Articles: cations.
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Acute and chronic itch are prevalent and incapacitating, yet the neural mechanisms underlying both acute and chronic itch are just starting to be unraveled. Activated transcription factor 4 (ATF4) belongs to the ATF/CREB transcription factor family and primarily participates in the regulation of gene transcription. Our previous study has demonstrated that ATF4 is expressed in sensory neurons. ⋯ Furthermore, ATF4 interacts with the transient receptor potential cation channel subfamily V member 4 (TRPV4) and inhibits its function without altering the expression or membrane trafficking of TRPV4 in sensory neurons. In addition, interference with ATF4 increases the itch sensitivity in nonhuman primates and enhances TRPV4 currents in nonhuman primates DRG neurons; ATF4 and TRPV4 also co-expresses in human sensory neurons. Our data demonstrate that ATF4 controls pruritus by regulating TRPV4 signaling through a nontranscriptional mechanism and identifies a potential new strategy for the treatment of pathological pruritus.
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Postoperative pain is a major clinical problem imposing a significant burden on patients and society. In a survey 2 years after orthopedic surgery, 57% of patients reported persisting postoperative pain. However, only limited progress has been made in the development of safe and effective therapies to prevent the onset and chronification of pain after orthopedic surgery. ⋯ Percutaneous vagus nerve stimulation also improved locomotor coordination and accelerated bone healing. In the dorsal root ganglia, vagal stimulation inhibited the activation of glial fibrillary acidic protein-positive satellite cells but without affecting microglial activation. Overall, these data provide novel evidence supportive of the use of pVNS to prevent postoperative pain and inform translational studies to test antinociceptive effects of bioelectronic medicine in the clinic.
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Deep gluteal syndrome (DGS) is a medical diagnosis in which the pathoanatomy of the subgluteal space contributes to pain. The growing recognition that gluteal neuropathies can be associated with the presence of a bone-neural conflict with irritation or compression may allow us to shed some light on this pathology. This study aims to determine whether the location of the sciatic nerve (SN) in relation to the ischial spine (IS) contributes to the development of DGS. ⋯ The results from this study suggest that the relationship between the IS and SN may play a role in the development of DGS. This may also help establish which patients would benefit more from surgical intervention.
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Background: Diabetic nephropathy (DN) is a complication of diabetes that is the leading cause of death in diabetic patients. Circular RNA (circRNA) is a hot topic in the research of human diseases. However, the role of circ_Supt3 in DN remains unclear. ⋯ Circ_Supt3 regulated G3bp2 expression by miR-185-5p. Moreover, the circ_Supt3/miR-185-5p/G3bp2 axis regulated the cell behavior of HG-induced MPC5 cells. Conclusion: Our findings suggest that the knockdown of circ_Supt3 protects mouse MPC5 cells against HG-induced cell injury via the miR-185-5p/G3bp2 axis.
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Neuropathic pain is a type of chronic pain that entails severe prolonged sensory dysfunctions caused by a lesion of the somatosensory system. Many of those suffering from the condition do not experience significant improvement with existing medications, resulting in various side effects. In this study, Sprague-Dawley male rats were used, and long-term deep brain stimulation of the ventrolateral periaqueductal gray was conducted in a rat model of spared nerve injury. ⋯ At the spinal level, glial cells were still activated but only the 5-HT1a receptor in the spinal cord was activated, implying its inhibitory role in mechanical allodynia. This study found that peripheral neuropathy caused dysfunction in the descending serotonergic system, and prolonged stimulation of ventrolateral periaqueductal gray can modulate the pathway in an efficient manner. This work would provide new opportunities for the development of targeted and effective treatments for this debilitating disease, possibly giving us lower chances of side effects from repeated high-frequency stimulation or long-term use of medication.