Objective To compare the success rate and stability of rat models of comorbid chronic pain and depression induced by different doses of complete Freund's adjuvant(CFA).Methods Sixty SD rats were divided randomly into a control group,low-dose CFA group(CFA-L),and high-dose CFA group(CFA-H)(n=20 rats per group).Rats in the CFA-L and CFA-H groups were injected with 50 and 100 μL CFA,respectively,and rats in the control group were injected with 0.9％sodium chloride solution.The general state,body weight,mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were observed at 0,7,14,21,and 28 days after modeling.Depressive behavior was evaluated using the open field test(OFT),forced swim test(FST),and tail suspension test(TST).Glutamate(Glu)and γ-aminobutyric acid(GABA)levels in the anterior cingulate cortex were detected by enzyme-linked immunosorbent assay.Brain-derived neurotrophic factor(BDNF)expression in the anterior cingulate cortex was detected by immunohistochemistry,and pathological changes in the anterior cingulate cortex were observed by HE staining.Results(1)Regarding the general condition of the rats,the left ankle joint and toes were obviously red and swollen in the CFA-L and CFA-H groups on the 7th day after modeling,and the swelling was more severe in the CFA-H group.The redness and swelling of the left hind foot and ankle joint and toes gradually recovered in the CFA-L group on days 14,21,and 28 after modeling,but were still obvious in the CFA-H group,and the water and food intake decreased.(2)The body mass was significantly lower in rats in the CFA-H group compared with those in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05).(3)Regarding pain-related behavior,the MWT and TWL were significantly decreased in the CFA-L and CFA-H groups on the 7th and 14th days after modeling,compared with the control group(P＜0.05,P＜0.05).On day 21 after modeling,MWT was significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),and TWL was significantly lower in the CFA-L and CFA-H groups than in the blank group(P＜0.05,P＜0.05).On day 28 after modeling,MWT and TWL were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05).(4)In terms of depression-related behaviors,the total OFT movement distance was significantly lower in the CFA-H group than in the blank and CFA-L groups on day 7 after modeling(P＜0.05,P＜0.05).The total OFT distance and central dwell time were significantly lower in the CFA-H group than in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05),and the result in the FST and TST were significantly higher than in the blank and CFA-L groups(P＜0.05,P＜0.05).(5)Glu,GABA,and BDNF expression levels were significantly higher in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),while GABA,Glu/GABA,and BDNF levels were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05,P＜0.05).(6)The CFA-L group showed less damage in the anterior cingulate cortex,more pyramidal cells,more arranged cells,clear nucleoli,and a small number of cells with karyokynesis and deep staining.Compared with the CFA-L group,rats in the CFA-H group showed a disordered cell arrangement in the injured area of the anterior cingulate cortex,a large number of pyknotic and hyperchromatic neurons,significantly fewer or absent pyramidal cells,and vacuoles,red blood cells,and neurofibrillary tangles in the interstitial space.Conclusions Injection of CFA 100 μL can be used to establish a rat model of chronic inflammatory pain and depression,showing hyperalgesia,depression-like behavioral changes,changes in levels of Glu,GABA,and BDNF in the anterior cingulate cortex,and pathological changes in the anterior cingulate cortex,consistent with the pathophysiological characteristics of chronic pain and depression.

Objective To compare the success rate and stability of rat models of comorbid chronic pain and depression induced by different doses of complete Freund's adjuvant(CFA).Methods Sixty SD rats were divided randomly into a control group,low-dose CFA group(CFA-L),and high-dose CFA group(CFA-H)(n=20 rats per group).Rats in the CFA-L and CFA-H groups were injected with 50 and 100 μL CFA,respectively,and rats in the control group were injected with 0.9％sodium chloride solution.The general state,body weight,mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were observed at 0,7,14,21,and 28 days after modeling.Depressive behavior was evaluated using the open field test(OFT),forced swim test(FST),and tail suspension test(TST).Glutamate(Glu)and γ-aminobutyric acid(GABA)levels in the anterior cingulate cortex were detected by enzyme-linked immunosorbent assay.Brain-derived neurotrophic factor(BDNF)expression in the anterior cingulate cortex was detected by immunohistochemistry,and pathological changes in the anterior cingulate cortex were observed by HE staining.Results(1)Regarding the general condition of the rats,the left ankle joint and toes were obviously red and swollen in the CFA-L and CFA-H groups on the 7th day after modeling,and the swelling was more severe in the CFA-H group.The redness and swelling of the left hind foot and ankle joint and toes gradually recovered in the CFA-L group on days 14,21,and 28 after modeling,but were still obvious in the CFA-H group,and the water and food intake decreased.(2)The body mass was significantly lower in rats in the CFA-H group compared with those in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05).(3)Regarding pain-related behavior,the MWT and TWL were significantly decreased in the CFA-L and CFA-H groups on the 7th and 14th days after modeling,compared with the control group(P＜0.05,P＜0.05).On day 21 after modeling,MWT was significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),and TWL was significantly lower in the CFA-L and CFA-H groups than in the blank group(P＜0.05,P＜0.05).On day 28 after modeling,MWT and TWL were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05).(4)In terms of depression-related behaviors,the total OFT movement distance was significantly lower in the CFA-H group than in the blank and CFA-L groups on day 7 after modeling(P＜0.05,P＜0.05).The total OFT distance and central dwell time were significantly lower in the CFA-H group than in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05),and the result in the FST and TST were significantly higher than in the blank and CFA-L groups(P＜0.05,P＜0.05).(5)Glu,GABA,and BDNF expression levels were significantly higher in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),while GABA,Glu/GABA,and BDNF levels were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05,P＜0.05).(6)The CFA-L group showed less damage in the anterior cingulate cortex,more pyramidal cells,more arranged cells,clear nucleoli,and a small number of cells with karyokynesis and deep staining.Compared with the CFA-L group,rats in the CFA-H group showed a disordered cell arrangement in the injured area of the anterior cingulate cortex,a large number of pyknotic and hyperchromatic neurons,significantly fewer or absent pyramidal cells,and vacuoles,red blood cells,and neurofibrillary tangles in the interstitial space.Conclusions Injection of CFA 100 μL can be used to establish a rat model of chronic inflammatory pain and depression,showing hyperalgesia,depression-like behavioral changes,changes in levels of Glu,GABA,and BDNF in the anterior cingulate cortex,and pathological changes in the anterior cingulate cortex,consistent with the pathophysiological characteristics of chronic pain and depression.

Acupuncture treatment of chronic pain combined with depression (CPDC) is the result of a multi-target, multi-pathway approach. Acupuncture can treat CPDC by inhibiting the activation of glial cells, regulating the release of inflammatory mediators, regulating the expressions of neurotransmitters, changing the plasticity of neural synapses, regulating related epigenetic effects, regulating the microbiota-brain-gut axis, inhibiting nerve cell apoptosis, and antagonizing oxidative stress. The mechanism of its effect mainly involves anti-inflammatory related signaling pathways, regulation of neural synapse-related signaling pathways, and exerts its therapeutic effect through hippocampus, cerebral cortex, and amygdala.

Objective:To observe the protective effect of Angong Niuhuang pill on brain function of rats with sepsis, explore its protective mechanism, and provide the experimental basis for clinical application of Angong Niuhuang pill in the treatment of sepsis-associated encephalopathy (SAE).Methods:Thirty male Sprague-Dawley (SD) rats were divided into sham operation group, sepsis model group and Angong Niuhuang pill group according to random number table method, with 10 rats in each group. The sepsis model was established by cecal ligation and puncture (CLP); rats in sham operation group received open and closed abdomen. The rats in the Angong Niuhuang pill group were given Angong Niuhuang pill (0.3 g/kg) by gastric irrigation daily for 3 days before CLP, and the drugs were administrated 12 hours after modeling again. After 24 hours of CLP, the neuroreflex scores were evaluated, white blood cell count (WBC), the levels of serum neuron-specific enolase (NSE) and S100β were detected. Then the brain tissue was harvested. After hematoxylin-eosin (HE) staining, the pathological changes of brain tissue were observed under the light microscope. The mRNA expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in brain tissue were detected by polymerase chain reaction.Results:Compared with the sham operation group, the total score of neuroreflex scores in the sepsis model group and the Angong Niuhuang pill group were significantly reduced (4.43±1.40, 6.57±1.90 vs. 9.40±0.84, both P < 0.05), WBC, serum NSE, S100β were significantly increased [WBC (×10 9/L): 8.07±1.32, 5.84±0.94 vs. 3.60±0.32; NSE (μg/L): 1.04±0.14, 0.61±0.07 vs. 0.16±0.04; S100β (ng/L): 255.624±30.25, 97.72±15.41 vs. 46.88±12.03, all P < 0.05], and the mRNA expressions of IL-6 and TNF-α in brain tissue were significantly increased [IL-6 mRNA (2 -ΔΔCt): 5.668±2.195, 3.605±1.014 vs. 0.997±0.329; TNF-α mRNA (2 -ΔΔCt): 18.996±0.913, 1.746±0.710 vs. 0.674±0.132, all P < 0.05]. Compared with the sepsis model group, the total score of neuroreflex scores in the Angong Niuhuang pill group was significantly increased (6.57±1.90 vs. 4.43±1.40, P < 0.05), WBC, serum NSE, S100β concentration, and the mRNA expressions of IL-6 and TNF-α in the brain were significantly reduced [WBC (×10 9/L): 5.84±0.94 vs. 8.07±1.32, NSE (μg/L): 0.61±0.07 vs. 1.04±0.14, S100β (ng/L): 97.72±15.41 vs. 255.62±30.25, IL-6 mRNA (2 -ΔΔCt): 3.605±1.014 vs. 5.668±2.195, TNF-α mRNA (2 -ΔΔCt): 1.746±0.710 vs. 18.996±0.913, all P < 0.05]. Brain histopathological observation showed that the hippocampal neurons in the sepsis model group were disordered arrangement, a large number of neuronal nuclei were contracted, and the tissue was loose with obvious edema. Compared with the sepsis model group, the Angong Niuhuang pill group had less nuclear shrinkage and tissue edema. Conclusions:The pretreatment of the Angong Niuhuang pill can improve the brain dysfunction of septic rats and reduce the expression of pro-inflammatory cytokines in the brain. It is speculated that the Angong Niuhuang pill can protect the brain function in sepsis by inhibiting the inflammatory reaction in the brain.

Objective To evaluate the use of nasojejunal tube in early enteral nutrition in severe traumatic brain injury (STBI) patients under mechanical ventilation.Methods STBI patients requiring mechanical ventilation in intensive care unit (ICU) of the First Affiliated Hospital of Bengbu Medical College admitted in 2013 were randomly divided into the jejunal tube group (n =15) and gastric tube group (n =19).We compared the 2 groups in terms of the tolerable beginning time of enteral nutrition (EN),the time before reaching target feeding volume,the incidences of gastrointestinal complications and ventilator-associated pneumonia (VAP) during EN,mechanical ventilation time,ICU hospital stay,and 28-day mortality rate.Results The tolerable beginning time of EN [(51.73 ± 9.16) hours vs.(81.11 ± 11.82) hours,t =7.920,P ＜0.05] and the time required to reach target feeding volume [(87.27 ± 9.99) hours vs.(152.05 ± 28.74) hours,t =8.320,P ＜ 0.05] in the jejunal tube group were significantly shorter than those in the gastric tube group.In the process of EN,compared with the gastric tube group,the incidences of gastric retention (6.7％ vs.57.9％,x2 =10.937,P ＜ 0.05),reflux (0％ vs.36.8％,x2 =9.566,P ＜ 0.05),vomiting (20.0％.vs.63.2％,x2 =6.642,P＜0.05),aspiration (6.7％ vs.42.1％,x2 =6.087,P＜0.05),VAP (33.3％ vs.73.7％,x2 =5.536,P ＜ 0.05) in the jejunum tube group were significantly lower.The mechanical ventilation time [(10.73 ± 4.68) days vs.(15.74 ± 2.54) days,t =3.730,P＜0.05] and the ICU hospital stay [(13.60 ± 4.80) days vs.(17.42 ± 4.05) days,t =2.497,P ＜0.05] of the jejunum tube group were significantly shorter than those of the gastric tube group.Comparison of 28-day mortality rate between the two groups revealed no statistically significant difference.Conclusion Early implementation of EN via nasojejunal tube in mechanically ventilated STBI patients can alleviate feeding intolerance,shorten the beginning time of EN and the time required to reach target feeding volume,reduce the incidence of complications,and shorten mechanical ventilation time and hospital stay in ICU.