Long-latency responses of brain noradrenergic neurons to noxious stimuli are preferentially attenuated by intravenous morphine

The nucleus locus coeruleus (LC) has been strongly implicated in the processing of noxious stimuli. Consistent with this, previous studies have shown that spontaneous LC discharge is depressed by morphine. However, effects of morphine on evoked responses of LC neurons to noxious stimuli have not been systematically examined. We reported recently that responses to footshock stimuli in rat locus coeruleus neurons consist of an early (A-fiber mediated) component and a previously undescribed late (C-fiber mediated) component. In the present study, we administered analgesic doses of morphine (0.1, 0.5, or 1.0 mg/kg, i.v.) to determine the effect on A- and C-fiber components of footshock responses in LC neurons. Doses of 0.5 and 1.0 mg/kg significantly attenuated the C-fiber mediated response of LC neurons without affecting the A-fiber response component. Spontaneous LC discharge was reduced by administration of all doses of morphine. Both depressive effects of morphine were abolished by intravenous administration of naloxone. In contrast, local microinfusion of naloxone into the LC abolished the morphine-induced decrease of spontaneous discharge but did not prevent the depression of the C-fiber mediated footshock response by morphine. This indicates that the site of action for morphine's attenuation of the late LC response to footshock stimulation is outside of the LC. The results are consistent with the hypothesis that the late (C-fiber-mediated) footshock responses in locus coeruleus are involved in the processing of noxious stimuli and may contribute to anti-nociceptive mechanisms.     

Isoflurane anesthesia blunts cerebral responses to noxious and innocuous stimuli: a fMRI study

We used functional magnetic resonance imaging to determine how isoflurane affected cerebral neuronal activation resulting from noxious and innocuous stimuli. Five male volunteers were subjected to mild electrical shock and tactile stimuli applied to the hand. During low (0.7%) and moderate (1.3%) isoflurane anesthesia the stimuli were repeated and a supramaximal electrical shock was also applied. Tactile stimulation activated bilateral SI and SII, but resulted in no significant activation at low or moderate anesthesia. Electrical shock activated contralateral SI and bilateral SII; low anesthesia completely abolished this response. The supramaximal stimulus activated the caudate nucleus and bilateral thalamus at low anesthesia; these responses were diminished at moderate anesthesia. Isoflurane anesthesia blunts cerebral responses to somatosensory stimuli, and the absence of cortical activation during supramaximal stimulation suggests that noxious-induced movement is generated in lower CNS structures.     

Reduction of pain on injection of propofol: a comparison of fentanyl with lidocaine

BACKGROUND: Keloids are the result of a dysregulated wound healing process. They are characterized by the formation of excess scar tissue that proliferates beyond the boundaries of the original wound. Somatic mutations of p53 have been implicated as causal events in up to 50% of all human malignancies. In addition, p53 has been shown to play an important role in controlling cell proliferation and apoptosis. We hypothesize that mutations in p53 can lead to a hyperproliferative state that can result in keloid formation. OBJECTIVE: To detect p53 DNA mutations in tissues and cultured fibroblasts from skin lesions of 7 patients with keloids. DESIGN: The polymerase chain reaction followed by single-strand conformational polymorphism analysis and direct DNA sequencing were used to detect p53 gene mutations. SETTING: The Department of Dermatology, Henry Ford Hospital, Detroit, Mich. PATIENTS: Seven patients with keloids seen for routine surgical excision of their lesions. Normal DNA specimens were obtained from buccal smears and healthy skin samples from these patients. RESULTS: Mutations in the p53 were identified in all patients by polymerase chain reaction followed by single-strand conformational polymorphism analysis and subsequently confirmed by DNA sequencing. A mutation in exon 5 resulting in amino acid substitution was found in 1 of the patients in keloid tissue and cultured keloid fibroblasts (codon 156, CGC-->CCC, arginine-->proline). Frameshift mutations in exons 5 and 6 caused by the insertion or deletion of a nucleotide at different positions were found in 6 patients with keloids in both keloid tissues and cultured fibroblasts. Mutations in exon 4 resulting in amino acid substitution were found in all patients in both keloid tissues and cultured fibroblasts (all in codon 72, CGC-->CCC, arginine-->proline). No p53 mutations were detected in buccal smears or cultured fibroblasts from healthy skin samples of any of the patients. CONCLUSIONS: Focal mutations in p53 may increase cell proliferation and decrease cell death in the dysregulated growth patterns that have been clinically documented. An understanding of the pattern of all growth dysregulation related to keloids may lead to new therapeutic strategies.     

The effects of epidural fentanyl on hemodynamic responses during emergence from isoflurane anesthesia and tracheal extubation: a comparison with intravenous fentanyl

Immune thrombocytopenic purpura (ITP) is a disorder caused by anti-platelet autoantibodies (Ab), most of which are directed against epitopes on platelet membrane glycoprotein complexes GPIIb/IIIa and GPIb/IX. To detect platelet Ab, reliable techniques, such as MAIPA or immunobead assay, have been developed. They all achieve their selective specificity by the use of monoclonal antibodies (MoAb) against defined glycoproteins of the platelet membrane. In order to determine the most frequent Ab-specificities, a novel enzyme-linked immunosorbent assay, named platelet-glycoprotein-ELISA (P-GP-ELISA), has been developed. It uses purified GPIIb/IIIa and GPIb/IX complexes, respectively, as antigens and enables determination of platelet-associated as well as circulating Ab (IgG, IgM). MoAbs are not required and therefore there is no risk of competition between MoAb and Ab. Levels of Ab in patients with the clinical diagnosis of an idiopathic thrombocytopenic purpura were analysed. 92.7% (76/82) platelet eluates with significantly increased levels of Ab against at least one of the glycoproteins were found, whereas no sample from healthy volunteers (0/37) gave a positive result, pointing to a high sensitivity and specificity of the test system. Since its application is also easy and quick, P-GP-ELISA should facilitate detection of Ab against platelet membrane proteins in routine determinations.     

Effects of 5-hydroxytryptamine and bradykinin in cat dorsal horn neurones activated by noxious stimuli

The levels of homovarillic acid and 3,4-dihydroxyphenylacetic acid in rat c. striatum after acute and 10 day administration of clozapine (30 and 100 mg/kg p.o.), thioridazine (100 mg/kg p.o.), haloperidol (1 mg/kg p.o.), and chlorpromazine (30 mg/kg p.o.), were estimated. With clozapine and haloperidol, the mesolimbic area was also investigated. With all these neuroleptics, the levels of both dopamine metabolites were reduced after a 10 day treatment as compared to acute administration, sometimes almost to control values. With clozapine, however, such a reduction occurred only with the higher dose of 100 mg/kg p.o., acting for a period longer than 24 h. This tolerance phenomenon was also observed with clozapine and haloperidol in the mesolimbic area. We conclude that clozapine is not qualitatively different from classical neuroleptics with respect to development of biochemical tolerance.     

Variety of muscle responses to tactile stimuli

Influences exerted by tactile stimuli on the muscle activity were investigated with two methods: (1) analysis of kinematics and electromyographic (EMG) activity of eight forelimb muscles during contact placing (CP) reactions elicited by tactile stimuli applied to the dorsal, medial or lateral sides of the paw in cats, and (2) the Hoffmann (H)-reflex technique to quantify the effects of the tactile stimuli on the excitability of the alpha motoneurones of the soleus muscle in awake rats. The first group of the data showed that the tactile stimuli applied to dorsal, medial or lateral aspects of the paw led to different strategies of the forelimb movements during CP reactions. These differences arose from various patterns of activation of the elbow flexor and extensor muscles at the beginning of CP reactions and a various involvement of the medio-lateral components of movements, depending on the site of the tactile stimulus application. With the H-reflex technique it was found that the tactile stimulus diminished the excitability of alpha motoneurones of the soleus muscle when applied to the skin overlying the lateral side of the ankle joint. This effect was in line with the observation that the tactile stimulus applied to the lateral side of the paw activated the elbow flexor muscles but not their antagonists to initiate CP reaction.     

Isoflurane and sevoflurane augment norepinephrine responses to surgical noxious stimulation in humans

BACKGROUND: Suppression of hypertensive response to noxious stimulation by volatile anesthetics may be a result of suppression of the stimulation-induced norepinephrine response or that of the cardiovascular response to catecholamines, or both. The suppression of the cardiovascular response is established, but that of norepinephrine response has not been confirmed. The authors hypothesized that the suppression of cardiovascular response but not that of norepinephrine response plays a major role in suppressing the noxious stimulation-induced hypertensive response by volatile anesthetics. METHODS: Forty healthy donors for living-related liver transplantation were allocated to four groups: receiving 1.2% (end-tidal) isoflurane in oxygen and nitrogen, 2.0% isoflurane, 1.7% sevoflurane, or 2.8% sevoflurane. The intraoperative plasma norepinephrine and epinephrine concentrations, arterial blood pressure and pulse rate were measured for the first 15 min of surgery and were compared with the preoperative values. RESULTS: Norepinephrine and epinephrine concentrations both increased intraoperatively in all four groups. The values of maximum increase and area under the concentration-versus-time curve of norepinephrine were greater in the high dose groups of both anesthetics. The intraoperative blood pressure did not differ by different doses of anesthetics, and the degree of increase of blood pressure was not proportional to the plasma catecholamine concentrations. CONCLUSION: The effects of isoflurane and sevoflurane on the surgical noxious stimulation-induced norepinephrine response were inversely proportional to the dose. The suppression of noxious stimulation-induced blood pressure response by anesthetics that were studied may be the result of suppression of the responses of vascular smooth muscle and myocardium to catecholamines.     

Upper airway reflexes during a combination of propofol and fentanyl anesthesia

BACKGROUND: The effects of intravenous anesthetics on airway protective reflexes have not been fully explored. The purpose of the present study was to characterize respiratory and laryngeal responses to laryngeal irritation during increasing doses of fentanyl under propofol anesthesia. METHODS: Twenty-two female patients anesthetized with propofol and breathing through the laryngeal mask airway were randomly allocated to three groups: (1) eight patients who received cumulative total doses of 200 microg fentanyl given in the form of two doses of 50 microg and one dose of 100 microg spaced 6 min under mechanical controlled ventilation while end-tidal carbon dioxide tension (PCO2) was maintained at 38 mmHg (fentanyl-controlled ventilation group), (2) eight patients who received cumulative total doses of 200 microg fentanyl while breathing spontaneously while end-tidal PCO2 was allowed to increase spontaneously (fentanyl-spontaneous ventilation group), and (3) six spontaneously breathing patients who were anesthetized with propofol alone (propofol group). The laryngeal mucosa of each patient was stimulated by spraying the cord with distilled water, and the evoked responses were assessed by analyzing the respiratory variables and endoscopic images. RESULTS: Before administration of fentanyl, laryngeal stimulation caused vigorous reflex responses, such as expiration reflex spasmodic panting, cough reflex, and apnea with laryngospasm. Increasing doses of fentanyl reduced the incidences of all these responses, except for apnea with laryngospasm, in a dose-related manner in both the fentanyl-controlled ventilation and the fentanyl-spontaneous ventilation groups. Detailed analysis of endoscopic images revealed several characteristics of laryngeal behavior during the airway reflex responses. CONCLUSION: Incremental doses of fentanyl depress airway reflex responses in a dose-related manner, except for apnea with laryngospasm.     

Approach and avoidance responses of the hysterical personality to sexual stimuli.

Administered a paired-associates learning task and a visual recognition task to 32 female hysterical personalities and 32 nonhysterical personalities. Both tasks included neutral and sexual material. 1/2 the Ss in each group performed under sexually "seductive" conditions, the other 1/2 under neutral conditions. Results showed that (1) hysterics learned sexual material quickly under neutral conditions but relatively slowly under sexual conditions; (2) hysterics had a relatively low visual recognition threshold for sexual words under neutral conditions and a relatively high threshold under sexual conditions; and (3) these threshold differences were maximized when sexual stimuli referred to the self. It was concluded that the characteristic behavior of the hysteric was consistent with an approach-avoidance conflict involving sexual motives and behavior. (19 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Awakening propofol concentration with and without blood-effect site equilibration after short-term and long-term administration of propofol and fentanyl anesthesia

The stage at which breast cancer is diagnosed is an important determinant of prognosis. In contrast to the many investigations of the relationship between alcohol consumption and the risk of developing breast cancer, few have examined how alcohol consumption may affect the stage of this cancer at diagnosis. This article examines the relationship between alcohol intake and breast cancer stage and assesses consumption in relation to the volume of drinks consumed per week and the patterns of consumption 1 year prior to the breast cancer diagnosis. A total of 1191 women, aged 40 to 84 years, with newly diagnosed breast cancer were identified through the population-based Metropolitan Detroit Cancer Surveillance System, a participant of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Of these, 1011 (85%) were interviewed 2 to 4 months following diagnosis. The analyses for this article were limited to 920 cases with local and regional stage disease. The bivariate analysis showed that frequent drinkers were more likely than abstainers or infrequent drinkers to present with regional disease. Logistic regression showed that frequent drinkers were 1.45 times more likely than infrequent drinkers to be diagnosed with later stage breast cancer (95% CI: 1.01-2.10; p = 05). The association between alcohol consumption and disease stage may be due to the relationship between heavy consumption and other unhealthy behaviors. In addition, women who drink more frequently may have less awareness of and access to cancer screening services. Heavy exposure to alcohol may also contribute to accelerated tumor growth once breast cancer is present.     

Modification of unit responses to gustatory stimuli by conditioned taste aversion in rats

Secretion of trypsin, chymotrypsin, lipase and amylase was measured in male rats under urethane anaesthesia using a method of continuous perfusion of the duodenum. Prolonged infusion of cholecystokinin-pancreozymin (CCK-PZ) over a period lasting 200-360 min was administered either alone or together with a submaximal dose of secretin (1 unit/100 g - 10 min). Infusion of CCK-PZ was carried out using maximal doses (1--1.5 unit/100 g - 10 min) with and without secretin. Supramaximal doses of CCK-PZ (2 and 4 units/100 g - 10 min) were used only in combination with secretin. In all experiments secretion of enzymes showed a triphasic pattern including an initial peak followed by a plateau secretion after 10--20 min (phase 1), a decreasing second phase and finally base-line secretion (phase 3), thus demonstrating exhaustion of enzyme output from the gland with time. With increasing and supramaximal dose of CCK-PZ the cumulative output of enzymes from start to baseline secretion decreased progressively. Under the same conditions the levels of peak and plateau secretion were lower, the duration of plateau secretion was longer and the decreasing phase of secretion was shortened. These features indicate inhibition of secretion with increasing supramaximal doses of CCK-PZ infusion. Whereas the proteolytic enzymes and lipase reacted in a parallel way always amylase secretion was sustained on a higher level, implicating an alternative pathway for secretion.     

Habituation of facial muscle responses to repeated food stimuli

The AVE Micro Stent (AVE Inc., Santa Rosa, CA) is composed of helically welded 3 mm long, zigzag crowns with stent lengths from 6 to 39 mm and diameters from 2.5 to 4.5 mm. Quantitative coronary angiography and histologic analyses of acute and chronic implantation were obtained in 52 stented coronary segments of 18 dogs. Three hearts with 8 stented coronary segments were harvested after 24 hr, 3 hearts with 9 stented segments were harvested after 2 weeks, 6 hearts with 15 stented segments were harvested at 8 weeks, and 6 hearts with 20 stented segments were harvested at 24 weeks post-deployment. There were no procedural complications, deaths, or acute vessel closures. The average lumen diameter of the stented segment was largest at 2 weeks (3.3 +/- 0.3 mm). The smallest average diameters were observed at 8 weeks after the stent deployment (2.7 +/- 0.4, P < 0.05) with an increase again at 24 weeks (2.9 +/- 0.6). The pre-explant percent of stenosis was <30% in all animals. Histologically, a peak of inflammation was visible at 2 weeks; however, the extent of luminal narrowing reached its peak at 8 weeks and the lumen dimension increased somewhat at 24 weeks. The degree of intimal thickening remained relatively constant throughout the different time points (<200 microm). Overall, these data suggest that constrictive remodeling within the stented segment occurs at 8 weeks in this animal model. The later increase of the stented segment dimensions as well as higher net gain at 24 weeks compared to 8 weeks after deployment suggests that this constriction is a transitory phenomenon.     

Two time-dependent responses of chicks to imprinting stimuli.

Analyzed in detail the conditions eliciting approach behavior to the imprinting stimulus in White Leghorn, New Hampshire, and hybrid White Leghorn-New Hampshire chicks. It was found that the approach response to a relatively weak imprinting stimulus could arise by 2 different mechanisms. Some Ss approached the stimulus object within a few min.; others needed a considerably longer stimulation, essentially a conditioning, to elicit the approach response. The 2 mechanisms, which were termed "prompt approach" and "conditioned approach," were distinguished on the basis of the different conditions required for eliciting them. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Autonomic and hemodynamic responses to insulin in lean and obese humans

To study the acute effects of insulin on autonomic control of cardiac function, we performed spectral analysis of heart rate variability and measured cardiac dynamics (by two-dimensional echocardiography) in 18 obese (BMI = 35 +/- 1 kg.m-2) and 14 lean (BMI = 24 +/- 1 kg.m-2) subjects in the basal state and in response to physiological hyperinsulinemia (1 mU.min-1.kg-1 insulin clamp). In the lean group, insulin promptly (within 20 min) and consistently depressed spectral powers, both in the low-frequency and high-frequency range. These changes were twice as large as accounted for by the concomitant changes in heart rate (68 +/- 2 to 70 +/- 2 beats/min). At the end of the 2-h clamp, stroke volume (67 +/- 4 to 76 +/- 9 ml.min-1) and cardiac output (4.45 +/- 0.21 to 5.06 +/- 0.55 l.min-1) rose, whereas peripheral vascular resistance fell. The low-to-high frequency ratio increased from 1.7 +/- 0.2 to 2.3 +/- 0.3 (P < 0.01), indicating sympathetic shift of autonomic balance. In the obese group, all basal spectral powers were significantly lower (by 40% on average) than in the lean group, and were further reduced by insulin administration. The low-to-high frequency ratio was higher than in controls at baseline (2.4 +/- 0.4, P < 0.03), and failed to increase after insulin (2.2 +/- 0.3, P = ns). Furthermore, obesity was associated with higher resting stroke volume (89 +/- 5 vs. 67 +/- 4 ml.min-1, P < 0.01) and cardiac output (6.01 +/- 0.31 vs. 4.45 +/- 0.21 l.min-1, P = 0.001) but lower peripheral vascular resistance (15.1 +/- 0.8 vs. 19.2 +/- 1.1 mmHg.min.L-1, P = 0.002), whereas mean arterial blood pressure was similar to control (90 +/- 2 vs. 86 +/- 2 mmHg, P = not significant). We conclude that physiological hyperinsulinemia causes acute desensitization of sinus node activity to both sympathetic and para-sympathetic stimuli, sympathetic shift of autonomic balance, and a high-output, low-resistance hemodynamic state. In the obese, these changes are already present in the basal state, and may therefore be linked with chronic hyperinsulinemia.     

右旋美托咪定减少丙泊酚和芬太尼的用量及对麻醉恢复期的影响

目的:探讨右旋美托咪定(Dex)减少丙泊酚和芬太尼的用量、抑制气管插管和拔管的应激反应以及对麻醉恢复期的影响.方法:选择24例择期手术全麻患者(ASAⅠ～Ⅱ级),将患者随机分成Dex组和对照组,每组各12例.全麻诱导前30 min Dex组以1 μg·kg-1Dex稀释成10 mL、对照组以生理盐水分别静脉泵注10 min.丙泊酚0.4 mg·kg-1·min-1泵注开始诱导,直至患者托下颌无体动时静注芬太尼1 μg·kg-1和爱可松0.6 mg·kg-1,1.5 min后进行气管内插管.插管成功后停丙泊酚吸入七氟醚,Dex组给予Dex 0.3 μg·kg-1·h-1直至手术结束,对照组给予同等容量的生理盐水.手术结束时停用七氟醚,记录患者丙泊酚诱导量和芬太尼总用量,记录患者入室时(T0)、置入喉镜时(T1)、置入气管导管时(T2)、手术后睁眼时(T3)、拔管时(T4)、拔管后10 min(T5)的心率(HR)和平均动脉压(MAP),记录术后呼吸恢复时间、睁眼时间和拔管时间.结果:与对照组比较,Dex组的丙泊酚诱导量(mg·kg-1)减少了21%(P<0.01),芬太尼总用量减少了38%(P<0.01);对照组在T1、T2 、T4的MAP和HR与基础值T0比较明显升高(P<0.01),Dex组T1～T6的MAP、HR与基础值T0比较则无明显变化;Dex组在T1、T2、T4的MAP和HR与对照组比较明显降低(P<0.01).结论:Dex可减少丙泊酚诱导量和术中芬太尼用量,维持气管插管和拔管期间血流动力学稳定,同时对麻醉恢复期没有影响.