Surgery‐induced changes in rat IL‐1β and acetylcholine metabolism: role of physostigmine

Pharmacological enhancement of cholinergic activity following administration of physostigmine is known to induce protective effects generally. However, it is unclear whether the effect of physostigmine on inflammation and acetylcholine (ACh) metabolism is related to different types of surgical intervention or anaesthesia alone. To investigate this, rats were subjected to partial liver resection (PLR) or sham surgery, with a control group receiving anaesthesia alone. Half of each treatment group received a single intra‐operative dose of physostigmine (0.04 mg/kg); the others received placebo. Acetylcholinesterase (AChE) activity and plasma and brain concentrations of interleukin (IL)‐1β and ACh were determined. Both PLR and sham operation induced a time‐dependent increase in plasma concentrations of IL‐1β compared with rats receiving anaesthesia alone (3.9‐ and 4.8‐fold increases, respectively). In the brain, IL‐1β concentrations had increased approximately twofold after surgery compared with the control group. Blood AChE was transiently decreased after surgery. Brain AChE activity increased 1.3‐fold (P = 0.014) only after PLR; consequently, cerebral ACh concentrations were significantly reduced. Physostigmine administration significantly reduced IL‐1β and AChE levels. Cerebral ACh concentrations were markedly increased from 544 ± 122 ng/mg protein following placebo administration to 654 ± 93 ng/mg protein after physostigmine administrations (P < 0.001). We conclude that a single dose of physostigmine intra‐operatively has a sustained anti‐inflammatory effect (up to 120 min after injection) that is especially pronounced under the conditions of PLR surgery. In addition to its protective peripheral action, physostigmine exerts a neuroprotective action by increasing levels of the neurotransmitter ACh.     

Impact of non‐cardiovascular surgery on reactive hyperaemia and arterial endothelial function

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Effects of betamethasone on neuropathic pain in a rat spare nerve injury model

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Does dexmedetomidine have a cardiac protective effect during non‐cardiac surgery? A randomised controlled trial

This study was designed to determine the effects of dexmedetomidine on perioperative myocardial injury by observing peripheral circulatory changes in response to tracheal intubation and extubation, myocardial enzyme levels, myocardial ischaemia improvements, cardiovascular adverse events and cytokines in patients with coronary heart disease (CHD) undergoing non‐cardiac surgery. This study was a prospective, randomized, double‐blind trial. Eighty patients having CHD were scheduled for elective hip‐replacement surgery and randomly allocated to receive a loading dose of 1 μg/kg dexmedetomidine followed by a 0.2 μg/kg per h infusion (Dex group; n = 40) or normal saline (control group; n = 40). Systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, rate–pressure product and changes in ST‐T segment on the electrocardiogram were recorded every 5 min during surgery. Serum creatine kinase‐MB (CK‐MB), cardiac troponin I (cTnI), glycogen phosphorylase BB (GP‐BB), interleukin (IL)‐6 and tumour necrosis factor (TNF)‐α protein levels were determined preoperatively, at the end of surgery and 12 and 24 h after surgery. The improvement rate of myocardial ischaemia was higher in the Dex than control group (87.5% vs 32.5%, respectively; P < 0.05). In addition, the Dex group had lower serum CK‐MB, IL‐6, cTnI and GP‐BB concentrations than the control group (P < 0.05). There was no significance difference in TNF‐α between the two groups (P > 0.05). Dexmedetomidine can reduce myocardial injury and cytokine levels in patients with CHD undergoing non‐cardiac surgery.     

Resveratrol and vitamin E rescue valproic acid‐induced teratogenicity: The mechanism of action

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Supplementation of the maternal diet during pregnancy with chocolate and fructose interacts with the high‐fat diet of the young to facilitate the onset of metabolic disorders in rat offspring

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Tracking anti‐fibrotic pathways of nilotinib and imatinib in experimentally induced liver fibrosis: An insight

The tyrosine kinase inhibitors imatinib and nilotinib have been suggested to have promising antifibrotic activity in experimental models of liver fibrosis. The aim of the present study was to investigate new pathways underlying this beneficial effect. Hepatic injury was induced in male Wistar rats by intraperitoneal injection of CCl₄ for 12 weeks. During the last 8 weeks of treatment, rats were also injected daily intraperitoneally with 20 mg/kg imatinib or 20, 10 or 5 mg/kg nilotinib. At the end of treatment, effects on fibrosis were assessed by measuring serum fibrotic markers and profibrogenic cytokines, as well as by histopathological examination. Possible anti‐inflammatory effects were estimated by measuring levels of inflammatory cytokines in liver tissue. Liver expression of α‐smooth muscle actin, transforming growth factor (TGF)‐β1 antibodies and platelet‐derived growth factor receptor β (PDGFRβ) was evaluated by immunohistochemical staining techniques. Nilotinib (5 and 10 mg/kg) significantly (P < 0.05) decreased all serum fibrotic markers measured, but 20 mg/kg of either nilotinib or imatinib had limited effects. At all doses tested, nilotinib significantly (P < 0.05) decreased the CCl₄‐induced increases in tissue inflammatory cytokines. Furthermore, 5 and 10 mg/kg nilotinib significantly decreased TGF‐β1 levels and tissue expression of its antibody, as well expression of PDGFRβ. In conclusion, low doses (5 and 10 but not 20 mg/kg) of nilotinib, rather than imatinib, can control hepatic fibrosis by regulating levels of proinflammatory cytokines, primarily interleukin (IL)‐1 and IL‐6. Nilotinib also controls the signalling pathways of profibrogenic cytokines by lowering TGF‐β1 levels and decreasing expression of PDGFRβ.     

Expression of DCUN1D1 in laryngeal squamous cell carcinoma and its inhibiting effect on TU‐177 cells after interfered by RNA

Expression of DCUN1D1 in laryngeal squamous cell carcinoma (LSCC) and its inhibition by small interfering RNA (siRNA) target in the TU‐177 cells was investigated. Immunohistochemistry was used to detect the expression level of DCUN1D1 in LSCC tissue in 140 cases and to analyze its relationship with clinical pathological characteristics. siRNA expression plasmid targeting DCUN1D1 was constructed and transferred into TU‐177 cells. The effect of siRNA target DCUN1D1 gene silencing on proliferation, invasion and migration of TU‐177 cells were observed by MTS assay and Transwell experiment. The expression levels of focal adhesion kinase (FAK) and matrix metalloproteinase‐2(MMP‐2) were detected by western blot. Expression level of DCUN1D1 protein increased significantly in T3 + T4, N+, and III + IV stages of LSCC patients (P < .05). After DCUN1D1 was targeted by siRNA, the DCUN1D1 protein level decreased 67% in siRNA‐3 group, where average absorbance value was lower than the control and blank group with significant difference(F = 6.076, P < .05) in MTS assay, meantime migration, and invasion cells in each vision were the same (F = 19.851, F = 25.454, P < .01) in the Transwell experiment. The expression level of FAK and MMP‐2 was significantly down‐regulated in siRNA‐3 group (F = 28.896, F = 40.240, P < .01). DCUN1D1 is associated with progression and prognosis of LSCC. After siRNA based target on DCUN1D1, TU‐177 cells growth was inhibited and invasion of malignant tumour was diminished by reducing the expression of FAK and MMP‐2. DCUN1D1 is could become a potential new target for the treatment of LSCC.     

Withdrawal from long‐term use of zopiclone,zolpidem and temazepam may improve perceived sleep and quality of life in older adults with primary insomnia

Long‐term use of benzodiazepines or benzodiazepine receptor agonists is widespread, although guidelines recommend short‐term use. Only few controlled studies have characterized the effect of discontinuation of their chronic use on sleep and quality of life. We studied perceived sleep and quality of life in 92 older (age 55‐91 years) outpatients with primary insomnia before and after withdrawal from long‐term use of zopiclone, zolpidem or temazepam (BZDA). BZDA was withdrawn during 1 month, during which the participants received psychosocial support and blindly melatonin or placebo. A questionnaire was used to study perceived sleep and quality of life before withdrawal, and 1 month and 6 months later. 89 participants completed the 6‐month follow‐up. As melatonin did not improve withdrawal, all participants were pooled and then separated based solely on the withdrawal results at 6 months (34 Withdrawers. 55 Nonwithdrawers) for this secondary analysis. At 6 months, the Withdrawers had significantly (P < 0.05) shorter sleep‐onset latency and less difficulty in initiating sleep than at baseline and when compared to Nonwithdrawers. Compared to baseline, both Withdrawers and Nonwithdrawers had at 6 months significantly (P < 0.05) less fatigue during the morning and daytime. Stress was alleviated more in Withdrawers than in Nonwithdrawers (P < 0.05). Satisfaction with life and expected health 1 year later improved (P < 0.05) in Withdrawers. In conclusion, sleep disturbances, daytime fatigue and impaired quality of life may resolve within 6 months of BZDA withdrawal. These results encourage withdrawal from chronic use of benzodiazepine‐type hypnotics, particularly in older subjects.     

Risk factors for linezolid‐induced thrombocytopenia in patients without haemato‐oncologic diseases

This study aimed to describe the occurrence and to evaluate the predictive factors of thrombocytopenia caused by parenteral linezolid in hospitalised patients without haemato‐oncologic diseases. Using electronic medical records, a retrospective safety evaluation was performed among all hospitalised adult patients who received parenteral linezolid therapy between January 2005 and June 2016. Of all identified 264 patients with an average age of 63.4 (SD 15.8) years, thrombocytopenia occurred at a rate of 29.2% after an average of 11.2 (SD 7.4) days of the initiation of linezolid therapy. Significant predictive factors for thrombocytopenia included the duration of linezolid therapy longer than or equal to 7 days (adjusted odds ratios [ORs] 7.25, 19.51 and 28.80; 95% confidence intervals [CIs] 1.92‐27.38, 4.76‐79.95 and 6.48‐127.92 for 7‐13 days, 14‐20 days and ≥21 days, respectively; P < 0.01 for all values), baseline platelet count <150 × 10³/mm³ (adjusted OR, 5.08; 95% CI, 2.06‐12.55; P < 0.001), creatinine clearance <30 mL/min (adjusted OR, 4.19; 95% CI, 1.59‐11.06; P = 0.004) and concurrent low‐dose aspirin therapy (adjusted OR, 2.99; 95% CI, 1.26‐7.08; P = 0.013). Baseline platelet count less than 150 × 10³/mm³ was an independent predictor of early‐onset (≤6 days) thrombocytopenia (adjusted OR, 5.07; 95% CI, 1.46‐17.58; P = 0.011). Closer monitoring of platelet count is required in patients who receive parenteral linezolid therapy for 7 days or more, and have low baseline platelet counts or impaired renal function.     

Bone metabolism markers: Indicators of loading dose intravenous ibandronate treatment for bone metastases from breast cancer

To investigate the changes in bone metabolism markers after second‐line treatment with loading dose intravenous (i.v.) ibandronate in patients with bone metastases (BM) from breast cancer, 80 patients were enrolled in this study during January 2010 to April 2014. All the patients were treated with a second‐line loading dose ibandronate for advanced breast cancer with BM and moderate‐to‐severe bone pain. Ibandronate (6 mg) was intravenously administered on three consecutive days followed by maintenance treatment every 3‐4 weeks. Clinical data, including pain score, Karnofsky performance status (KPS) score, and changes in bone metabolism markers, were analyzed. Sixty‐two patients were included in the final analysis. Compared with their pre‐treatment scores, patients exhibited significantly increased KPS scores (P < .01) and a reduced dose of analgesic medication (oxycodone) (P < .01) after 3 and 6 weeks’ post‐treatment. The levels of serum bone alkaline phosphatase (BAP), tartrate‐resistant acid phosphatase (TRACP‐5b), and cross‐linked carboxy‐terminal telopeptide of type I collagen (ICTP) were significantly reduced after 3 and 6 weeks’ post‐treatment (P < .001). Aside from a few adverse events, no liver or renal toxicity was observed. Bone metabolism markers decreased by varying degrees after treatment with a loading dose of ibandronate in patients with BM from breast cancer. It might be convenient using bone metabolism markers to potentially evaluate the efficacy of bisphosphonates treatment for bone metastasis.     

Mycophenolate mofetil improves renal haemodynamics,microvascular oxygenation,and inflammation in a rat model of supra‐renal aortic clamping‐mediated renal ischaemia reperfusion injury

Ischaemia/reperfusion (I/R) is one of the main causes of acute kidney injury (AKI), which is characterized by sterile inflammation and oxidative stress. Immune cell activation can provoke overproduction of inflammatory mediators and reactive oxygen species (ROS), leading to perturbation of the microcirculation and tissue oxygenation associated with local and remote tissue injury. This study investigated whether the clinically employed immunosuppressant mycophenolate mofetil (MMF) was able to reduce I/R‐induced renal oxygenation defects and oxidative stress by preventing sterile inflammation. Rats were divided into three groups (n=6/group): (1) a sham‐operated control group; (2) a group subjected to renal I/R alone (I/R); and (3) a group subjected to I/R and MMF treatment (20 mg/kg prior to I/R) (I/R+MMF). Ischaemia was induced by a vascular occluder placed on the abdominal aorta for 30 minutes, followed by 120 minutes of reperfusion. Renal I/R deteriorated renal oxygenation (P<.001) and oxygen delivery (P<.01), reduced creatinine clearance (P<.01) and tubular sodium reabsorption (P<.001), and increased iNOS, renal tissue injury markers (P<.001), and IL‐6 (P<.001). Oral MMF administration prior to insult restored renal cortical oxygenation (P<.05) and iNOS, renal injury markers, and inflammation parameters (P<.001) to near‐baseline levels without affecting renal function. MMF exerted a prophylactic effect on renal microvascular oxygenation and abrogated tissue inflammation and renal injury following lower body I/R‐induced AKI. These findings may have clinical implications during major vascular or renal transplant surgery.     

Sex Difference in Formation of Propofol Metabolites: A Replication Study

Women recover faster from propofol anaesthesia and have been described to have a higher incidence of awareness during surgery, compared to men – an effect that may be inherent in sex differences in propofol metabolism. In an observational study, 98 ASA I‐II patients treated with continuous propofol infusion were recruited. The associations between sex and CYP2B6 and UGT1A9 polymorphisms with dose‐ and weight‐adjusted area under the total plasma level time curves (AUC) for propofol, and its metabolites propofol glucuronide (PG), 4‐hydroxypropofol (OHP) and hydroxyl glucuronide metabolites 4‐hydroxypropofol‐1‐O‐β‐D‐glucuronide (Q1G) and 4‐hydroxypropofol‐4‐O‐β‐D‐glucuronide (Q4G), were analysed. Significantly higher AUC of PG (1.3 times, p = 0.03), Q1G (2.9 times, p < 0.001), Q4G (2.4 times, p < 0.01) and OHP (4.6 times, p = 0.01) were found in women (n = 53) than in men (n = 45) after intravenous infusion of propofol using target‐controlled infusion system. There was, however, no significant impact of gene polymorphisms on propofol biotransformation. The results, which are supported by a previous pilot study using a propofol bolus dose, suggest that, compared to men, more rapid propofol metabolism may occur in women – a factor that may contribute to the mentioned differences in the efficacy of propofol anaesthesia between male and female patients.     

升压药物预注射对全凭静脉麻醉下腹部手术患者升压反应性和术后恢复的影响

目的 探讨全凭静脉麻醉下腹部手术中预注射不同升压药物对患者升压反应性、手术指标、不良反应指标、脑电双频指数(bispectral index,BIS)及复苏时间的影响。方法 选择中国人民解放军联勤保障部队第九八八医院择期行下腹部手术患者300例,按照不同预注射药物分为生理盐水组、麻黄碱组、去氧肾上腺素组,各100例,所有患者均行全凭静脉麻醉。记录麻醉诱导前(T0)、注射药物后1 min(T1)、注射药物后3 min(T2)、注射药物后5 min(T3)、注射药物后7 min(T4)、注射药物后9 min(T5)时患者收缩压(systolic blood pressure,SBP)、舒张压(diastolic blood pressure,DBP)、平均动脉压(mean arterial pressure,MAP)、心率(heart rate,HR)、心输出量(cardiac output,CO)、外周血管阻力(systemic vascular resistence,SVR)、每搏量变异度(stroke volume variation,SVV)等血流动力学指标;记录患者术中低血压、高...     

丁丙诺啡复合罗哌卡因对前交叉韧带重建术后镇痛的影响

目的 探讨盐酸丁丙诺啡注射液复合盐酸罗哌卡因注射液收肌管阻滞用于前交叉韧带重建术后镇痛的临床疗效。方法 选择2022年4~10月沈阳市骨科医院择期全麻下行单侧前交叉韧带重建手术治疗的40例患者,按照随机数字表法将40例患者分为对照组和治疗组,每组20例。两组均在超声引导下行收肌管阻滞,对照组注射0.5%盐酸罗哌卡因注射液20 mL+生理盐水1 mL,治疗组注射0.5%盐酸罗哌卡因注射液20 mL+盐酸丁丙诺啡注射液1 mL(0.15 mg)。分别记录两组患者术后2、6、12、24 h的VAS评分、镇痛持续时间和镇痛药物用量。结果 治疗组患者术后12、24 h静息和运动VAS评分明显低于对照组,差异有统计学意义(P<0.05)。治疗组的镇痛持续时间显著长于对照组,差异有统计学意义(P<0.05)。治疗组术后24 h地佐辛用量明显少于对照组,差异有统计学意义(P<0.05)。结论 盐酸丁丙诺啡注射液可作为盐酸罗哌卡因注射液收肌管阻滞的辅助药,为前交叉韧带重建手术提供满意的术后镇痛,且术后并发症少,有利于患者的术后康复。     

Assessment of Vascular Effects of Tamoxifen and Its Metabolites on the Rat Perfused Hindquarter Vascular Bed

Abstract: Tamoxifen has been suggested to produce beneficial cardiovascular effects, although the mechanisms for these effects are not fully known. Moreover, although tamoxifen metabolites may exhibit 30–100 times higher potency than the parent drug, no previous study has compared the effects produced by tamoxifen and its metabolites on vascular function. Here, we assessed the vascular responses to acetylcholine and sodium nitroprusside on perfused hindquarter vascular bed of rats treated with tamoxifen or its main metabolites (N‐desmethyl‐tamoxifen, 4‐hydroxy‐tamoxifen, and endoxifen) for 2 weeks. Plasma and whole‐blood thiobarbituric acid reactive substances (TBARS) concentrations were determined using a fluorometric method. Plasma nitrite and NOx (nitrite + nitrate) concentrations were determined using an ozone‐based chemiluminescence assay and Griess reaction, respectively. Treatment with tamoxifen reduced the responses to acetylcholine (pD₂ = 2.2 ± 0.06 and 1.9 ± 0.05 after vehicle and tamoxifen, respectively; P < 0.05), while its metabolites improved these responses (pD₂ = 2.5 ± 0.04 after N‐desmethyl‐tamoxifen, 2.5 ± 0.03 after 4‐hydroxy‐tamoxifen, and 2.6 ± 0.08 after endoxifen; P < 0.01). Tamoxifen and its metabolites showed no effect on endothelial‐independent responses to sodium nitroprusside (P > 0.05). While tamoxifen treatment resulted in significantly higher plasma and whole blood lipid peroxide levels (37% and 62%, respectively; both P < 0.05), its metabolites significantly decreased lipid peroxide levels (by approximately 50%; P < 0.05). While treatment with tamoxifen decreased the concentrations of markers of nitric oxide formation by approximately 50% (P < 0.05), tamoxifen metabolites had no effect on these parameters (P > 0.05). These results suggest that while tamoxifen produces detrimental effects, its metabolites produce counteracting beneficial effects on the vascular system and on nitric oxide/reactive oxygen species formation.     

Solidagenone from Solidago chilensis Meyen inhibits skin inflammation in experimental models

Solidagenone (SOL) is a labdane‐type diterpenoid found in Solidago chilensis, a plant traditionally used to treat skin diseases, kidney pain and ovarian inflammation. In this study, the topical anti‐inflammatory activity of SOL was evaluated using in vivo and in silico assays. Croton oil‐, arachidonic acid (AA)‐ and phenol‐induced ear oedema mouse models were applied in the in vivo studies. Myeloperoxidase (MPO) and N‐acetyl‐β‐D‐glucosaminidase (NAG) activities and tumour necrosis factor alpha (TNF‐α), interleukin‐6 (IL‐6) and nitric oxide (NO) levels were determined, as well as histopathological analyses were conducted. Interaction profiles between SOL and cyclooxygenase‐1 (COX‐1), cyclooxygenase‐2 (COX‐2), glucocorticoid receptor, estradiol‐17‐β‐dehydrogenase and prostaglandin‐E(2)‐9‐reductase were established using molecular docking. SOL significantly inhibited croton oil‐, AA‐ and phenol‐induced ear oedema (P < .001) at doses of 0.1, 0.5 and 1.0 mg/ear. The MPO and NAG activities and TNF‐α, IL‐6 and NO levels were decreased (P < .001). The histopathological data revealed that inflammatory parameters (oedema thickness, leucocyte infiltration and vasodilatation) were reduced by treatment with SOL at doses of 0.1, 0.5 and 1.0 mg/ear. The docking study showed that SOL interacts with COX‐1 and prostaglandin‐E(2)‐9‐reductase through hydrogen bonding, inhibiting these enzymes. These results indicate that SOL may be a promising compound for the treatment of cutaneous inflammatory disorders and has potential as a topical anti‐inflammatory agent.     

丁丙诺啡复合罗哌卡因对髋部骨折手术患者镇痛和髋关节活动度的影响

目的 考察盐酸丁丙诺啡注射液复合盐酸罗哌卡因注射液用于髂筋膜间隙阻滞对老年患者髋部骨折手术术后镇痛效果。方法 选取2020年3月—2022年3月在中化二建集团医院行髋部骨折手术62例患者,将所有患者随机分为对照组和治疗组,每组各31例。超声引导下行髂筋膜间隙阻滞。对照组注入0.25%盐酸罗哌卡因注射液40 mL。治疗组注入0.15mg盐酸丁丙诺啡注射液+0.25%盐酸罗哌卡因注射液40 mL。记录两组术后12、24、36、48、60、72 h各时间点静息和活动状态下的VAS评分和术后7 d髋关节活动度（ROM）。结果 与同组24 h静息状态和活动状态比较,36、48、60、72 h时对照组和治疗组VAS评分均显著降低,差异有统计学意义（P<0.05）。治疗组术后静息状态VAS评分在12、24、36、48 h低于对照组,差异有统计学意义（P<0.05）。治疗组在12、24、36、48、60、72 h术后活动状态VAS评分低于对照组,差异有统计学意义（P<0.05）。与同组1 d比较,术后7 d每日髋关节ROM均显著升高,差异有统计学意义（P<0.05）;与对照组同...     

Effects of JTV‐519 on stretch‐induced manifestations of mechanoelectric feedback

JTV‐519 is a 1,4‐benzothiazepine derivative with multichannel effects that inhibits Ca²⁺ release from the sarcoplasmic reticulum and stabilizes the closed state of the ryanodine receptor, preventing myocardial damage and the induction of arrhythmias during Ca²⁺ overload. Mechanical stretch increases cellular Na⁺ inflow, activates the reverse mode of the Na⁺/Ca²⁺ exchanger, and modifies Ca²⁺ handling and myocardial electrophysiology, favoring arrhythmogenesis. This study aims to determine whether JTV‐519 modifies the stretch‐induced manifestations of mechanoelectric feedback. The ventricular fibrillation (VF) modifications induced by acute stretch were studied in Langendorff‐perfused rabbit hearts using epicardial multiple electrodes under control conditions (n=9) or during JTV‐519 perfusion: 0.1 μmol/L (n=9) and 1 μmol/L (n=9). Spectral and mapping techniques were used to establish the baseline, stretch and post‐stretch VF characteristics. JTV‐519 slowed baseline VF and decreased activation complexity. These effects were dose‐dependent (baseline VF dominant frequency: control=13.9±2.2 Hz; JTV 0.1 μmol/L=11.1±1.1 Hz, P<.01; JTV 1 μmol/L=6.6±1.1 Hz, P<.0001). The stretch‐induced acceleration of VF (control=38.8%) was significantly reduced by JTV‐519 0.1 μmol/L (19.8%) and abolished by JTV 1 μmol/L (−1.5%). During stretch, the VF activation complexity index was reduced in both JTV‐519 series (control=1.60±0.15; JTV 0.1 μmol/L=1.13±0.3, P<.0001; JTV 1 μmol/L=0.57±0.21, P<.0001), and was independently related to VF dominant frequency (R=.82; P<.0001). The fifth percentile of the VF activation intervals, conduction velocity and wavelength entered the multiple linear regression model using dominant frequency as the dependent variable (R=−.84; P<.0001). In conclusion, JTV‐519 slowed and simplified the baseline VF activation patterns and abolished the stretch‐induced manifestations of mechanoelectric feedback.     

Intradermal glutamate and capsaicin injections: Intra‐ and interindividual variability of provoked hyperalgesia and allodynia

Intradermal injections of glutamate and capsaicin are attractive to use in human experimental pain models because hyperalgesia and allodynia mimic isolated aspects of clinical pain disorders. The aim of the present study was to investigate the reproducibility of these models. Twenty healthy male volunteers (mean age 24 years; range 18–38 years) received intradermal injections of glutamate and capsaicin in the volar forearm. Magnitudes of secondary pinprick hyperalgesia and brush‐evoked allodynia were investigated using von Frey filaments (gauges 10, 15, 60 and 100 g) and brush strokes. Areas of secondary hyperalgesia and allodynia were quantified immediately after injection and after 15, 30 and 60 min. Two identical experiments separated by at least 7 days were performed. Reproducibility across and within volunteers (inter‐ and intra‐individual variation, respectively) was assessed using intraclass correlation coefficient (ICC) and coefficient of variation (CV). Secondary pinprick hyperalgesia was observed as a marked increase in the visual analogue scale (VAS) response to von Frey gauges 60 and 100 g (P < 0.001) after glutamate injection. For capsaicin, secondary pinprick hyperalgesia was detected with all von Frey gauges (P < 0.001). Glutamate evoked reproducible VAS response to all von Frey gauges (ICC > 0.60) and brush strokes (ICC > 0.83). Capsaicin injection was reproducible for secondary hyperalgesia (ICC > 0.70) and allodynia (ICC > 0.71). Intra‐individual variability was generally lower for the VAS response to von Frey and brush compared with areas of secondary hyperalgesia and allodynia. In conclusion, glutamate and capsaicin yield reproducible hyperalgesic and allodynic responses, and the present model is well suited for basic research, as well as for assessing the modulation of central phenomena.