to society. Pain is a debilitating consequence of SCI related to the nature of the lesion, neurological structures damaged, and secondary pathophysiological changes of surviving tissues (Yezierski, 2005; D'Angelo et al., 2013).
基金supported by the grant from Georgian National Science Foundation,No.GNSF/ST07/6-234
文摘Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs (NSAIDs), or opiates. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic (intraperitoneal) administration of NSAIDs induces antinociception with some effects of tolerance. In this review, we report that repeated microinjection of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, the periaqueductal grey-rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system. These data are important for human medicine. In particular, cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.
基金supported by the National Natural Science Foundation of China (81161120497, 30925015, 30830044, 30900582, and 81221002)the National Basic Research Development Program (973 Program) of China (2014CB542204)
文摘Protein kinase D (PKD) is an evolutionarily-conserved family of protein kinases. It has structural, regulatory, and enzymatic properties quite different from the PKC family. Many stimuli induce PKD signaling, including G-protein-coupled receptor agonists and growth factors. PKD1 is the most studied member of the family. It functions during cell proliferation, differentiation, secretion, cardiac hypertrophy, immune regulation, angiogenesis, and cancer. Previously, we found that PKD1 is also critically involved in pain modulation. Since then, a series of studies performed in our lab and by other groups have shown that PKDs also participate in other processes in the nervous system including neuronal polarity establishment, neuroprotection, and learning. Here, we discuss the connections between PKD structure, enzyme function, and localization, and summarize the recent findings on the roles of PKD-mediated signaling in the nervous system.