Studies showed that upregulation of Nav1.6 increased the neuronal excitability and participated in neuropathic pain in the dorsal root ganglion (DRG). However, the molecular mechanisms underlying Nav1.6 upregulation were not reported yet. The paw withdrawal threshold was measured in the rodents following lumbar 5 ventral root transection (L5-VRT). Then qPCR, western blotting, immunoprecipitation, immunohistochemistry, and chromatin immunoprecipitation assays were performed to explore the molecular mechanisms in vivo and in vitro. We found that the levels of Nav1.6 and phosphorylated STAT3 were significantly increased in DRG neurons following L5-VRT, and TNF-α incubation also upregulated the Nav1.6 expression in cultured DRG neurons. Furthermore, immunoprecipitation and chromatin immunoprecipitation assays demonstrated that L5-VRT increased the binding of STAT3 to the Scn8a (encoding Nav1.6) promoter and the interaction between STAT3 and p300, which contributed to the enhanced transcription of Scn8a by increasing histone H4 acetylation in Scn8a promoter in DRG. Importantly, intraperitoneal injection of the TNF-α inhibitor thalidomide reduced the phosphorylation of STAT3 and decreased the recruitment of STAT3 and histone H4 hyperacetylation in the Scn8a promoter, thus subsequently attenuating Nav1.6 upregulation in DRG neurons and mechanical allodynia induced by L5-VRT. These results suggested a new mechanism for Nav1.6 upregulation involving TNF-α/STAT3 pathway activation and subsequent STAT3-mediated histone H4 hyperacetylation in the Scn8a promoter region in DRG, which contributed to L5-VRT-induced neuropathic pain.
Transforaminal steroid injection is extensively used as a treatment in cases of herniated disc, but it is associated with complications. In comparison, platelet-rich plasma (PRP) injection has been used in musculoskeletal disorders and could be another option. This study is aimed at comparing the efficacy and safety aspects between ultrasound-guided transforaminal injections of PRP and steroid in patients who suffer from radicular pain due to lumbar disc herniation. In a randomized controlled trial, ultrasound-guided transforaminal injections of either PRP ( ) or steroid ( ) were administered to a total of 124 patients who suffer from radicular pain due to lumbar disc herniation. Patients were assessed by the visual analogue scale (VAS), pressure pain thresholds (PPTs), Oswestry disability index (ODI), and the physical function (PF) and bodily pain (BP) domains of the 36-item short form health survey (SF-36) before operation and 1 week, 1 month, 3 months, 6 months, and 12 months after operation. The rate and latency of F-wave were obtained before operation and 12 months postoperation. There was no statistical difference in terms of age and sex between both groups. Statistically significant improvements from the patients’ data before operation to data obtained 1-month postoperation were observed in VAS, PPTs, ODI, and PF and BP of SF-36 in both groups and kept for 1 year. F-wave rate and latency were improved significantly at 1-year postoperation in both groups. Intergroup differences during follow-ups over a period of 1 year were not found to be significant in all the above assessment between the PRP and steroid groups. No complications were reported. The results showed similar outcome for both transforaminal injections using PRP and steroid in the treatment of lumbar disc herniation, suggesting the possible application of PRP injection as a safer alternative. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-INR-17011825).
This study compared the result of percutaneous release using a miniscalpel-needle and steroid injection in 93 trigger thumbs in 83 patients. The patients were randomly assigned to either miniscalpel-needle percutaneous release (group A) or steroid injection (group B). Visual analogue pain scales and patients’ satisfaction were evaluated at baseline, 1 and 12 months. One patient in group A and two patients in group B were lost to follow-up. Forty-four of the 46 trigger thumbs in group A and 12 of 47 trigger thumbs in group B had satisfactory results at 12 months. No digital nerve injury occurred in either group. Percutaneous release with a miniscalpel-needle had a higher success rate than steroid injection.
Trigeminal nerve stimulation (TNS) has been proposed as a promising intervention for coma awakening. However, the effect of TNS on patients with prolonged disorders of consciousness (pDoC) is still unclear. This study aimed to investigate the therapeutic effects of TNS in pDoC caused by stroke, trauma, and anoxia. A total of 60 patients (male =25, female =35) aged over 18 who were in a vegetative state or minimally conscious state were randomly assigned to the TNS (N = 30) or sham TNS (N = 30) groups. 4 weeks of intervention and a followed up for 8 weeks were performed. The Glasgow Coma Scale (GCS) and Coma Recovery Scale-Revised (CRS-R) scores as primary outcomes were assessed at baseline and at 2, 4, 8, and 12 weeks. The score changes in the TNS group over time for CRS-R (2-week: mean difference = 0.9, 95% CI = [0.3, 1.5], P = 0.006; 4-week: 1.6, 95% CI = [0.8, 2.5], P < 0.001; 8-week: mean difference = 2.4, 95% CI = [1.3, 3.5], P < 0.001; 12-week: mean difference = 2.3, 95% CI = [1.1, 3.4], P < 0.001) and GCS (4-week: mean difference = 0.7, 95% CI = [0.3, 1.2], P = 0.002; 8-week: mean difference = 1.1, 95% CI = [0.6, 1.7], P < 0.001; 12-week: 1.1, 95% CI = [0.5, 1.7], P = 0.003) were higher than those in the sham group. 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) revealed that the metabolism of the right parahippocampal cortex, right precuneus, and bilateral middle cingulate cortex was significantly increased in TNS group. The results of this study indicate that TNS could increase local brain metabolism and may promote functional recovery in patients with prolonged disorders of consciousness. Name of the registry: Chinese Clinical Trial Registry. ChiCTR1900025573. The date that the study was submitted to a registry: 2019-09-01. The date when the first patient was enrolled was 2021-01-20.