Background: Celastrol has been proven effective in anti-inflammatory but was limited in the clinic due to the poor solubility and side effects induced by low bioavailability. Osteoarthritis has acidic and inflammatory environment. Our aim was to load celastrol into HMSNs and capped with chitosan to construct a pH-responsive nanoparticle medicine (CSL@HMSNs-Cs), which is of high solubility for osteoarthritis intra-articular injection treatment. Methods: The CSL@HMSNs-Cs were assembled and the characteristics were measured. The CSL@HMSNs-Cs was applied in vitro in the chondrocytes collected from rats cartilage tissue and in vivo in the MIA induced knee osteoarthritis rats via intra-articular injection. Cytotoxicity assay, pH-responsive release, pain behavior, MRI, safranin o fast green staining, ELISA and western blot analysis were applied to evaluate the bioavailability and therapeutic effect of CSL@HMSNs-Cs. Results: CSL@HMSNs-Cs was stable due to the protection of the chitosan layers in alkaline environment (pH = 7.7) but revealed good solubility and therapeutic effect in acidic environment (pH = 6.0). The cytotoxicity assay showed no cytotoxicity at relatively low concentration (200 μg/mL) and the cell viability of chondrocytes stimulated by IL-1β was increased in CSL@HMSNs-Cs group. Paw withdrawal threshold in CSL@HMSNs-Cs group is increased, and MRI and Safranin O Fast Green staining showed improvements in articular surface erosion and joint effusion. The upregulated expression levels of IL-1β, TNF-α, IL-6, MMP-3 and MMP-13 and NF-κB signaling pathway of chondrocytes were inhibited in CSL@HMSNs-Cs group. Conclusion: Hollow mesoporous silica nanoparticles were an ideal carrier for natural drugs with poor solubility and were of high biocompatibility for intra-articular injection. These intra-articular injectable CSL@HMSNs-Cs with improved solubility, present a pH-responsive therapeutic strategy against osteoarthritis.

Chronic nonspecific low back pain (CNLBP) is defined as pain or discomfort originating from the waist, which lasts for at least 12 weeks, but no radiculopathy or specific spinal diseases. CNLBP is a complicated medical problem and places a huge burden on healthcare systems. Clinical manifestation of CNLBP includes discogenic LBP, zygapophyseal joint pain, sacroiliac joint pain, and lumbar muscle strain. Further evaluation should be completed to confirm the diagnosis including auxiliary examination, functional assessment, and clinical assessment. The principle of the management is to relieve pain, restore function, and avoid recurrence. Treatment includes conservative treatment, minimally invasive treatment, and rehabilitation. Pharmacologic therapy is the first-line treatment of nonspecific LBP, and it is most widely used in clinical practice. Interventional therapy should be considered only after failure of medication and physical therapy. Multidisciplinary rehabilitation can improve physical function and alleviate short-term and long-term pain. The emphasis should be put on the prevention of NLBP and reducing relevant risk factors.

Background: Although the interaction between pain and cognition has been recognized for decades, the neural substrates underlying their association remain unclear. The prefrontal cortex (PFC) is known as a critical brain area for higher cognitive functions, as well as for pain perception and modulation. The objective of the present study was to explore the role of the PFC in the interaction between chronic pain and cognitive functions by examining the relationship between spontaneous activity in the frontal lobe and pain intensity reported by postherpetic neuralgia (PHN) patients. Methods: Resting-state functional magnetic resonance imaging data from 16 PHN patients were collected, and regional homogeneity and related functional connectivity were analyzed. Results: The results showed negative correlations between patients’ pain scores and regional homogeneity values in several prefrontal areas, including the left lateral PFC, left medial PFC, and right lateral orbitofrontal cortex (P<0.05, AlphaSim-corrected). Further analysis revealed that the functional connectivity of some of these prefrontal areas with other cortical regions was also modulated by pain intensity. Therefore, functional connections of the left lateral PFC with both the left parietal cortex and the left occipital cortex were correlated with patients’ pain ratings (P<0.05, AlphaSim-corrected). Similarly, functional connectivity between the right lateral orbitofrontal cortex and bilateral postcentral/precentral gyri was also correlated with pain intensity in the patients (P<0.05, AlphaSim-corrected). Conclusion: Our findings indicate that activity in the PFC is modulated by chronic pain in PHN patients. The pain-related modulation of prefrontal activity may serve as the neural basis for interactions between chronic pain and cognitive functions, which may link to cognitive impairments observed in chronic pain patients.

Background: Postherpetic neuralgia (PHN) is common in elderly patients and can be alleviated by pulsed radiofrequency (PRF). However, PRF treatments display different efficacy on different nerves. The purpose of this study was to evaluate the efficacy and safety of ultrasound-guided PRF modulation on thoracic dorsal root ganglion (DRG) or intercostal nerve (ICN) for PHN in aged patients and to provide a theoretical basis for clinical treatment. Methods: We classified aged patients into two groups, DRG group and ICN group, based on the needle tip position. Visual analogue scale (VAS) and concise health status questionnaire (Short-form 36 health/survey questionnaire, SF-36) were used to evaluate the pain intensity and the life quality of the patients before and 2, 4 and 12 weeks after the PRF treatments. We also recorded the adverse reactions during the treatments. Results: After the PRF treatment, the scores of VAS and SF-36 (assessing general health perception, social function, emotional role, mental health, and pain) improved significantly in both groups (P < 0.05). The mean VAS score in the DRG group was significantly lower than that in the ICN group 2 weeks after treatment, and remained for 12 weeks. The SF-36 scores in the DRG group were significantly higher than those in the ICN group (P < 0.05). We found a similar incidence of adverse reactions between the two groups (P > 0.05). Conclusions: PRF therapy is safe and effective for elderly patients with postherpetic neuralgia. However, PRF treatment in dorsal root ganglion is superior to that in intercostal nerve with improving VAS and SF-36 scores to a greater extent in older patients. Trial registration: ChiCTR2100044176.