Receptor-Interacting Protein Kinase 3 Inhibition Relieves Mechanical Allodynia and Suppresses NLRP3 Inflammasome and NF-κB in a Rat Model of Spinal Cord Injury.

Background: Neuroinflammation is critical in developing and maintaining neuropathic pain after spinal cord injury (SCI). The receptor-interacting protein kinase 3 (RIPK3) has been shown to promote inflammatory response by exerting its non-necroptotic functions. In this study, we explored the involvement of RIPK3 in neuropathic pain after SCI. Methods: Thoracic (T10) SCI rat model was conducted, and the mechanical threshold in rats was measured. The expressions of RIPK3, nod-like receptor family pyrin domain-containing protein 3 (NLRP3), caspase-1, and nuclear factor-κB (NF-κB) were measured with western blotting analysis or quantitative real-time polymerase chain reaction (qRT-PCR). Double immunofluorescence staining was used to explore the colabeled NLRP3 with NeuN, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (IBA1). In addition, enzyme-linked immunosorbent assay (ELISA) was applied to analyze the levels of proinflammatory factors interleukin 1 beta (IL-1ß), interleukin 18 (IL-18), and tumor necrosis factor alpha (TNF-α). Results: The expression of RIPK3 was elevated from postoperative days 7-21, which was consistent with the development of mechanical allodynia. Intrathecal administration of RIPK3 inhibitor GSK872 could alleviate the mechanical allodynia in SCI rats and reduce the expression levels of RIPK3. The activation of NLRP3 inflammasome and NF-κB was attenuated by GSK872 treatment. Furthermore, immunofluorescence suggested that NLRP3 had colocalization with glial cells and neurons in the L4-L6 spinal dorsal horns. In addition, GSK872 treatment reduced the production of inflammatory cytokines. Conclusion: Our findings indicated that RIPK3 was an important facilitated factor for SCI-induced mechanical allodynia. RIPK3 inhibition might relieve mechanical allodynia by inhibiting NLRP3 inflammasome, NF-κB, and the associated inflammation.

Comparing the efficacy and safety of short-term spinal cord stimulation and pulsed radiofrequency for zoster-related pain: A systematic review and meta-analysis.

BACKGROUND: Pulsed radiofrequency (PRF) is a commonly used method for the treatment of zoster-related pain in the clinic. However, PRF therapy has a high recurrence rate and many adverse reactions. Recent studies have shown that short-term spinal cord stimulation (stSCS) can effectively alleviate zoster-related pain. Due to the lack of evidence, it is unclear whether stSCS is superior to PRF in the efficacy of treating zoster-related pain. OBJECTIVE: This study aimed to compare the efficacy and safety of stSCS and PRF for zoster-related pain. METHODS: We searched seven electronic databases from the establishment of the database to January 2021. Related randomized controlled trials were included in this meta-analysis. After extracting the data and evaluating the methodological quality of the included trials, the outcome indicators were statistically analyzed by using RevManV.5.3. RESULTS: This meta-analysis included 6 trials with a total of 509 patients. Compared with PRF group, stSCS group showed lower pain intensity (standardized mean difference=-0.83, 95%CI [-1.37, -0.30], P=.002), better sleep quality (mean difference=-1.43, 95%CI [-2.29, -0.57], P=.001), lower pain rating index scores, and less incidence of adverse events (RR=0.32, 95%CI [0.12, 0.83], P<.05). However, the efficacies of PRF and stSCS for treating postherpetic neuralgia were consistent in the response rate (RR= 1.10, 95% CI [0.82, 1.48], P=.51) and the complete remission rate (RR=1.05, 95% CI [0.66, 1.68], P=.84). CONCLUSIONS: In this study, stSCS showed a better analgesic effect and higher safety than PRF. Our meta-analysis results suggested that stSCS may be a feasible and safe invasive treatment for zoster-related pain. However, high-quality, randomized controlled trials with large sample sizes are needed to further verify our conclusions.

Protectin DX Attenuates Lumbar Radicular Pain of Non-compressive Disc Herniation by Autophagy Flux Stimulation via Adenosine Monophosphate-Activated Protein Kinase Signaling.

Background: Neuroinflammation plays a crucial role in initiating and sustaining lumbar radicular pain (LRP). Protectin DX (PDX) has been experimentally verified to possess pro-resolving properties and anti-inflammatory effects. This study aimed to observe the analgesic effects of PDX and its potential mechanisms in LRP rats with non-compressive lumbar disc herniation (NCLDH). Method: Only male rats were selected to avoid gender-related interferences. Rat models of NCLDH were established, and rats were randomly divided into four groups: the sham group, the vehicle group, the PDX (10 ng PDX) group, and the PDX (100 ng PDX) group. Changes in the mechanical withdrawal threshold and thermal withdrawal latency were observed for 7 days. The mRNAs of pro-inflammatory and anti-inflammatory mediators were evaluated via real-time polymerase chain reaction, whereas western blot and immunohistochemistry were separately conducted to assess the expression levels of autophagy-related proteins and adenosine monophosphate-activated protein kinase (AMPK) signaling. Results: Intrathecal delivery of PDX reduced interleukin (IL)-6 and IL-1ß mRNA levels and facilitated mRNA transcription of transforming growth factor-ß1, with attenuation of mechanical and thermal hyperalgesia in LRP rat models. With the application of nucleus pulposus to the dorsal root ganglion, autophagy flux and AMPK signaling were severely disrupted in the spinal dorsal horns, and intrathecal treatment with PDX could dose-dependently restore the dysfunction of autophagy flux and AMPK signaling. Conclusion: These data suggest that PDX possesses pro-resolving properties and exerts potent analgesic effects in LRP by affecting autophagy flux via AMPK signaling.

[Study on the temperature character of the optic-fiber surface-plasmon-wave sensor].

The paper discussed the optic-fiber surface-plasmon-wave(SPW) sensor's sensitivity to temperature based on the particle vibration. For the SPW sensor consisting of metal film and dielectric, surface plasmon vibration is essentially the vibration of group electrons. Being irradiated by P light that has a special wavelength, the electrons on the surface of the metal film will absorb the power and change the way of their original movement. When the frequency of the P light is corresponded to the inherent vibration frequency of the group electrons, resonance will occur. Because the different temperature leads to different electron density--the higher the temperature the higher the density on the film surface, and because the vibration of the group electrons is correlative to the electron density closely, the temperature change will influence the inherent vibration frequency of the surface plasmon seriously. We decrease the temperature influence on the SPW by compensating the temperature change of the environment medium according to the effect. On the other hand, the paper discusses that the optic-fiber SPW sensor may be used to measure multi-parameters.