Etanercept decreases HMGB1 expression in dorsal root ganglion neuron cells in a rat chronic constriction injury model.

In the present study, we examined the effect of etanercept on high mobility group box 1 (HMGB1) expression in dorsal root ganglion (DRG) neuron cells in a rat model of chronic constriction injury (CCI) of the sciatic nerve, with the aim of exploring the molecular mechanism underlying the therapeutic effect of etanercept on sciatica-related nociception and the potential interaction between tumor necrosis factor-α (TNF-α) and HMGB1 in DRG neuron cells. A rat CCI model was employed and the animals were randomly assigned to seven groups (n=20/group): untreated, sham only, sham/saline, sham/etanercept, CCI only, CCI/saline and CCI/etanercept. Our results revealed that compared with the sham/saline and sham/etanercept groups, thermal hyperalgesia and mechanical hyperalgesia, as well as HMGB1 expression at both the mRNA and protein levels in the DRG neuron cells, were induced by CCI, and were significantly inhibited by etanercept. Although etanercept showed no significant effect on the sham group, it significantly reduced the phosphorylated p38 mitogen-activated protein kinase (MAPK) levels induced by CCI in the DRG neuron cells. In conclusion, we demonstrated that etanercept significantly decreased the HMGB1 expression induced by CCI in the DRG neuron cells. This study not only explored the molecular mechanisms underlying the therapeutic effect of etanercept on sciatica-related nociception, but also provided indirect evidence for an interaction between TNF-α and HMGB1 in DRG neuron cells.

Intrathecal infusion of pyrrolidine dithiocarbamate for the prevention and reversal of neuropathic pain in rats using a sciatic chronic constriction injury model.

BACKGROUND AND OBJECTIVES: Recent studies have suggested that nuclear factor κB (NF-κB) may play a role in mediating nerve injury-induced neuropathic pain. Here, we examined the effects of intrathecal pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor, on the development of neuropathic pain, spinal microglial activation, and CX3CR1 expression induced by sciatic chronic constriction injury (CCI) model in rats. METHODS: Under chloral hydrate anesthesia, male Sprague-Dawley rats (300-350 g) fitted with intrathecal catheters underwent either sciatic CCI or sham surgery. Intrathecal saline or PDTC (100 or 1000 pmol/d) was infused 1 day before or 3 days after CCI (n = 8). The rat hind-paw withdrawal threshold to mechanical stimuli and withdrawal latency to radiant heat were determined before surgery and from days 1 to 7 after CCI. Spinal microglial activation was evaluated with OX-42 immunoreactivity, and spinal CX3CR1 expression was assessed by Western blotting. RESULTS: Chronic constriction injury induced mechanical allodynia and thermal hyperalgesia and microglial activation as demonstrated by OX-42 expression. Whereas it had no apparent effect on spinal cord histology, intrathecal administration of PDTC prevented the development of the mechanical and thermal hyperalgesia and inhibited nerve injury-induced microglial activation and spinal CX3CR1 expression. CONCLUSIONS: In this study, we have shown the protective effect of intrathecal PDTC on the development of nociceptive behaviors induced by CCI in rats. The activation of NF-κB pathway may contribute to spinal microglial activation and CX3CR1 up-regulation.

[Cerebral state index the in monitoring and evaluating the induction of anesthesia with target-controlled infusion of propofol in adults].

OBJECTIVE: To evaluate the accuracy of cerebral state index (CSI) as an indicator of anesthesia depth in patients in the induction of anesthesia with target-controlled infusion of propofol. METHODS: Forty ASA (American Society of Anesthesiologists) I approximately II patients scheduled for an operation under general anesthesia were anesthetized with target-controlled infusion of propofol. Target plasma concentration was 0. 5 mg/L at the beginning, and increased by 0. 5 mg/L every 5 minutes, till 5 minutes after the level of MOAA/S (modified observer's assessment of alertness/sedation) was 0. The CSI, mean arterial pressure (MAP), heart rate (HR), MOAA/S level, and the effect-site concentration of propofol were recorded. RESULTS: (1) CSI values declined with the decrease of MOAA/S levels. CSI values were statistically different between level 0 and 1, level 1 and 2, level 3 and 4, level 4 and 5 of MOAA/S (P < 0.05). The difference of MAP had statistical significance between level 3 and level 2 of MOAA/S (P < 0.05). HR values had no statistical difference between the two levels of MOAA/S (P > 0.05). (2) The spearman rank correlation co-efficients between CSI, MAP, HR and the level of MOAA/S were 0.929, 0.421, and 0.085, respectively. The prediction probabilities (Pk) to differentiate different levels of MOAA/S for CSI, MAP, and HR were 0.94, 0.67, and 0.54, respectively. (3) There was linear regression relationship between CSI and the effect-site concentration of propofol (the coefficient of determination R2 was 0. 833, P < 0.01). CONCLUSION: During the induction of patients with target-controlled infusion of propofol, the CSI is accurate as an indicator of awakeness and different levels of consciousness after anesthesia, and can reliably predict the anesthesia depth.

[Bispectral index, cerebral state index and the predicted effect-site concentration at different clinical end-points during target-controlled infusion of propofol].

OBJECTIVE: To examine the predicted effect-site concentration of propofol at two clinical end-points: loss of verbal contact (LVC) and loss of consciousness (LOC), and to explore the relationship between bispectral index (BIS) values, cerebral state index (CSI) values and the predicted effect-site concentration during the target-controlled infusion of propofol. METHODS: In 20 patients during the target-controlled infusion of propofol, the propofol infusion was set at an initial effect-site concentration of 0.5 mg/L, and increased by 0.5 mg/L every 5 min until 5 min after the modified observer's assessment of alertness/sedation scale (OAA/S) values reached zero. The predicted effect-site concentration of propofol, the values of CSI and BIS were recorded, and the sedation level was examined by the modified OAA/S every 20s. The predicted effect-site concentrations of propofol in target-controlled infusion (TCI) system were recorded when they increased by more than 0.1 mg/L. The predicted effect-site concentrations of propofol and the values of BIS and CSI at LVC and LOC in 5%, 50% and 95% of the patients were calculated. RESULTS: There was good linearity between BIS and the predicted effect-site concentration of propofol (R(2)=0.787), as well as between CSI and the predicted effect-site concentration of propofol (R(2)=0.792). The predicted effect-site concentrations of propofol at LVC in 5%, 50% and 95% of the patients were 1.1,1.8 and 2.4 mg/L, respectively. The values of BIS and CSI at LVC in 5%, 50% and 95% of the patients were 79.2, 69.2 and 59.2; 74.9, 65.9 and 56.8, respectively. The predicted effect-site concentrations of propofol at LOC in 5%, 50% and 95% of the patients were 1.5, 2.5 and 3.4 mg/L, respectively. At LOC, the values of BIS and CSI in 5%, 50% and 95% of the patient were 73.6, 57.1 and 40.6; 65.2, 54.8 and 44.3, respectively. CONCLUSION: During target-controlled infusion of propofol, LVC and LOC occur within a definite range of predicted effect-site concentrations. There is the good linearity between BIS, CSI and the predicted effect-site concentrations of propofol. CSI may be more useful than BIS in predicting LVC and LOC.