Background:
Neuroinflammation and cytokines play critical roles in neuropathic pain and axon degeneration/regeneration. Cytokines of transforming growth factor-β superfamily have implications in pain and injured nerve repair processing. However, the transcriptional profiles of the transforming growth factor-β superfamily members in dorsal root ganglia under neuropathic pain and axon degeneration/regeneration conditions remain elusive.
Objective:
We aimed to plot the transcriptional profiles of transforming growth factor-β superfamily components in lumbar dorsal root ganglia of nerve axotomized rats and to further verify the profiles by testing the analgesic effect of activin C, a representative cytokine, on neuropathic pain.
Methods:
Adult male rats were axotomized in sciatic nerves and lumbar dorsal root ganglia were isolated for total RNA extraction or section. A custom microarray was developed and employed to plot the gene expression profiles of transforming growth factor-β superfamily components. Real-time RT-PCR was used to confirm changes in the expression of activin/inhibin family genes, and then in situ hybridization was performed to determine the cellular locations of activin βC mRNAs. Rat spared nerve injury model was performed and pain test was employed to determine the effect of activin C on neuropathic pain.
Results:
The expression of transforming growth factor-β superfamily cytokines and their signaling, including some receptors and signaling adaptors, were robustly upregulated. Activin βC subunit mRNAs were expressed in the small-diameter dorsal root ganglion neurons and upregulated after axotomy. Single intrathecal injection of activin C inhibited neuropathic pain in spared nerve injury model.
Conclusion:
This is the first report to investigate the transcriptional profiles of members of transforming growth factor-β superfamily in axotomized dorsal root ganglia. The distinct cytokine profiles observed here might provide clues toward further study of the role of transforming growth factor-β superfamily in the pathogenesis of neuropathic pain and axon degeneration/regeneration after peripheral nerve injury.
The myeloid differentiation factor 88 (MyD88) adaptor mediates signaling by Toll-like receptors and some interleukins (ILs) in neural and non-neuronal cells. Recently, MyD88 protein was found to express in primary sensory neurons and be involved in the maintenance of persistent pain induced by complete Freund’s adjuvant, chronic constriction injury and chemotherapy treatment in rodents. However, whether MyD88 in nociceptive neurons contributes to persistent pain induced by intraplantar injection of formalin remains elusive. Here, using conditional knockout (CKO) mice, we found that selective deletion of Myd88 in Nav1.8-expressing primary nociceptive neurons led to reduced pain response in the recovery phase of 1% formalin-induced mechanical pain and impaired the persistent thermal pain. Moreover, CKO mice exhibited reduced phase II pain response in 1%, but not 5%, formalin-induced acute inflammatory pain. Finally, nociceptor MyD88 deletion resulted in less neuronal c-Fos activation in spinal dorsal horns following 1% formalin stimulation. These data suggest that MyD88 in nociceptive neurons is not only involved in persistent mechanical pain but also promotes the transition from acute inflammatory pain to persistent thermal hyperalgesia induced by low-dose formalin stimulation.
To explore the effects of the project-achievement quality control circle in constructing a new health education model for patients with chronic hepatitis B.
The quality control circle group was established and the theme of “constructing a new health education model for patients with chronic hepatitis B” was selected. The circle staff determined that this quality control circle was of project-achievement according to the quality control story judgment table, and then carry out activities in strict accordance with the 10 steps of project-achievement quality control circle, evaluate the tangible results and non-tangible results before and after the activity.
After the implementation of the activity, the health education integrity of patients with chronic hepatitis B increased from 74.75 ± 11.00 to 95.00 ± 5.55 points (
P
< .001). The awareness of health education increased from 71.90 ± 13.48 to 95.60 ± 2.84 points (
P
< .001), the satisfaction rate of health education increased from 76.60 ± 8.71 points to 98.00 ± 2.03 points (
P
< .001), and the evaluation rate after health education increased from 10% to 100% (
P
< .001).
The circle members have much more confidence in quality control circle activities, the use of techniques, and the knowledge related to scientific research.
Spatio-temporal specific lncRNAs play important regulatory roles not only in the growth and development of the brain but also in the occurrence and development of neurological diseases. Generally, the occurrence of neurological diseases is accompanied by neuroinflammation. Elucidation of the regulatory mechanisms of lncRNAs on neuroinflammation is helpful for the clinical treatment of neurological diseases. This paper focuses on recent findings on the regulatory effect of lncRNAs on neuroinflammatory diseases and selects ten lncRNAs that have been intensively studied to analyze their mechanism of action.The clinical treatment status of lncRNAs as drug targets is also reviewed.
Significance StatementGene therapies such as CRISPR/Cas9 technology, antisense RNA technology and RNAi technology are gradually applied in clinical treatment, and the development of technology is based on a large number of basic research investigations. This paper focuses on the mechanisms of lncRNAs regulation of neuroinflammation, elucidates the beneficial or harmful effects of lncRNAs in neurosystemic diseases, and provides theoretical bases for lncRNAs as drug targets.
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