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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.

Toll-like receptors (TLRs) play a pivotal role in the defense against invading pathogens by detecting pathogen-associated molecular patterns (PAMPs). TLR4 recognizes lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria, resulting in the induction and secretion of proinflammatory cytokines such as TNF-α and IL-6. The WW domain containing E3 ubiquitin protein ligase 1 (WWP1) regulates a variety of cellular biological processes. Here, we investigated whether WWP1 acts as an E3 ubiquitin ligase in TLR-mediated inflammation.Knocking down WWP1 enhanced the TNF-α and IL-6 production induced by LPS, and over-expression of WWP1 inhibited the TNF-α and IL-6 production induced by LPS, but not by TNF-α. WWP1 also inhibited the IκB-α, NF-κB, and MAPK activation stimulated by LPS. Additionally, WWP1 could degrade TRAF6, but not IRAK1, in the proteasome pathway, and knocking down WWP1 reduced the LPS-induced K48-linked, but not K63-linked, polyubiquitination of endogenous TRAF6.We identified WWP1 as an important negative regulator of TLR4-mediated TNF-α and IL-6 production. We also showed that WWP1 functions as an E3 ligase when cells are stimulated with LPS by binding to TRAF6 and promoting K48-linked polyubiquitination. This results in the proteasomal degradation of TRAF6.

The aim of the present study was to evaluate the therapeutic potential of sesamol treatment on focal ischemia/reperfusion (I/R) injury in the rat brain. The results demonstrated that pretreatment with sesamol seven days prior to focal cerebral I/R injury had significant positive effects, including improvements in neurological deficits (P<0.05), and a reduction in malondialdehyde content and elevation of antioxidant levels (superoxide dismutase, glutathione and glutatione peroxidase; both P<0.05). Furthermore, levels of B cell lymphoma-2 (Bcl-2)-associated X protein and caspase-3 were significantly downregulated, whereas the level of Bcl-2 was effectively increased. Conversely, the mRNA expression of proinflammatory cytokines were significantly reduced in focal cerebral I/R injury rats upon sesamol intervention. Therefore, the beneficial effects of sesamol on cerebral I/R injury may be due to the reduction of oxidative stress, inhibition of apoptosis and inflammation. The findings of the present study suggest that sesamol supplementation may serve as potent adjuvant in the treatment of focal cerebral ischemia/reperfusion injury due to its neuroprotective effects. [ABSTRACT FROM AUTHOR]

Cancer-induced bone pain can severely compromise the life quality of patients, while tolerance limits the use of opioids in the treatment of cancer pain. Monocyte chemoattractant protein-1 (MCP-1) is known to contribute to neuropathic pain. However, the role of spinal MCP-1 in the development of morphine tolerance in patients with cancer-induced bone pain remains unclear. The aim of the present study was to investigate the role of spinal MCP-1 in morphine tolerance in bone cancer pain rats (MTBP rats). Bone cancer pain was induced by intramedullary injection of Walker 256 cells into the tibia of the rats, while morphine tolerance was induced by continuous intrathecal injection of morphine over a period of 9 days. In addition, anti-MCP-1 antibodies were intrathecally injected to rats in various groups in order to investigate the association of MCP-1 with mechanical and heat hyperalgesia using the paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) tests, respectively. Furthermore, MCP-1 and CCR2 expression levels were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, and CCR2 expression levels were measured using RT-qPCR. The results indicated that MCP-1 and CCR2 expression levels were significantly increased in the spinal cord of MTBP rats. Intrathecal administration of anti-MCP-1 neutralizing antibodies was observed to attenuate the mechanical and thermal allodynia in MTBP rats. Therefore, the upregulation of spinal MCP-1 and CCR2 expression levels may contribute to the development of mechanical allodynia in MTBP rats. In conclusion, MCP-1/CCR2 signaling may serve a crucial role in morphine tolerance development in rats suffering from cancer-induced bone pain. [ABSTRACT FROM AUTHOR]

Objective: The present study sought to detect spinal sirtuin 1 (SIRT1) and acetylation of histone H3 (Ac-H3) expression in rats with burn injury pain (BIP model). Procedures and Results: A BIP model was first established. BIP rats showed lower paw withdrawal threshold (PWT) from day 1, which persisted for 21 days following the burn injury. Spinal SIRT1/Ac-H3 expression increased following burn injury. The intrathecal use of resveratrol increased PWT and SIRT1 expression but induced down-regulation of Ac-H3 expression. We first demonstrated that the inhibition of SIRT1 significantly induced mechanical allodynia in naïve rats. The preinjection of SIRT1 inhibitor partly antagonized the analgesic effects of resveratrol in BIP rats. Conclusion: Inhibition of SIRT1 produces pain facilitation in the naïve rats. The expression of spinal SIRT1 increased after burn injury in the BIP model. The activation of spinal SIRT1 might mediate the resveratrol-induced analgesic effects. [ABSTRACT FROM AUTHOR]

Background: Conventional hyperbaric spinal anaesthesia solution (SAS) with 8% glucose and low-dose bupivacaine may reduce the incidence of hypotension in caesarean section compared to standard doses, and marginally hyperbaric SAS (≤0.8% glucose) can induce a lower block level and a lower incidence of hypotension in nonobstetric patients than conventional 8% glucose SAS.Objective: The objective of this study was to evaluate the clinical efficacy of marginally hyperbaric low-dose bupivacaine solutions used for spinal anaesthesia during caesarean section.Design: A randomised, controlled clinical trial.Setting: Single medical centre.Patients: One hundred twenty women scheduled for elective caesarean section were randomised into four groups.Interventions: Caesarean section after combined spinal-epidural anaesthesia using hyperbaric preparations of low-dose SAS (7.2 mg bupivacaine and 2 μg 1.6 ml sufentanil in one of the following: 8%, 0.8%, 0.5% or 0.33% glucose solution.Main Outcome Measures: The dermatomal sensory block and degree of motor block of the lower extremities and adverse effects of anaesthesia were recorded.Results: The maximum cephalad sensory block level and the incidence of hypotension decreased as the density of SAS fell (T1, T2, T4 and T6, P < 0.001; 48.3, 30, 13.3 and 10.3%, P = 0.003). The incidence of shivering reduced with decreasing density of SAS (P < 0.05). There was no significant difference in the quality of anaesthesia (efficacy of motor block and sensory block) between the groups (P > 0.05).Conclusion: Compared with conventional 8% glucose hyperbaric SAS, marginally hyperbaric (0.5 or 0.33% glucose) low-dose bupivacaine solutions led to a significantly lower height of cephalad spread and incidence of hypotension with no impact on the efficacy of spinal anaesthesia for caesarean section. [ABSTRACT FROM AUTHOR]

The mechanisms of collision avoidance (CA) behaviours in interweaving pedestrian flow movements are important for pedestrian space planning and emergency management but not well understood yet. In this paper, a series of controlled interweaving pedestrian flow experiments with different densities are carried out to investigate the CA behaviours, especially CA strategy choices. Four types of CA strategies are manually identified in these experiments. Nine characteristic parameters based on the trajectory data are defined to explore the characteristics of CA behaviours. The experimental results reveal that (i) the CA behaviours change with density levels; (ii) heterogeneities can be found for individual pedestrians; (iii) the defined characteristic parameters show different statistical features for different types of CA strategies, and correlations exist between most of the parameter pairs; (iv) it usually takes 0.5–2.5 s to complete a CA process with a trajectory length of 0.5–3.5 m. A multi-nomial logit (MNL) model and a long-short-term-memory (LSTM) model are established respectively for predicting pedestrians' choices of CA strategies using the selected characteristic parameters as inputs. The modelling results prove the importance of using time-series data for pedestrian behaviour modelling, and the LSTM models show advantages over the MNL model at this point.