Investigating epithelial-neuronal signaling contribution in visceral pain through colon organoid-dorsal root ganglion neuron co-cultures

Abdominal pain is a common symptom associated with irritable bowel syndrome and inflammatory bowel diseases(IBDs),affecting about 20%of the global population(Grundy et al.,2019).Current pain therapies are poorly effective on visceral pain of intestinal origin and present several side effects,hence the need to identify novel molecular and cellular targets for drug development.

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.

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.

Drugs used for pain management in gastrointestinal surgery and their implications

Pain is the predominant symptom troubling patients.Pain management is one of the most important aspects in the management of surgical patients leading to early recovery from surgical procedures or in patients with chronic diseases or malignancy.Various groups of drugs are used for dealing with this;however,they have their own implications in the form of adverse effects and dependence.In this article,we review the concerns of different pain-relieving medicines used postoperatively in gastrointestinal surgery and for malignant and chronic diseases.

Acupuncture and moxibustion for visceral pain

Totally three articles focusing on"analgesic action of suspended moxibustion effect in visceral hypersensitivity rats with irritable bowel syndrome,and changes in prokineticin 1 and prokineticin receptor 1 expression in the spinal cord,enkephalins in the spinal cord and prokineticin-1 and prokineticin receptor-1 in the colon tissue during the analgesic progress"were

Electroacupuncture Attenuates Visceral Pain and Reverses Upregulation of TRPV1 Expression in Adult Rats with Neonatal Maternal Deprivation

Irritable bowel syndrome (IBS) is characterized by chronic visceral hypersensitivity that companied by altered bowel movement. However, the treatment options are very limited. The aim of this study was to investigate effects of electroacupuncture (EA) on visceral hypersensitivity in a rat model of IBS and to explore the underlying mechanisms of EA effects. Visceral hypersensitivity was established by neonatal maternal deprivation (NMD) in male rats on postnatal days 2 - 15. Behavioral experiments were conducted at the age of 7 weeks. Treatment with EA at Zusanli (stomach-36, ST-36) significantly reduced abdominal withdrawal reflex (AWR) scores in NMD rats but not in age-matched healthy control rats. In addition, EA treatment hyperpolarized resting membrane potentials, increased the rheobase and reduced the numbers of action potentials evoked by 2 and 3 times rheobase current stimulation of dorsal root ganglion (DRG) neurons innervating the colon. NMD markedly enhanced expression of TRPV1 in colon related DRGs while EA treatment drastically suppressed the expression of TRPV1 in DRGs of NMD rats. These data suggest that EA treatment produced an analgesic effect, which might be mediated at least in a part by suppression of TRPV1 expression and by inhibition of neuronal excitability of primary sensory neurons in rats with chronic visceral pain.

Serotonin transporter and cholecystokinin in diarrhea-predominant irritable bowel syndrome: Associations with abdominal pain, visceral hypersensitivity and psychological performance

BACKGROUND Visceral hypersensitivity and psychological performance are the main pathophysiological mechanisms of irritable bowel syndrome(IBS).Previous studies have found that cholecystokinin(CCK)can enhance colon movement and that serotonin transporter(SERT)is a transmembrane transport protein with high affinity for 5-hydroxytryptamine,which can rapidly reuptake 5-hydroxytryptamine and then regulate its action time and intensity.We speculate that SERT and CCK might play a role in the pathogenesis of diarrheapredominant IBS(IBS-D)by affecting visceral sensitivity and the brain-gut axis.AIM To determine SERT and CCK levels in IBS-D patients diagnosed using Rome IV criteria and to analyze their associations with abdominal pain,visceral hypersensitivity and psychological performance.METHODS This study collected data from 40 patients with IBS-D at the China-Japan Friendship Hospital from September 2017 to April 2018 and 18 healthy controls.The severity of abdominal pain,visceral sensitivity and psychological performance were evaluated in IBS-D patients and healthy controls,the levels of SERT and CCK in plasma and colonic mucosa were evaluated,and the correlations between them were analyzed.RESULTS There were significant differences in the initial sensation threshold(31.00±8.41 mL vs 52.22±8.09 mL,P<0.001),defecating sensation threshold(51.75±13.57 mL vs 89.44±8.73 mL,P<0.001)and maximum tolerable threshold(97.25±23.64 mL vs 171.11±20.83 mL,P<0.001)between the two groups.IBS-D patients had more severe anxiety(7.78±2.62 vs 2.89±1.02,P<0.001)and depressive(6.38±2.43 vs 2.06±0.73,P<0.001)symptoms than healthy controls.Significant differences were also found in mucosal CCK(2.29±0.30 vs 1.66±0.17,P<0.001)and SERT(1.90±0.51 vs 3.03±0.23,P<0.001)between the two groups.There was a significant positive correlation between pain scores and mucosal CCK(r=0.96,0.93,0.94,P<0.001).Significant negative correlations between anxiety(r=-0.98;P<0.001),depression(r=-0.99;P<0.001),pain evaluation(r=-0.96,-0.93,-0.95,P<0.001)and mucosal SERT were observed.CONCLUSION IBS-D patients had psychosomatic disorders and visceral hypersensitivity.SERT and CCK might be involved in the pathogenesis of IBS-D by regulating the braingut axis and affecting visceral sensitivity.This provides a new potential method for identifying a more specific and effective therapeutic target.

Effect of Preemptive Ketamine Administration on Postoperative Visceral Pain after Gynecological Laparoscopic Surgery

The pain following gynecological laparoscopic surgery is less intense than that following open surgery; however, patients often experience visceral pain after the former surgery. The aim of this study was to determine the effects of preemptive ketamine on visceral pain in patients undergoing gynecological laparoscopic surgery. Ninety patients undergoing gynecological laparoscopic surgery were randomly assigned to one of three groups. Group 1 received placebo. Group 2 was intravenously injected with preincisional saline and local infiltration with 20 m L ropivacaine（4 mg/m L） at the end of surgery. Group 3 was intravenously injected with preincisional ketamine（0.3 mg/kg） and local infiltration with 20 m L ropivacaine（4 mg/m L） at the end of surgery. A standard anesthetic was used for all patients, and meperidine was used for postoperative analgesia. The visual analogue scale（VAS） scores for incisional and visceral pain at 2, 6, 12, and 24 h, cumulative analgesic consumption and time until first analgesic medication request, and adverse effects were recorded postoperatively. The VAS scores of visceral pain in group 3 were significantly lower than those in group 2 and group 1 at 2 h and 6 h postoperatively（P〈0.05 and P〈0.01, respectively）. At 2 h and 6 h, the VAS scores of incisional pain did not differ significantly between groups 2 and 3, but they were significantly lower than those in group 1（P〈0.01）. Groups 1 and 2 did not show any differences in visceral pain scores at 2 h and 6 h postoperatively. Moreover, the three groups showed no statistically significant differences in visceral and incisional pain scores at 12 h and 24 h postoperatively. The consumption of analgesics was significantly greater in group 1 than in groups 2 and 3, and the time to first request for analgesics was significantly longer in groups 2 and 3 than in group 1, with no statistically significant difference between groups 2 and 3. However, the three groups showed no significant difference in the incidence of shoulder pain or adverse effects. Preemptive ketamine may reduce visceral pain in patients undergoing gynecological laparoscopic surgery.

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.

Translational pain research: Evaluating analgesic effect in experimental visceral pain models

Deep visceral pain is frequent and presents major challenges in pain management, since its pathophysiology is still poorly understood. One way to optimize treatment of visceral pain is to improve knowledge of the mechanisms behind the pain and the mode of action of analgesic substances. This can be achieved through stand-ardized experimental human pain models. Experimental pain models in healthy volunteers are advantageous for evaluation of analgesic action, as this is often diff icult to assess in the clinic because of confounding factors such as sedation, nausea and general malaise. These pain models facilitate minimizing the gap between knowledge gained in animal and human clinical studies. Combining experimental pain studies and pharmacokinetic stud- ies can improve understanding of the pharmacokinetic-pharmacodynamic relationship of analgesics and, thus, provide valuable insight into optimal clinical treatment of visceral pain. To improve treatment of visceral pain, it is important to study the underlying mechanisms of pain and the action of analgesics used for its treatment. An experimental pain model activates different modalities and can be used to investigate the mechanism of action of different analgesics in detail. In combination with pharmacokinetic studies and objective assessment such as electroencephalography, new information re-garding a given drug substance and its effects can be obtained. Results from experimental human visceral pain research can bridge the gap in knowledge between animal studies and clinical condition in patients suffering from visceral pain, and thus constitute the missing link in translational pain research.

Pretreatment of emulational manual acupuncture versus electroacupuncture against visceral traction pain in rats

BACKGROUND： Acupuncture and moxibustion against visceral noxious stimulation present different mechanisms in the peripheral and central nervous systems, involving release of neurotransmitter substance P, acetylcholine esterase, leucine-enkephalin, and c-Fos protein expression. However, there are few reports addressing changes in neurotransmitter expression following manual acupuncture and electroacupuncture against visceral traction pain.OBJECTIVE： To explore changes in neurotransmitter expression in the ileum and protein expression in the medullary visceral zone of visceral traction pain rats undergoing pretreatment of emulational manual acupuncture, and to investigate the differences between emulational manual acupuncture and electroacupuncture.DESIGN, TIME AND SETTING： The randomized, controlled study was performed at the Biomedical Engineering Laboratory, Shanghai University of Traditional Chinese Medicine, Shanghai, China from August 2008 to July 2009.MATERIALS： G6805 electroacupuncture apparatus （Shanghai Medical Electronic Machine Factory, China） and ZSF-I acupuncture manipulation simulation therapeutic system （Chinese Medical Engineering Room, Shanghai University of Traditional Chinese Medicine, Shanghai China） were used in the present study.METHODS： A total of 40 male Sprague Dawley rats were equally and randomly assigned to sham surgery, model, emulational manual acupuncture and electroacupuncture groups. In the emulational manual acupuncture and electroacupuncture groups, emulational manual acupuncture and electroacupuncture were applied at bilateral Zusanli （ST 36） acupoints for 30 minutes, and models of visceral traction pain were established immediately.MAIN OUTCOME MEASURES： Substance P expression, c-Fos and glial fibrillary acidic protein expression were measured using immunohistochemistry. Acetylcholine esterase activity was examined utilizing a colorimetric method. Leucine-enkephalin content was detected using a radioimmune assay. Degree of pain in rats was assessed by pain score.RESULTS： Pain score, substance P expression in the ileum, acetylcholine esterase activity, expression of c-Fos protein and glial fibrillary acidic protein in the medullary visceral zone were significantly decreased following pretreatment of emulational manual acupuncture and electroacupuncture in rats with visceral traction pain （P〈0.05）. Compared with the electroacupuncture group, the leucine-enkephalin content was significantly increased, and pain score was significantly diminished in the emulational manual acupuncture group （P〈0.05）.CONCLUSION： Emulational manual acupuncture pretreatment decreases acetylcholine esterase activity, increases leucine-enkephalin release, downregulates expression of c-Fos protein and glial fibrillary acidic protein and ultimately inhibits visceral traction pain by reducing substance P release. The effectiveness in inhibiting visceral traction pain is greater when using emulational manual acupuncture compared with electroacupuncture. This is because emulational manual acupuncture effectively increases leucine-enkephalin release.

Estrogen augmented visceral pain and colonic neuron modulation in a double-hit model of prenatal and adult stress

BACKGROUND Chronic stress during pregnancy may increase visceral hyperalgesia of offspring in a sex-dependent way.Combining adult stress in offspring will increase this sensitivity.Based on the evidence implicating estrogen in exacerbating visceral hypersensitivity in female rodents in preclinical models,we predicted that chronic prenatal stress(CPS)+chronic adult stress(CAS)will maximize visceral hyperalgesia;and that estrogen plays an important role in colonic hyperalgesia.AIM The aim was to illuminate the role of estrogen in colonic hyperalgesia and its underlying mechanisms.METHODS We established a CPS plus CAS rodent model in which the balloon was used to distend the colorectum.The single-fiber recording in vivo and patch clamp experiments in vitro were used to monitor the colonic neuron’s activity.The reverse transcription-polymerase chain reaction,western blot,and immunofluorescence were used to study the effects of CPS and CAS on colon primary afferent sensitivity.We used ovariectomy and letrozole to reduce estrogen levels of female rats respectively in order to assess the role of estrogen in female-specific enhanced primary afferent sensitization.RESULTS Spontaneous activity and single fiber activity were significantly greater in females than in males.The enhanced sensitization in female rats mainly came from lowthreshold neurons.CPS significantly increased single-unit afferent fiber activity in L6-S2 dorsal roots in response.Activity was further enhanced by CAS.In addition,the excitability of colon-projecting dorsal root ganglion(DRG)neurons increased in CPS+CAS rats and was associated with a decrease in transient Atype K+currents.Compared with ovariectomy,treatment with the aromatase inhibitor letrozole significantly reduced estrogen levels in female rats,confirming the gender difference.Moreover,mice treated with letrozole had decreased colonic DRG neuron excitability.The intrathecal infusion of estrogen increased brain-derived neurotrophic factor(BDNF)protein levels and contributed to the response to visceral pain.Western blotting showed that nerve growth factor protein was upregulated in CPS+CAS mice.CONCLUSION This study adds to the evidence that estrogen-dependent sensitization of primary afferent colon neurons is involved in the development of chronic stress-induced visceral hypersensitivity in female rats.

Targeting voltage-gated sodium channels for treatment for chronic visceral pain

Voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability,and their abnormal activity is related to several pathological processes,including cardiac arrhythmias,epilepsy,neurodegenerative diseases,spasticity and chronic pain.In particular,chronic visceral pain,the central symptom of functional gastrointestinal disorders such as irritable bowel syndrome,is a serious clinical problem that affects a high percentage of the world population.In spite of intense research efforts and after the dedicated decade of pain control and research,there are not many options to treat chronic pain conditions.However,there is a wealth of evidence emerging to give hope that a more refined approach may be achievable.By using electronic databases,available data on structural and functional properties of VGSCs in chronic pain,particularly functional gastrointestinal hypersensitivity,were reviewed.We summarize the involvement and molecular bases of action of VGSCs in the pathophysiology of several organic and functionalgastrointestinal disorders.We also describe the efficacy of VGSC blockers in the treatment of these neurological diseases,and outline future developments that may extend the therapeutic use of compounds that target VGSCs.Overall,clinical and experimental data indicate that isoform-specific blockers of these channels or targeting of their modulators may provide effective and novel approaches for visceral pain therapy.

Possible implications of animal models for the assessment of visceral pain

Acute pain,provoked generally after the activation of peripheral nociceptors,is an adaptive sensory function that alerts the individual to avoid noxious stimuli.However,uncontrolled acute pain has a maladaptive role in sensory activity leading to development of a chronic pain state which persists even after the damage is resolved,or in some cases,in the absence of an initial local acute injury.Huge numbers of people suffer from visceral pain at least once during their life span,leading to substantial health care costs.Although studies reporting on the mechanism of visceral pain are accumulating,it is still not precisely understood.Therefore,this review aims to elucidate the mechanism of visceral pain through an evaluation of different animal models and their application to develop novel therapeutic approaches for treating visceral pain.To assess the nociceptive responses in viscera,several visceral pain models such as inflammatory,traction,stress and genetic models utilizing different methods of measurement have been devised.Among them,the inflammatory and traction models are widely used for studying the visceral pain mechanism of different disease conditions and post-operative surgery in humans and animals.A hapten,2,4,6-trinitrobenzene sulfonic acid(TNBS),has been extensively used as an inflammatory agent to induce visceral pain.The traction model seems to cause a strong pain stimulation and autonomic reaction and could thus be the most appropriate model for studying the underlying visceral pain mechanism and for probing the therapeutic efficacies of various anesthetic and analgesics for the treatment of visceral pain and hyperalgesia.

Treatment of Operative Pain in Visceral Cancer Surgery at CHU Gabriel Toure

The objectives were to determine the frequency of pain in cancer patients and its intensity in cancer pathologies and to evaluate the evolution of pain intensity after analgesic treatment;the effectiveness of its management study involved 121 cases of operated gastrointestinal cancers, which accounted for 85.82% (141) of operated cancers and 16.78% (721) of all operated patients;the average age of our patients was 49.93 years with extremes 17 and 78 years. Standard deviation: 15.75;with a sex ratio of 1.46. The majority of our patients had WHO III (54/121) or 44.6%;46.3% (56/121) of patients were in stage IV of the TNM classification. The main digestive cancers were cancer of the esophagus 4 cases (3.3%);of the stomach 61 cases (50.4%);of the pancreas 7 cases (5.8%);of the liver 4 cases (3.3%);gall bladder 2 cases (1.6%);colon 33 cases (27.3%);rectum 6 cases (4.9%) and hail 4 cases (3.3%). The average pain intensities were 3 to 6 hour;2 to 24 hour;1.6 to 48 hour;and 1.2 to 72 hour. The majority of our patients had a treatment protocol involving nefopam, and paracetamol was 58%. The pain was exacerbated especially during exercise. Vomiting and vein burning were the main side effects encountered.

Effect of laparoscopic radical resection of rectal cancer on gastrointestinal hormones, visceral protein and pain stress in patients

Objective: To investigate the effects of laparoscopic radical resection of rectal cancer on gastrointestinal hormones, visceral protein and pain stress. Methods: A total of 96 patients with rectal cancer radical resection from January 2017 to December 2017 in our hospital, were selected as the research objects, the patients were randomly divided into the observation group (48 cases) and the control group (48 cases). The observation group received laparoscopic radical resection of rectal cancer, while the control group underwent open radical resection of rectal cancer. The levels of gastrin (GAS), motilin (MTL), vasoactive intestinal peptide (VIP), transferrin (TRF), retinol binding protein (RbP), albumin (ALB), prealbumin (PRE), P substance (SP), bradykinin (BK), and prostaglandin-E2 (PGE2) were measured and compared in the two groups. Results: Before operation, there was no significant difference in GAS, MTL and VIP between the two groups. 1, 3, and 5 d after operation, the GAS, MTL and VIP of the two groups were significantly lower than those before operation, and the differences were statistically significant. 1, 3, and 5 d after operation, GAS of the observation group were (66.60±5.79) μmol/L, (71.95±6.16) μmol/L and (77.68±6.38) μmol/L respectively, MTL were (225.68±19.83) pg/mL, (253.76±21.42) pg/mL and (289.98±24.74) pg/mL, VIP were (1.99±0.42) μmol/L, (2.43±0.46) μmol/L, (2.80±0.51) μmol/L, respectively, which were higher than that of the control group at the same time, and the difference was statistically significant. Before operation, there was no significant difference in TRF, RbP, ALB and PRE levels in the two groups. 1, 3 and 5 d after operation, the TRF, RbP, ALB and PRE levels in the two groups were significantly lower than those before operation, and the differences were statistically significant. 1, 3 and 5 d after operation, TRF of the observation group were (1.64±0.33) ng/L, (1.44±0.30) ng/L, (1.46 ±0.32) ng/L, RbP were (19.05±3.85) mg/L, (21.83±4.26) mg/L and (24.54±4.45) mg/L respectively, and ALB were (31.49±2.54) ng/L, (28.21±2.05) ng/L and (28.43±1.99) ng/L, PRE were (0.20±0.06) ng/L, (0.16±0.05) ng/L, (0.15±0.05) ng/L, which were all higher than those in the control group at the same time, and the differences were statistically significant. Before operation, there was no significant difference in SP, BK and PGE2 between the two groups. 1, 3 and 5 d after operation, the SP, BK and PGE2 of the two groups were significantly higher than those before operation and the differences were statistically significant. 1, 3 and 5 d after operation, SP of the observation group was (7.31±0.87) μg/mL, (5.43±0.51) μg/mL and (3.10±0.24) μg/mL, BK was (9.53±0.80) μg/L, (7.81±0.79) μg/L and 6.30±0.53) pg/mL, and PGE2 were (152.42±14.80) pg/mL, (131.22±13.35) pg/mL, (117.86±11.95) pg/mL, which were all lower than those in the control group at the same time, and the differences were statistically significant. Conclusion: Laparoscopic radical resection of rectal cancer can help patients recover gastrointestinal function faster and cause less pain stress.

Research progress of pain catastrophizing in patients with lumbar disc herniation

Pain catastrophization is one of the negative emotional factors and an important psychological factor associated with patients with lumbar disc herniation(LDH).Currently,the concept of pain catastrophization of LDH is relatively mature abroad;however,there are only few research studies on this in China.To understand the status quo of pain catastrophization(PC)in patients with LDH and its influencing factors,the intervention measures of PC and their efficacy were further analyzed.In the present paper,the research status of PC at home and abroad is briefly expounded,and the influencing factors and clinical intervention measures for PC are analyzed.This paper reviews the concept of PC,the assessment tools,influencing factors,and the relevant intervention measures.In order to evaluate the pain degree of patients,understand the incidence of pain in patients,and improve the cure rate and quality of life of patients,the basic situation of patients with pain disaster is summarized to provide reference for medical personnel.

重型创伤性脑损伤去骨瓣减压应用改良Paine点穿刺监测脑室内颅内压的优势

目的探讨重型创伤性脑损伤(TBI)开颅去骨瓣减压术(DC)中应用改良Paine点穿刺行脑室内颅内压(ICP)监测探头置入的优势。方法回顾性分析2020年4月-2022年4月嘉兴市第二医院收治的48例重型TBI患者的临床资料。所有患者均行DC联合脑室内ICP监护术,按照ICP监测术式的不同,分为观察组(23例)与对照组(25例),其中观察组行DC切口内改良Paine点穿刺脑室内ICP监测探头置入术,对照组行传统DC对侧切口颅骨钻孔经Kocher点脑室内ICP监测探头置入术。比较两组术前一般资料、手术用时、术后甘露醇使用剂量及持续时间、ICP监测持续时间、术后再出血率、颅内感染率、术后3个月时格拉斯哥预后评分(GOS)。结果两组一般资料、甘露醇使用剂量、甘露醇持续时间和ICP监测持续时间比较差异均无统计学意义(P>0.05);观察组手术用时、术后再出血率、颅内感染率明显少于或低于对照组(P<0.05);两组术后3个月GOS评分比较差异无统计学意义(P>0.05)。结论相较传统的DC对侧切口颅骨钻孔经Kocher点行脑室内ICP监测探头置入术,重型脑外伤DC术中通过切口内改良Paine点穿刺行脑室内ICP监测探头置入术可缩短手术用时,降低术后再出血率、颅内感染率。

Effect of ankle versus thigh tourniquets on post-operative pain in foot and ankle surgery

BACKGROUND Tourniquets are commonly used in elective extremity orthopaedic surgery to reduce blood loss,improve visualization in the surgical field,and to potentially reduce surgical time.There is a lack of consensus in existing guidelines regarding the optimal tourniquet pressure,placement site,and duration of use.There is a paucity of data on the relationship between the site of a tourniquet and postoperative pain in foot and ankle surgery.AIM To explore the relationship between tourniquet site and intensity of post-operative pain scores in patients undergoing elective foot and ankle surgery.METHODS Retrospective analysis of prospectively collected data on 201 patients who underwent foot and ankle surgery in a single institution was undertaken.Intraoperative tourniquet duration,tourniquet pressure and site,and postoperative pain scores using Visual Analogue Score were collected in immediate recovery,at six hours and at 24 h post-op.Scatter plots were used to analyse the data and to assess for the statistical correlation between tourniquet pressure,duration,site,and pain scores using Pearson correlation coefficient.RESULTS All patients who underwent foot and ankle surgery had tourniquet pressure of 250 mmHg for ankle tourniquet and 300 mmHg for thigh.There was no correlation between the site of the tourniquet and pain scores in recovery,at six hours and after 24 h.There was a weak correlation between tourniquet time and Visual Analogue Score immediately post-op(r=0.14,P=0.04)but not at six or 24 h post-operatively.CONCLUSION This study shows that there was no statistically significant correlation between tourniquet pressure,site and postop pain in patients undergoing foot and ankle surgery.The choice of using a tourniquet is based on the surgeon's preference,with the goal of minimizing the duration of its application at the operative site.

Analgesic effects of JCM-16021 on neonatal maternal separation-induced visceral pain in rats

AIM:To investigate the pharmacological effect of JCM-16021,a Chinese herbal formula,and its underlying mechanisms.METHODS:JCM-16021 is composed of seven herbal plant materials.All raw materials of the formula were examined according to the quality control criteria listed in the Chinese Pharmacopeia(2005).In a neonatal maternal separation(NMS)model,male SpragueDawley rats were submitted to daily maternal separation from postnatal day 2 to day 14,or no specific handling(NH).Starting from postnatal day 60,rats were administered JCM-16021(2,4,8 g/kg per day)orally twice a day for 28 d.Pain threshold pressure and electromyographic activities of external oblique muscles in response to colorectal distention recorded with a Power Lab System(AD Instruments International),were tested as pain indices.Changes in serotonin(5-HT)and 5-hydroxyindoleacetic acid(5-HIAA)concentrations in the colon of rats were analyzed;the enterochromaffin cell numbers and serotonin transporter in the colon of rats were also evaluated with an immunohistochemistry method.RESULTS:NMS treatment significantly reduced pain threshold pressure(37.4±1.4 mmHg),as compared to that of NH rats(57.7±1.9 mmHg,P<0.05).After JCM-16021 treatment,the pain threshold pressure significantly increased when compared to that before treatment(34.2±0.9 mmHg vs 52.8±2.3 mmHg in the high dose group,40.2±1.6 mmHg vs 46.5±1.3 mmHg in the middle dose group,and 39.3±0.7 mmHg vs 46.5±1.6 mmHg in the low dose group,P<0.05).Also JCM-16021 significantly and dose-dependently decreased electromyographic activity to the graded colorectal distension(CRD),(the meanΔAUC values were:0.17±0.03,0.53±0.15,1.06±0.18,1.22±0.24 in the high dose group;0.23±0.04,0.68±0.17,1.27 ±0.26,1.8±0.3 in the middle dose group;and 0.29 ±0.06,0.8±0.16,1.53±0.24,2.1±0.21 in the low dose group for the pressures 20,40,60,80 mmHg),as compared to the NMS vehicle group.The meanΔAUC values were:0.57±0.12,1.33±0.18,2.57±0.37,3.08±0.37 for the pressures 20,40,60,80 mmHg(P <0.05).JCM-16021 treatment significantly reduced the 5-HT concentrations(from high,middle and low dosage groups:60.25±5.98 ng/100 mg,60.32±4.22 ng/100 mg,73.31±7.65 ng/100 mg),as compared to the NMS vehicle groups(93.11±9.85 ng/100 mg,P<0.05);and increased the 5-HIAA concentrations(after treatment,from high,middle and low dosage groups:54.24±3.27 ng/100 mg,50.34±1.26 ng/100 mg,51.37±2.13 ng/100 mg)when compared to that in the NMS vehicle group(51.75±1.98 ng/100 mg,P <0.05);but did not change the enterochromaffin cell numbers in the colon of rats.In addition,NMS rats had higher SERT expression(n=10)than NH rats(n=8,P<0.05).JCM-16021 treatment significantly decreased SERT expression when compared to the NMS group(P <0.01-0.001).CONCLUSION:JCM-16021 can attenuate visceral hypersensitivity,and this analgesic effect may be mediated through the serotonin signaling pathway in the colon of rats.