Pain sensitivity: a feasible way to predict the intensity of stress reaction caused by endotracheal intubation and skin incision?

PURPOSE: Recent studies have shown that pain sensitivity has a significant relationship with clinical pain and may also predict the intensity of pain and analgesic consumption after surgery. However, the correlation between pre-operative pain sensitivity and stress response during anesthesia has not been investigated. Therefore, we aimed to explore the relationship between pre-operative pain sensitivity and stress responses during intubation and skin incision in this study. METHODS: Fifty women (ASA I-II) aged 20-55 years, undergoing elective abdominal surgery requiring at least a 10-cm-long skin incision were studied. Pain sensitivity, including pain threshold and pain tolerance was measured before surgery. In this study, experimental pain was induced by potassium ion conducted via continuous current. When patients reported feeling pain or acted to stop pain, the intensity of the current was recorded to register pain threshold and pain tolerance. The State-Trait Anxiety Inventory (STAI) was used to examine the pre-operative mental status. General anesthesia was induced with intravenous fentanyl and a target-controlled infusion of propofol. Blood samples for norepinephrine (NE) detection were collected at 10 min after entering the operating theater, immediately before intubation, 2 min after intubation, immediately before skin incision and 2 min after incision. Mean arterial blood pressure (MAP) and heart rate (HR) were recorded at the same time. Pearson's correlation test (SPSS 13.0) was then used to analyze the relationship between pain sensitivity and the changes in MAP, HR and NE level. RESULTS: A total of fifty women were enrolled in the study. Their pre-operative pain threshold and pain tolerance were 0.90 ± 0.40 mA and 2.53 ± 0.77 mA,respectively. Changes in MAP, HR and NE before and after intubation or skin incision were significantly related with pre-operative pain tolerance (P < 0.05); however, pain threshold was not correlated with changes in MAP, HR and NE (P > 0.05). The STAI score did not correlate with the stress response either (P > 0.05). CONCLUSIONS: Pain tolerance had a significant relationship with stress response during intubation and skin incision. We may initially use pain tolerance to direct opioid usage in the future.

Dexmedetomidine alleviates anxiety-like behaviors in female mice with musculoskeletal pain through SIRT1/p53 axis.

BACKGROUND: Musculoskeletal pain is the most common form of chronic pain. Anxiety increases pain intensity and appears to have a major impact on the prevalence and also disability of musculoskeletal pain in women. We examined the effect of dexmedetomidine (DEX) on anxiety-like behaviors associated with musculoskeletal pain and the underlying molecular mechanism in female mice. METHODS: Musculoskeletal pain was induced by injection of acidified saline into the gastrocnemius muscle in adult female mice, and the von Frey filament test is used to measure mechanical sensitivity. DEX and EX527 (SIRT1 inhibitor) were administered after modelling. Behavioral tests were used for anxiety and motor activity tests. SIRT1, p53 and acetyl-p53 were quantified by Western blot. RESULTS: Adult female mice with musculoskeletal pain exhibit increased fear-like behavior by reducing SIRT1 expression in the medial prefrontal cortex (mPFC). While administration of DEX was able to alleviate mechanical hypersensitivity and anxiety-like behaviors by blocking SIRT1 decline and acetyl-p53 upregulation in mPFC, EX527 inhibited acetyl-p53 rise and reversed the antinociceptive and anxiolytic effects of DEX. CONCLUSION: DEX may alleviate anxiety-like behaviors in mice with musculoskeletal pain via the SIRT1/p53 axis. These results suggest that DEX may have a potential therapeutic role in musculoskeletal pain-induced anxiety.

Alanyl­glutamine prophylactically protects against lipopolysaccharide­induced acute lung injury by enhancing the expression of HSP70.

At present, the timing of glutamine administration remains controversial. The aim of the present study was to confirm the early protective mechanisms of alanyl­glutamine (Ala­Gln) against lipopolysaccharide (LPS)­induced lung injury, as well as to detect the best time for Ala­Gln usage. A total of 60 adult Wistar rats were randomly divided into 6 groups: The control group (C), the LPS­induced shock group (LPS), the pre­Ala­Gln treated group (A1) and the pre­Gln treated group (G1), which separately received 4.5% Dipeptiven and 3% glutamine just before LPS administration; the post­Ala­Gln treated group (A2) and the post­Gln treated group (G2), which was respectively infused with 4.5% Dipeptiven and 3% glutamine at 1 h following LPS. Survival rates were observed at 6 h following the LPS injection. Blood samples were drawn for analysis of cytokine levels 1 h prior to (T0) and 6 h following (T1) LPS injection. All rats were killed at T1 and the pulmonary samples were collected. Plasma concentrations of tumor necrosis factor­α, interleukin (IL)­1ß and IL­8 at T0 and T1, apoptosis in lung epithelial cells and the expression of heat shock protein (HSP)70 were detected. The lung wet/dry weight ratio (W/D) and the content of protein in the bronchoalveolar lavage fluid (BALF) were also determined. Survival rates at 6 h following (T1) LPS administration were both 100% in groups A1 and G2, but 70% in A2 and G2 groups. The W/D, the content of protein in BALF and cytokine levels were significantly lower in groups A1 and G1 than that in group LPS (P<0.05) at T1. The apoptosis index of both alveolar and bronchial epithelial cells was obviously lower in A1 and G1 groups than that in the LPS group (P<0.05). Gray gradients of HSP70 in the A1 and G1 groups were dramatically higher than those of group LPS (P<0.05). In conclusion, pre­administration of Ala­Gln just before LPS can effectively protect the lung by enhancing HSP70 expression, but delayed administration cannot protect LPS­induced lung injury.

Effect of ulinastatin on the expression and distribution of high mobility group box 1 in human colon carcinoma cells in vitro.

The aim of the present study was to investigate the in vitro effects of ulinastatin (UTI) on the proliferation, invasion, apoptosis, expression and distribution of high mobility group box 1 (HMGB1) and the expression of nuclear factor κB (NF­κB) in human colon carcinoma LoVo cells. The cells were divided into control (untreated), UTI1 (400 U/ml UTI), UTI2 (800 U/ml UTI) and UTI3 (1,600 U/ml UTI) groups. The cell proliferation, invasion, apoptosis and the gene and protein expression of HMGB1 and NF­κB were detected using a tetrazolium assay, Transwell cell invasion assays, a caspase­3 activity assay, western blot analysis and reverse transcription quantitative polymerase chain reaction, respectively. The distribution of HMGB1 was detected using immunofluorescence. LoVo cell proilferation decreased the most in the UTI3 group followed, in order, by the UTI2, UTI1 and control groups. UTI inhibited invasion in LoVo cells and the inhibitory effect was enhanced as the UTI concentration increased. The activity of caspase­3 increased the least in the control group followed, in order, by the UTI1, UTI2 and UTI3 groups. UTI inhibited the expression of HMGB1 and NF­κB, and decreased the cytoplasmic distribution of HMGB1. Thus, UTI inhibited LoVo cell proliferation and induced LoVo cell apoptosis, the mechanism of which may be associated with a decreased in the expression of HMGB1 and NF­κB, and the cytoplasmic distribution of HMGB1.