Effects of different transcranial magnetic stimulations on neuropathic pain after spinal cord injury.

Introduction: Repetitive transcranial magnetic stimulation (rTMS) is an effective non-invasive cortical stimulation technique in the treatment of neuropathic pain. As a new rTMS technique, intermittent theta burst stimulation (iTBS) is also effective at relieving pain. We aimed to establish the pain-relieving effectiveness of different modalities on neuropathic pain. The study was conducted in individuals with spinal cord injury (SCI) and different modalities of rTMS. Methods: Thirty-seven individuals with SCI were randomly allocated to three groups, in which the "iTBS" group received iTBS, the "rTMS" group received 10 Hz rTMS, and the "iTBS + rTMS" group received iTBS and 10 Hz rTMS successively of the primary motor cortex 5 days a week for 4 weeks, and they all underwent the full procedures. The primary outcome measure was change in the visual analog scale (VAS), and the secondary outcomes were measured using the Hamilton Rating Scale for Depression (HAM-D) and the Pittsburgh Sleep Quality Index (PSQI). All the outcomes were evaluated at 1 day before stimulation (baseline), 1 day after the first week of stimulation (S1), and 1 day after the last stimulation (S2). Results: The VAS scores showed significant pain improvement after 4 weeks of stimulation (p = 0.0396, p = 0.0396, and p = 0.0309, respectively) but not after 1 week of stimulation. HAM-D scores declined, but the decreases were not significant until 4 weeks later (p = 0.0444, p = 0.0315, and p = 0.0447, respectively). PSQI scores were also significantly decreased after 4 weeks of stimulation (p = 0.0446, p = 0.0244, and p = 0.0088, respectively). Comparing the three modalities, VAS, HAM-D, and PSQI scores at S1 showed no differences, and, at S2, VAS scores showed significant differences (p = 0.0120; multiple comparisons showed significant differences between iTBS and iTBS + rTMS, p = 0.0091), while the HAM-D and PSQI scores showed no differences. Discussion: The primary and secondary outcomes all showed significant improvement, indicating that the three different modalities were all effective at relieving the pain. However, not all the three stimulations were of same effectiveness after treatment; there were statistical differences in the treatment of neuropathic pain between iTBS as a priming stimulus and as a single procedure.

The efficacy and safety of intra-articular botulinum toxin type A injection for knee osteoarthritis: A meta-analysis of randomized controlled trials.

The purpose of this study was to investigate the efficacy and safety of intra-articular Botulinum Toxin type A (BTA) injection in the management of patients with knee osteoarthritis (KOA). The literature retrieval was conducted based on PRISMA guidelines. Databases including Pubmed, Web of science, EMBASE, and Cochrane Library were searched to identify RCTs that comparing the effects of intra-articular BTA injection with control interventions on patients with KOA. The primary outcomes involved pain and function improvements as well as the occurrence of adverse events. Seven RCTs comprising 548 participants were included in this meta-analysis. Compared with the control group, BTA injection exhibited greater pain reduction at 4 weeks posttreatment (SMD = -0.86, 95% CI [-1.52, -0.19], p = 0.011), but not 8-24 weeks posttreatment (wk 8, SMD = -0.53, 95% CI [-1.21, 0.15], p = 0.127; wk 12, SMD = -0.34, 95% CI [-0.73, 0.04], p = 0.081; wk 24, SMD = -0.65, 95% CI [-1.52, 0.22], p = 0.144). Additionally, no differences were found between BTA injection versus control intervention on functional improvement at all time points assessed (wk 4, WMD = -5.16, 95% CI [-12.31, 2.00], p = 0.158; wk 8, WMD = -0.98, 95% CI [-5.66, 3.71], p = 0.683; wk 12, WMD = -2.52, 95% CI [-7.54, 2.50], p = 0.325); wk 24, WMD = -3.66, 95% CI [-14.09, 6.76], p = 0.491). There was no significant difference in adverse event rate between the BTA and control group (OR = 0.88, 95% CI [0.24, 3.18], p = 0.843). This meta-analysis suggests that intra-articular BTA injection could be an efficious and safe strategy for analgesic treatment of KOA. However, evidence is limited due to the small number and heterogeneity of included studies, this urges further and stronger trials to confirm our findings.

K-3-Rh Protects Against Cerebral Ischemia/Reperfusion Injury by Anti-Apoptotic Effect Through PI3K-Akt Signaling Pathway in Rat.

BACKGROUND/AIMS: Ischemic stroke is the main cause of nerve damage and brain dysfunction, accompanied by strong brain cell apoptosis. This study aimed to investigate the effect of kaempferol-3-O-rhamnoside (K-3-rh) on cerebral ischemia-reperfusion (I/R) injury. METHODS AND MATERIALS: A rat model of cerebral I/R injury was established. The effects of K-3-rh on cerebral infarction size, brain water content and neurological deficits in rats were evaluated. Apoptosis of ischemic brain cells after mouse I/R was observed by TUNEL staining and flow cytometry. Western blot and qRT-PCR were used to detect the effect of K-3-rh on the expression of apoptosis-related proteins. RESULTS: K-3-rh can improve the neurological deficit score, reduce the infarct volume and brain water content, and inhibit cell apoptosis. In addition, K-3-rh significantly downregulated the expression of Bax and p53 and upregulated the expression of Bcl-2, and the phosphorylation level of Akt. Blockade of PI3K activity by the PI3K inhibitor wortmannin not only reversed the effects of K-3-rh on infarct volume and brain water content but also reversed the expression level of p-Akt. CONCLUSION: K-3-rh had obvious neuroprotective effects on brain I/R injury and neuronal apoptosis, and its mechanism may be related to activation of PI3K/Akt signaling pathway.

Intra-articular injection of Botulinum toxin A reduces neurogenic inflammation in CFA-induced arthritic rat model.

Currently, administration of Botulinum toxin Type A (BoNT/A) to treat arthritic pain has promising efficacy in clinical research. However, the mechanisms underlying anti-neurogenic inflammation mediated by BoNT/A remains unclear. The aim of this study was to demonstrate the effectiveness in macro and micro levels and to explore the causal mechanism of BoNT/A. Wistar rats (n = 60) were injected with 50ul complete Freund's adjuvant (CFA) in the left ankle joint capsule to establish a model of chronic monoarthritis. Pain behaviour (Evoked pain assessment) and infrared thermal imaging testing were performed at the macroscopic level to assess the effectiveness of analgesia and anti-inflammation. Western blotting and immunofluorescence staining were used at the microscopic level in an attempt to determine the mechanisms of anti-nociceptive or anti-inflammatory effects of BoNT/A. Additionally, hematoxylin-eosin staining was also used to visualise the cartilage and the synovial degenerative conditions of arthritis. By comparing the outcome of the evoked pain test and immunofluorescence staining, there was a significant improvement in BoNT/A compared with the normal saline (NS) injected control group. In addition, thermal variations showed that the temperature of ipsilateral ankle joint increased between 1 and 2 weeks following injection of CFA, but decreased after 3 weeks (still above the contralateral side). However, the temperature showed no difference between the BoNT/A group and NS group after treatment. The expression of IL-1ß or TNF-α in the ankle synovial tissue was significantly decreased in the BoNT/A group compared to the NS group (p < 0.05). Based on the HE assessment, cartilage degeneration and infiltration of inflammatory cells in the BoNT/A group was alleviated compared to the NS group after treatment. In conclusion, we proposed the hypothesis that intra-articular BoNT/A administration does play an important role in anti-neurogenic inflammation. The possible mechanisms might be that BoNT/A prevents the release of nociceptive nerve peptides at the injection site and then suppresses the expression of inflammatory cytokines.