Nerve injury-related autoimmunity activation leads to chronic inflammation and chronic neuropathic pain.

BACKGROUND: Peripheral nerve injuries that provoke neuropathic pain are associated with chronic inflammation and nervous lesions. The authors hypothesized that chronic neuropathic pain might be caused by chronic inflammation resulting from a nervous autoimmune reaction triggered by nerve injury. METHODS: The authors observed chronic inflammation and neuropathic behaviors for up to 12 weeks after nerve injury in T lymphocyte-deficient nude mice and their heterozygous littermates. Lymphocyte proliferation and Schwann cell apoptosis were examined after coculture of each population with various neural tissues from normal rats and those with nerve injury. RESULT: Nude mice recovered faster and exhibited less thermal hyperalgesia after nerve injury compared to their heterozygous littermates. A large number of IL-17 cells indicative of lymphocyte activation were found in the injured sciatic nerve and spinal cord (L4-6) of heterozygous littermates, but far fewer of these populations were found in nude mice. In vitro lymphocyte proliferation was enhanced after coculture with nerve tissues from normal rats compared to nerve tissue-free phosphate-buffered saline controls. In particular, coculture with sciatic nerve tissue enhanced proliferation by 80%, dorsal root ganglion by 46%, and spinal cord by 14%. Moreover, neural tissues from rats with nerve injury markedly increased the lymphocyte proliferation compared to coculture with tissues from corresponding normal rats. Schwann cell apoptosis was triggered in vitro when cocultured with lymphocytes from neuropathic rats. CONCLUSION: Our study suggests that chronic neuropathic pain might be caused by chronic inflammation resulting from a nervous autoimmune reaction triggered by nerve injury.

Neutrophil : lymphocyte ratio is associated with disease severity and mortality in patients with Stevens-Johnson syndrome/toxic epidermal necrolysis.

The neutrophil : lymphocyte ratio (NLR), platelet : lymphocyte ratio (PLR), C-reactive protein : albumin ratio (CAR), and albumin : fibrinogen ratio (AFR) have been considered as useful inflammatory biomarkers. However, their roles in Stevens-Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) still remain unclear. This study aimed to test whether NLR, PLR, CAR, and AFR serve as predictive markers of disease severity and systemic inflammation in patients with SJS/TEN. This retrospective study included 40 patients with SJS/TEN and 60 healthy controls. The correlation between these markers and severity-of-illness score for toxic epidermal necrolysis (SCORTEN), ABCD-10, procalcitonin (PCT), C-reactive protein (CRP) were analyzed and compared. Univariable and multivariable analysis were used to assess associations of variables with mortality. The receiver-operator curves (ROC) were used to evaluate the predictive value of variables for mortality in SJS/TEN patients. The results demonstrated that the NLR and PLR of SJS/TEN patients were significantly higher and the AFR was significantly lower when compared with healthy controls (p < 0.05). The NLR and CAR were positively correlated with SCORTEN, ABCD-10, PCT, and CRP. The NLR in SCORTEN of ≥3 group was significantly higher than that in SCORTEN <3 group (p < 0.05) and there were no significant differences between PLR, CAR, and AFR between the two groups. The univariate analysis suggested that NLR of >5.79 was a risk factor for mortality (odds ratio, 10.5; p < 0.05), but the association was no longer statistically significant in multivariable analysis. The ROC showed that NLR had a sensitivity of 85.7% and specificity of 63.6% for predicting death with a cut-off value of 5.79 (p < 0.05) in SJS/TEN patients. In conclusion, among the four markers, NLR and CAR can partially reflect severity and inflammatory status in patients with SJS/TEN. NLR was also a predictor of death.

Propofol pretreatment attenuates aquaporin-4 over-expression and alleviates cerebral edema after transient focal brain ischemia reperfusion in rats.

BACKGROUND: Cerebral edema is a major threat for stroke victims. Most studies have focused on the neuroprotective activities of propofol, addressing infarct volume rather than cerebral edema. Aquaporin-4 (AQP4) plays an important role in maintaining brain water homeostasis under various neurological insults. We explored the effect of propofol pretreatment on cerebral edema in a rat model of brain ischemia reperfusion and assessed the involvement of AQP4. METHODS: To induce brain ischemia reperfusion, we introduced a silicone-coated monofilament nylon suture into the origin of the middle cerebral artery, withdrawing it after 90 min. Treatment groups (n = 32), received propofol (0.1 mL x kg(-1) x min(-1)) infusion for 30 min before occlusion; the vehicle group (n = 32) and the sham-operated group (n = 28), which received the intralipid vehicle at the same time and rate. To assess cerebral infarct volume, we used 2, 3, 5-triphenyl-tetrazolium chloride staining; wet-dry weight ratio was the basis for cerebral edema estimation, and we used immunohistochemistry and Western blot to detect AQP4 expression. RESULTS: The wet-dry weight ratio decreased from 86.89% +/- 0.71% in the vehicle group (n = 6) to 72.42% +/- 0.74% in the propofol group (n = 6), corresponding to an average decrease of 16%. In parallel and based on immunohistochemical semi-quantification, the propofol group exhibited remarkable attenuation of AQP4 over-expression in the ischemic border zone compared with the vehicle group: 1.28 +/- 0.03 vs 1.40 +/- 0.05, n = 7, respectively; P < 0.05. Values derived from Western blot quantification were similarly decreased in the propofol group compared to the vehicle group: 20.85% +/- 4.18% vs 31.67% +/- 3.23%, n = 4, respectively; P < 0.05. However, infarct volume and neurologic deficit in postischemic rats in the propofol group were not statistically different from values in the vehicle group. CONCLUSIONS: We conclude that prestroke treatment with propofol reduces postischemic cerebral edema in rats, possibly through inhibiting AQP4 over-expression in the boundary zone of ischemia.

Effects of the combination of mask preconditioning with midazolam pretreatment on anxiety and mask acceptance during pediatric inhalational induction and postoperative mask fear in children.

BACKGROUND: Anxiety and fear frequently causes an aversion to applying a face mask and increases difficulty during pediatric induction. There is at present little study of this problem. Therefore, the aim of this study was to investigate the effect of the combination of mask preconditioning and midazolam pretreatment on mask acceptance during pediatric induction and on postoperative mask fear. METHODS: One hundred and sixty children were randomly assigned into four groups: the mask preconditioning group (MaG), the midazolam pretreatment group (MiG), the mask/midazolam combination group (Ma/MiG), and the saline group (SaG). The Modified Yale Preoperative Anxiety Scale (m-YPAS) was employed to assess the anxiety in the operation room (OR). A Mask Acceptance Score (MAS) was measured during inhalational induction and the incidence of mask fear (MAS ≤ 2) was evaluated postoperatively. RESULTS: The MaG and Ma/MiG groups had the highest mask acceptance scores but there were no differences between these two groups (P < 0.05). The average anxiety level of children entering the OR was much lower in the MaG and Ma/MiG groups than in the SaG group (P < 0.05). During induction, the anxiety level increased in the SaG and MaG groups but decreased in the MiG and Ma/MiG groups (P < 0.05). At the postoperative third day, the incidence of mask fears was as high as 23% in the SaG group, 15% in the MiG group, but only 2.5% in the MaG and Ma/MiG groups. CONCLUSIONS: The single use of mask preconditioning has a better influence than midazolam for increasing mask acceptance during inhalational induction and reducing postoperative mask fear, reducing the anxiety level during induction, improving induction compliance and shortening the total mask time. A mask preconditioning and midazolam combination did not increase mask acceptance during inhalational induction, reduce mask fears postoperatively, improve induction compliance, nor shorten the total mask time. But it can better reduce the anxiety level during induction.