仲景原文“烦疼”“疼烦”症考释

[目的]考证《伤寒论》《金匮要略》中“烦疼”“疼烦”的含义。[方法]从历代注家注疏入手,对不同观点进行归纳、分析,同时通过文字学考证,参考秦汉医学与非医文献,探明“烦”字字义,并结合张仲景原文分析二症含义。[结果]历代注家将二症释为疼痛剧烈、疼痛并烦扰、热疼不妥。文字学考证可见,“烦”字除了表示心神的不适感之外,还有繁多、频繁之意。在张仲景原文中二症与具体身体部位连用,见于湿病、疟病、少阳病等,表示疼痛频繁、反复。[结论]张仲景原文中“烦疼”“疼烦”实为“疼痛频繁”之意。

自拟牙痛定疼汤治疗牙髓炎牙痛临床疗效及对复发的影响

目的探讨自拟牙痛定疼汤治疗牙髓炎牙痛临床疗效及对复发的影响。方法择取杭州市萧山区中医院2018年5月—2021年6月期间收治的160例牙髓炎患者为研究对象,将其按照随机数遍法分为对照组(78例)和观察组(82例),对照组给予常规治疗,观察组在上述基础实施拟牙痛定疼汤治疗,连续治疗2周,比较两组患者临床疗效,以及治疗前后疼痛程度、龈沟液细胞因子[白细胞介素-1β(IL-1β)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、肝细胞生长因子(HGF)],统计复发情况。结果观察组临床有效率(91.46%,75/82)较对照组(74.36%,58/78)显著升高,且差异有统计学意义(P<0.05);治疗前,两组患者疼痛视觉模拟评分量表(VAS)评分、龈沟液细胞因子(IL-1β、IL-8、TNF-α、HGF)水平比较无统计学意义(P>0.05),治疗后,两组患者上述指标均下降,且观察组较对照组更低(P<0.05);观察组复发率(8.54%,7/82)较对照组(25.64%,20/78)明显低(P<0.05);观察组不良反应发生率(6.10%,5/82)略高于对照组(3.84%,3/78),差异无统计学意义(P>0.05)。结论自拟牙痛定疼汤治疗牙髓炎牙痛临床疗效佳,可有效缓解疼痛,下调龈沟液炎症因子表达及HGF浓度,复发率低,且安全性良好。

疼不疼

小林牙疼，爸爸带他到医院拔牙。经过惊心动魄的拔牙过程后，小林终于可以和爸爸回家了。

据出土文献说“痛心疾首”及相关字词

成语{痛心疾首}由{痛心}和{疾首}两个词组合而成。卜辞中“疾首”与“首疾”并见。“疾”字在商代甲骨文中就已出现,“病”字则是到了战国时代才出现。在战国出土文献中,“疾”表示的病情比“病”更严重,与《说文解字》的记载相反。{疾}{病}都是非宾格动词,故在“N1+V+N2”这种句式中,可移位为“N1+N2+V”,且N1和N2有领属关系。{痛}{疼}则是典型的不及物动词,不能带宾语,因此{痛心}{疼心}不符合语法规则。“痛心”“疼心”原本作“疾心”。{疾首}和{疾心}本指生理上的疼痛不适感,在春秋末期引申指精神上的痛苦或痛恨,为了强调一种极度的痛苦痛恨而组合成一个四字成语,为了避复,将{疾心}改成{痛心},从而组成{痛心疾首}这个成语。{痛心}一词在汉代以后才开始流行,当是从成语{痛心疾首}中分割出来的。

Genetic Evidence for Causal Association Between Hypertension and Chronic Pain:A Bidirectional Two-Sample Mendelian Randomization Study

Objective The extent to which the association between hypertension and chronic pain in observational studies is either causally linked or influenced by other shared risk factors has not been substantially addressed.In the present study,Mendelian randomization(MR)was employed to examine the potential causal relationship between hypertension and risk of chronic pain.Methods The study data were derived from the pooled dataset of the genome-wide association study(GWAS),enabling the evaluation of the causal effects of hypertension on various types of chronic pain including chronic headache as well as chest,abdominal,joint,back,limb,and multisite chronic pain.We performed a bidirectional two-sample MR analysis using random effect inverse variance weighting(IVW),MR-Egger,weighted median,and weighted mode,quantified by odds ratio(OR).Results Genetically predicted essential hypertension was associated with an increased risk of chronic headache(OR=1.007,95%CI:1.003-1.011,P=0.002)and limb pain(OR=1.219,95%CI:1.033-1.439,P=0.019).No potential causal associations were identified between chronic pain and essential hypertension in the reverse direction MR(P>0.05).In addition,there was no potential causal association between secondary hypertension and chronic pain(P>0.05).Conclusion This study provided genetic evidence that a unidirectional causal relationship exists between essential hypertension and the increased risks of chronic headache and limb pain,and no causal relationship was found between secondary hypertension and chronic pain.These findings offer theoretical underpinnings for future research on managing hypertension and chronic pain.

RANDOMIZED CONTROL STUDY ON DEPRESSION INDUCED BY CHRONIC PAIN TREATED WITH ACUPUNCTURE

Objective To study and verify the efficacy of acupuncture on depression caused by chronic pain and to further analyze the advantages of acupuncture. Methods According to random number table, the cases were randomized into experimental group and western medicine group, treated with acupuncture and antidepression drug （deanxit） respectively. Hamilton Depressive Scale （HAMD） and Visual Analogue Scale （VAS） were adopted for the evaluation before treatment and in the 1, 2 and 4 weeks after treatment in two groups successively. Results ① Very significant differences had been achieved on the comparisons of HAMD, VAS and HAMD reducing rate before and after treatment in experimental group （P 〈 0.01）. Very significant differences had been achieved in the comparisons of HAMD, VAS and HAMD reducing rate before and after treatment in western medicine group （P 〈 0.01 ）. ③Significant differences in HAMD reducing rate^＊ and VAS score^＊ ＊ had been achieved in the comparison between experiment group and western medicine group 1 week after treatment （^＊ P〈0.01, ^＊ ＊ P〈0.05）. ④ The significant differences had not been received in HAMD, VAS score and HAMD reducing rate in 2 and 4 weeks after treatment in the comparison between experimental group and western medicine group （P 〉0.05）. ⑤ No any harmful effect happened in experimental group after treatment, but it happened in western medicine group. Conclusion Both acupuncture and deanxit have achieved the definite therapeutic effects on depression caused by chronic pain, with similar efficacy. But the effects of acupuncture are obtained more quickly. In comparison of western medicine, acupuncture has no side and harmful effect. Additionally, acupuncture applies the multi-targeting and holistic modulation to the whole body.

Limited water infusion decreases pain during minimally sedated colonoscopy

AIM:To investigate a limited water infusion method in colonoscopy.METHODS:Consecutive patients undergoing minimally sedated colonoscopy were randomized to receive air insufflation(n = 89) or water infusion limited to the rectum,sigmoid colon and descending colon(n = 90).Completion rates,cecal intubation times,procedure times,need for abdominal compression,turning of patients and levels of discomfort were evaluated.RESULTS:Completion rates,total procedure times,need for abdominal compression,and turning of patients were similar between groups.Less pain was experienced in the water group than in the air group(2.5 ± 2.5 vs 3.4 ± 2.8,mean ± SD,P = 0.021).The cecal intubation time was significantly longer in the water group than in the air group(6.4 ± 3.1 min vs 4.5 ± 2.4 min,P < 0.001).More water was infused in the water group(322 ± 80.9 mL vs 26.2 ± 39.4 mL,P < 0.001).CONCLUSION:Limited airless water infusion in the distal colon reduces patients' pain during colonoscopy.

Therapeutic effects of Caspase-1 inhibitors on acute lung injury in experimental severe acute pancreatitis

AIM： To assess the therapeutic effect of Caspase-1 inhibitors （ICE-I） on acute lung injury （ALI） in experimental severe acute pancreatitis （SAP）. METHODS： Forty-two SD rats were randomly divided into 3 groups： healthy controls （HC, n = 6）; SAP-S group （n = 18）; SAP-ICE-i group （n = 18）. SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. HC rats underwent the same surgical procedures and duct cannulation without sodium taurocholate infusion, in SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis and a repeated injection after 12 h. In SAP-ICE-I group, the rats were firstly given ICE inhibitors intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, the injection was repeated at 12 h. Serum 1L-1β was measured by EUSA. Intrapulmonary expression of Caspase-1, IL-1β and IL-18 mRNA were detected by semi-quantitative RT-PCR. The wet/dry weight ratios and histopathological changes of the lungs were also evaluated. RESULTS： Serum IL-1β levels in SAP-S group were 276.77 ± 44.92 pg/mL at 6 h, 308.99 ± 34.95 pg/mL at 12 h, and 311.60 ± 46.51 pg/mL at 18 h, which were increased significantly （P 〈 0.01, vs HC）. in SAP- ICE-I group, those values were decreased significantly （P 〈 0.01, vs SAP-S）. intrapulmonary expression of Caspase-1, IL-1β and IL-18 mRNA were observed in the HC group, while they were increased significantly in the SAP-S group （P 〈 0.01, vs HC）. The expression of IL-lβ and IL-18 mRNA were decreased significantly in the SAP- ICE-I group （P 〈 0.01, vs SAP-S）, whereas Caspase-1 mRNA expression had no significant difference （P 〉 0.05）. The wet/dry weight ratios of the lungs in the SAP-S group were increased significantly （P 〈 0.05 at 6 h, P 〈 0.01 at 12 h and 18 h, vs HC） and they were decreased significantly in the SAP-ICE-I group （P 〈 0.05, vs SAP-S）.Caspase-1 inhibitors ameliorated the severity of ALl in SAP.CONCLUSION： Caspase-1 activation, and overproduction of IL-1β and IL-18 play an important role in the course of ALI, and Caspase-1 inhibition is effective for the treatment of ALI in experimental SAP.

Characterization of functional biliary pain and dyspeptic symptoms in patients with sphincter of Oddi dysfunction:Effect of papillotomy

AIM： To characterize functional biliary pain and other gastrointestinal （GI） symptoms in postcholecystectomy syndrome （PCS） patients with and without sphincter of Oddi dysfunction （SOD） proved by endoscopic sphincter of Oddi manometry （ESOM）, and to assess the postendoscopic sphincterotomy （EST） outcome. METHODS： We prospectively investigated 85 cholecystectomized patients referred for ERCP because of PCS and suspected SOD. On admission, all patients completed our questionnaire. Physical examination, laboratory tests, abdominal ultrasound, quantitative hepatobiliary scintigraphy （QHBS）, and ERCP were performed in all patients. Based on clinical and ERCP findings 15 patients had unexpected bile duct stone disease and 15 patients had SOD biliary type Ⅰ. ESOM demonstrated an elevated basal pressure in 25 patients with SOD biliary-type Ⅲ. In the remaining 30 cholecystectomized patients without SOD, the liver function tests, ERCP, QHBS and ESOM were all normal. As a control group, 30 ‘asymptomatic＇ cholecystectomized volunteers （attended to our hospital for general cardiovascular screening） completed our questionnaire, which is consisted of 50 separate questions on GI symptoms and abdominal pain characteristics. Severity of the abdominal pain （frequency and intensity） was assessed with a visual analogue scale （VAS）. In 40 of 80 patients having definite SOD （i.e. patients with SOD biliary type Ⅰ and those with elevated SO basal pressure on ESOM）, an EST was performed just afl：er ERCP. In these patients repeated questionnaires were filled at each follow-up visit （at 3 and 6 too） and a second look QHBS was performed 3 mo after the EST to assess the functional response to EST. RESULTS： The analysis of characteristics of the abdominal pain demonstrated that patients with common bile duct stone and definite SOD had a significantly higher score of symptomatic agreement with previously determined biliary-like pain features than patient groups of PCS without SOD and controls. In contrary, no significant differences were found when the pain severity scores were compared in different groups of PCS patients. In patients with definite SOD, EST induced a significant acceleration of the transpapillary bile flow; and based on the comparison of VASs obtained from the pre-and post-EST questionnaires, the severity scores of abdominal pain were significantly improved, however, only 15 of 35 （43%） patients became completely pain free. Post-EST severity of abdominal pain by VASs was significantly higher in patients with predominant dyspepsia at initial presentation as compared to those without dyspeptic symptoms. CONCLUSION： Persistent GI symptoms and general patient dissatisfaction is a rather common finding after EST in patients with SOD, and correlated with the presence of predominant dyspeptic symptoms at the initial presentation, but does not depend on the technical and functional success of EST.

Abnormal endogenous pain modulation and somatic and visceral hypersensitivity in female patients with irritable bowel syndrome

AIM： To investigate the role of endogenous pain modulatory mechanisms in the central sensitization implicated by the visceral hypersensitivity demonstrated in patients with irritable bowel syndrome （IBS）. Dysfunction of modulatory mechanisms would be expected to also result in changes of somatic sensory function. METHODS： Endogenous pain modulatory mechanisms were assessed using heterotopic stimulation and somatic and visceral sensory testing in IBS. Pain intensities （visual analogue scale, VAS 0-100） during suprathreshold rectal distension with a barostat, cold pressor stimulation of the foot and during both stimuli simultaneously （heterotopic stimulation） were recorded in 40 female patients with IBS and 20 female healthy controls. RESULTS： Rectal hypersensitivity （defined by 95% Cl of controls） was seen in 21 （53%）, somatic hypersensitivity in 22 （55%） and both rectal and somatic hypersensitivity in 14 of these IBS patients. Heterotopic stimulation decreased rectal pain intensity by 6 （-11 to -1） in controls, but increased rectal pain by 2 （-3 to ＋6） in all IBS patients （P 〈 0.05） and by 8 （-2 to ＋19） in IBS patients with somatic and visceral hypersensitivity （P 〈 0.02）. CONCLUSION： A majority of IBS patients had abnormal endogenous pain modulation and somatic hypersensitivity as evidence of central sensitization.

Health-related quality of life in gastroesophageal reflux patients with noncardiac chest pain: Emphasis on the role of psychological distress

AIM To investigate the effects of depression and anxiety on health-related quality of life(QoL)in gastroesophageal reflux disease(GERD)patients and those suffering from cardiac(CCP)and noncardiac(NCCP)chest pain in Wuhan,China.METHODS In this cross-sectional study,a total of 358 consecutive patients with GERD were enrolled in Wuhan,China,of which 176 subjects had complaints of chest pain.Those with chest pain underwent coronary angiography and were divided into a CCP group(52 cases)and NCCP group(124 cases).Validated GERD questionnaires were completed,and the 36-item Short-Form Health Survey and Hospital Anxiety/Depression Scale were used for evaluation of Qo L and psychological symptoms,respectively.RESULTS There were similar ratios and levels of depression and anxiety in GERD with NCCP and CCP.However,the QoL was obviously lower in GERD with CCP than NCCP(48.34±17.68 vs 60.21±20.27,P<0.01).In the GERD-NCCP group,rather than the GERD-CCP group,the physical and mental QoL were much poorer in subjects with depression and/or anxiety than those without anxiety or depression.Anxiety and depression had strong negative correlations with both physical and mental health in GERD-NCCP(all P<0.01),but only a weak relationship with mental components of QoL in GERD-CCP.CONCLUSION High levels of anxiety and depression may be more related to the poorer QoL in GERD patients with NCCP than those with CCP.This highlights the importance of evaluation and management of psychological impact for improving QoL in GERD-NCCP patients.

Drainage after total thyroidectomy or lobectomy for benign thyroidal disorders

Objective: This prospective randomized clinical trial was conducted to evaluate the necessity of drainage after total thyroidectomy or lobectomy for benign thyroidal disorders. Methods: A total of 116 patients who underwent total thyroidectomy or lobectomy for benign thyroidal disorders were randomly allocated to be drained or not. Operative and postoperative outcomes including operating time, postoperative pain assessed by visual analogue scale (VAS), total amount of intramuscular analgesic administration, hospital stay, complications, necessity for re-operation and satisfaction of patients were all assessed. Results: The mean operating time was similar between two groups (the drained and non-drained groups). The mean VAS score was found to be significantly low in the non-drained group patients in postoperative day (POD) 0 and POD 1. The mean amount of intramuscular analgesic requirement was significantly less in the non-drained group. One case of hematoma, two cases of seroma and three cases of transient hypoparathyroidism occurred in the non-drained group, whereas one case of hematoma, two cases of seroma, two cases of wound infections and two cases of transient hypoparathyroidism occurred in the drained group. No patient needed re-operation for any complication. The mean hospital stay was significantly shorter and the satisfaction of patients was superior in the non-drained group. Conclusion: These findings suggest that postoperative complications cannot be prevented by using drains after total thyroidectomy or lobectomy for benign thyroid disorders. Furthermore, the use of drains may increase postoperative pain and the analgesic requirement, and prolong the hospital stay. In the light of these findings, the routine use of drains might not be necessary after thyroid surgery for benign disorders.

Evaluation of the biliary tract in patients with functional biliary symptoms

The aim of this paper was to describe functional biliary syndromes and methods for evaluation of the biliary tract in these patients. Functional biliary symptoms can be defined as biliary symptoms without demonstrable organic substrate. Two main syndromes exist： Gallbladder dysfunction and sphincter of Oddi dysfunction. The most important investigative tools are cholescintigraphy and endoscopic sphincter of Oddi manometry. In gallbladder dysfunction a scintigraphic gallbladder ejection fraction below 35% can select patients who will benefit from cholecystectomy. Endoscopic sphincter of Oddi manometry is considered the gold standard in sphincter of Oddi dysfunction but recent development in scintigraphic methods is about to change this. Thus, calculation of hilum-to-duodenum transit time and duodenal appearance time on cholescintigraphy have proven useful in these patients. In conclusion, ambient methods can diagnose functional biliary syndromes. However, there are still a number of issues where further knowledge is needed. Probably the next step forward will be in the area of sensory testing and impedance planimetric methods.

Sphincter of Oddi dysfunction: Managing the patient with chronic biliary pain

Sphincter of Oddi dysfunction （SOD） is a syndrome of chronic biliary pain or recurrent pancreatitis due to functional obstruction of pancreaticobiliary flow at the level of the sphincter of Oddi. The Milwaukee classification stratifies patients according to their clinical picture based on elevated liver enzymes, dilated common bile duct and presence of abdominal pain. Type Ⅰ patients have pain as well as abnormal liver enzymes and a dilated common bile duct. Type Ⅱ SOD consists of pain and only one objective finding, and Type Ⅲ consists of biliary pain only. This classification is useful to guide diagnosis and management of sphincter of Oddi dysfunction. The current gold standard for diagnosis is manometry to detect elevated sphincter pressure, which correlates with outcome to sphincterotomy. However, manometry is not widely available and is an invasive procedure with a risk of pancreatitis. Non-invasive testing methods, including fatty meal ultrasonography and scintigraphy, have shown limited correlation with manometric findings but may be useful in predicting outcome to sphincterotomy. Endoscopic injection of botulinum toxin appears to predict subsequent outcome to sphincterotomy, and could be useful in selection of patients for therapy, especially in the setting where manometry is unavailable.

Pain management in chronic pancreatitis

Abdominal pain is a major clinical problem in patients with chronic pancreatitis. The cause of pain is usually multifactorial with a complex interplay of factors contributing to a varying degree to the pain in an individual patient and, therefore, a rigid standardized approach for pain control tends to lead to suboptimal results. Pain management usually proceeds in a stepwise approach beginning with general lifestyle recommendations. Low fat diet, alcohol and smoking cessation are encouraged. Analgesics alone are needed in almost all patients. Maneuvers aimed at suppression of pancreatic secretion are routinely tried. Patients with ongoing symptoms may be candidates for more invasive options such as endoscopic therapy, and resective or drainage surgery. The role of pain modifying agents (antidepressants, gabapentin, peregabalin), celiac plexus block, antioxidants, octreotide and total pancreatectomy with islet cell auto transplantation remains to be determined.

Ligustrazine alleviates acute renal injury in a rat model of acute necrotizing pancreatitis

AIM: To evaluate the effect of ligustrazine, a traditional Chinese medicine, on renal injury in a rat model of acute necrotizing pancreatitis (ANP). METHODS: A total of 192 rats were randomly divided into three groups: control (C group), ANP without treatment (P group), and ANP treated with ligustrazine (T group). Each group was further divided into 0.5, 2, 6, 12 h subgroups. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Sodium taurocholate was infused through the pancreatic membrane to induce ANP. T group was infused sodium taurocholate as above, and 0.6% ligustrazine was then administered via the femoral vein. Serum urea nitrogen (BUN) and creatinine (Cr) concentrations were measured for the evaluation of renal function. The effects of ligustrazine on the severity of renal injury were assessed by renal function, TXA2/PGI2 and histopathological changes. Renal blood flow was determined by the radioactive microsphere technique (RMT).RESULTS: Compared with control group, the renal blood flow in P group was decreased significantly. Serious renal and pancreatic damages were found in P group, the BUN and Cr levels were elevated significantly, and the ratio of TXA2 to PGI2 was increased at 2, 6 and 12 h. Compared with P group, the blood flow of kidney was elevated significantly at 6 and 12 h after induction of ANP, the renal and pancreatic damages were attenuated, and the BUN and Cr levels were decreased significantly, and the ratio of TXA2 to PGI2 was decreased at 6 and 12 h in T group.CONCLUSION: Microcirculatory disorder (MCD) is an important factor for renal injury in ANP. Ligustrazine can ameliorate the condition of MCD and the damage of pancreas and kidney.

Chronic proctalgia and chronic pelvic pain syndromes:New etiologic insights and treatment options

This systematic review addresses the pathophysiology, diagnostic evaluation, and treatment of several chronic pain syndromes affecting the pelvic organs:chronic proctalgia, coccygodynia, pudendal neuralgia, and chronic pelvic pain. Chronic or recurrent pain in the anal canal, rectum, or other pelvic organs occurs in 7% to 24% of the population and is associated with impaired quality of life and high health care costs. However, these pain syndromes are poorly understood, with little research evidence available to guide their diagnosis and treatment. This situation appears to be changing:A recently published large randomized,controlled trial by our group comparing biofeedback, electrogalvanic stimulation, and massage for the treatment of chronic proctalgia has shown success rates of 85% for biofeedback when patients are selected based on physical examination evidence of tenderness in response to traction on the levator ani muscle-a physical sign suggestive of striated muscle tension. Excessive tension (spasm) in the striated muscles of the pelvic floor appears to be common to most of the pelvic pain syndromes. This suggests the possibility that similar approaches to diagnostic assessment and treatment may improve outcomes in other pelvic pain disorders.

Local anesthesia with ropivacaine for patients undergoing laparoscopic cholecystectomy

AIM:To investigate the effect of pain relief after infu-sion of ropivacaine at port sites at the end of surgery.METHODS:From October 2006 to September 2007,72 patients undergoing laparoscopic cholecystectomy(LC) were randomized into two groups of 36 patients.One group received ropivacaine infusion at the port sites at the end of LC and the other received normal saline.A visual analog scale was used to assess postoperative pain when the patient awakened in the operating room,6 and 24 h after surgery,and before discharge.The amount of analgesics use was also recorded.The demographics,laboratory data,hospital stay,and perioperative complications were compared between the two groups.RESULTS:There was no difference between the two groups preoperatively in terms of demographic and lab-oratory data.After surgery,similar operation time,blood loss,and no postoperative morbidity and mortality were observed in the two groups.However,a significantly lower pain score was observed in the patients undergo-ing LC with local anesthesia infusion at 1 h after LC and at discharge.Regarding analgesic use,the amount of meperidine used 1 h after LC and the total used during admission were lower in patients undergoing LC with local anesthesia infusion.This group also had a shorter hospital stay.CONCLUSION:Local anesthesia with ropivacaine at the port site in LC patients signif icantly decreased post-operative pain immediately.This explains the lower meperidine use and earlier discharge for these patients.

Establishment of model of visceral pain due to colorectal distension and its behavioral assessment in rats

AIM： To establish a visceral pain model via colorectal distension （CRD） and to evaluate the efficiency of behavioral responses of CRD by measuring the score of abdominal withdrawal reflex （AWR） in rats. METHODS： Thirty-eight male SD rats weighing 180-240g were used to establish the visceral pain model. The rat was inserted intra-anally with a 7 cm long flexible latex balloon under ether anesthesia, and colorectal distensions by inflating the balloon with air were made 30 min after recovering from the anesthesia. Five AWR scores （AWR0 to AWR4） were used to assess the intensity of noxious visceral stimuli. It was regarded as the threshold of the minimal pressure （kPa）. For abdominal flatting was induced by colorectal distension. RESULTS： A vigorous AWR to distension of the descending colon and rectum was found in 100% of the awake rats tested. The higher the pressure of distension, the higher the score of AWR. The distension pressures of 0, 2.00, 3.33, 5.33 and 8.00 kPa produced different AWR scores （P〈0.05）. The pain threshold of AWR was constant for up to 80 min after the initial windup （first 1-3 distensions）, the mean threshold was 3.69±0.35 kPa. Systemic administration of morphine sulfate elevated the threshold of visceral pain in a dosedependent and naloxone reversible manner. CONCLUSION： Scoring the AWR during colorectal distensions can assess the intensity of noxious visceral stimulus. Flatting of abdomen （AWR 3） to CRD as the visceral pain threshold is clear, constant and reliable. This pain model and its behavioral assessment are good for research on visceral pain and analgesics.

Moxibustion eases chronic inflammatory visceral pain through regulating MEK, ERK and CREB in rats

AIM To investigate the effects of herb-partitioned moxibustion(HPM) on phosphorylation of mitogen-activated extracellular signal-regulated kinase(MEK)1, extracellular signal-regulated kinase(ERK)1/2 and c AMP response element binding protein(CREB) in spinal cord of rats with chronic inflammatory visceral pain(CIVP), and to explore the central mechanism of HPM in treating CIVP.METHODS Male Sprague-Dawley rats were randomized into normal, model, HPM, sham-HPM, MEK-inhibitor and dimethyl sulfoxide(DMSO) groups. The CIVP model was established using an enema mixture of trinitrobenzene sulfonic acid and ethanol. HPM was applied at bilateral Tianshu(ST25) and Qihai(CV6) acupoints in the HPM group, while in the sham-HPM group, moxa cones and herb cakes were only placed on the same points but not ignited. The MEK-inhibitor and DMSO groups received L5-L6 intrathecal injection of U0126 and 30% DMSO, respectively. Abdominal withdrawal reflex(AWR), mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL) were applied for the assessment of pain behavior. The colonic tissue was observed under an optical microscope after hematoxylin-eosin staining. Expression of phosphor(p)MEK1, p ERK1/2 and p CREB in rat spinal cord was detected using Western blotting. The levels of MEK, ERK and CREB m RNA in rat spinal cord were detected using real-time polymerase chain reaction. RESULTS Compared with the normal group, the AWR scores were increased significantly(P < 0.01) and the MWT and TWL scores were decreased significantly(P < 0.05) in the model, sham-HPM and DMSO groups. Compared with the model group, the AWR scores were decreased significantly(P < 0.01) and the MWT and TWL scores were increased significantly in the HPM and MEK-inhibitor groups(P < 0.05). Compared with the sham-HPM and DMSO groups, the AWR scores were decreased significantly(P < 0.01) and the MWT and TWL scores were increased significantly(P < 0.05) in the HPM and MEK-inhibitor groups. Compared with the normal group, the expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were increased significantly in the model, sham-HPM and DMSO groups(P < 0.01 or < 0.05). Compared with the model group, the expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups(P < 0.01 or < 0.05). Compared with the sham-HPM and DMSO groups, expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups(P < 0.01 or < 0.05). CONCLUSION HPM down-regulates protein phosphorylation of MEK1, ERK1/2 and CREB, and m RNA expression of MEK, ERK and CREB, inhibiting activation of the MEK/ERK/CREB signaling pathway in the spinal cord of CIVP rats, which is possibly a critical central mechanism of the analgesic effect of HPM.