Search PubMed⌕ Search

Biomedical subjects

T Masuyama

Publications and source records attributed to T Masuyama.

At least 19 recordsLinked to original sources

Quantitative ultrasonic tissue characterization can identify high-risk atherosclerotic alteration in human carotid arteries.

BACKGROUND: Recently, ultrasonic tissue characterization of the composition of plaques has been performed in a quantitative fashion on the basis of integrated backscatter (IBS) analysis, but most of those studies have used high-frequency ultrasound to obtain microscopic images. METHODS AND RESULTS: We performed B-mode measurement and IBS signal analysis with acoustic densitometry with a 7.5-MHz linear-array transducer in freshly excised human aortas (n=58) (normal, atheromatous, and fibrous tissue) obtained at autopsy. Atheromatous and fibrous tissue had a similar intima-media thickness (IMT), but the IBS value in atheromatous specimens was lower than that in fibrous specimens. We further applied this method to human carotid ultrasonography. The subjects were young (80 regions), middle aged with 1 or no coronary risk factors (low risk) (120 regions), middle aged with >/=2 coronary risk factors (high risk) (240 regions), or elderly (80 regions) or were patients with myocardial infarction (MI) with multivessel disease (90 regions). The IMT was similar in middle-aged, elderly, and MI subjects. In contrast, the IBS value was significantly higher in elderly subjects and lower in high-risk middle-aged and MI subjects compared with that in low-risk middle-aged subjects. The percent of regions diagnosed as atheromatous (IBS less than mean minus 2-SD value of IBS in young subjects) was 11% in low-risk middle-aged subjects, 29% in high-risk middle-aged subjects, and 63% in the MI group. CONCLUSIONS: In conjunction with conventional B-mode imaging, IBS analysis with carotid ultrasonography appeared to provide prognostic information to identify a high-risk group with systemic atherosclerosis, which could lead to coronary heart disease in individuals with early-stage disease.

Adult↗

Local neurohumoral regulation in the transition to isolated diastolic heart failure in hypertensive heart disease: absence of AT1 receptor downregulation and 'overdrive' of the endothelin system.

OBJECTIVE: Although isolated diastolic heart failure with preserved left ventricular (LV) systolic function frequently occurs, regulation of local neurohumoral factors in the transition from diastolic dysfunction without signs of heart failure to diastolic failure, a target for therapeutic strategy, remains to be clarified, partly because of a lack of animal models. Our laboratory recently demonstrated that Dahl-Iwai salt-sensitive (Dahl-S) rats fed on a high-salt diet since 7 weeks of age develop hypertension followed by compensated LV hypertrophy at 13 weeks and transition to isolated diastolic heart failure at 19 weeks. METHODS: Gene expression of the components of the renin-angiotensin system, endothelin (ET) system and natriuretic peptide system in the left ventricle was investigated in the transition to isolated diastolic heart failure in this model. RESULTS: The compensated ventricular hypertrophy was associated with slight increases in angiotensin-converting enzyme (ACE) and angiotensin II type-1a (AT1a) receptor mRNA levels. Although preproET-1 (ppET-1) and ET-converting enzyme-1 (ECE-1) mRNA levels were not increased, mRNA levels of ET type-A (ETA) and ET type-B (ETB) receptors were increased. Atrial natriuretic peptide (ANP) mRNA level increased, but not brain natriuretic peptide (BNP) mRNA level. At the decompensated failing stage (at 19 weeks), ACE mRNA level further increased without downregulation of ATla receptor mRNA level. The mRNA levels of ppET-1 and ECE-1 increased with persistent upregulation of mRNA levels of ETA and ETB receptors, and immunohistochemical staining for ET-1 was found at endothelial cells and myocytes. BNP mRNA level increased with a further increase in ANP mRNA level. CONCLUSIONS: The transition to isolated diastolic heart failure in hypertrophied hearts was associated with preserved gene expression of the renin-angiotensin system and 'overdrive' of gene expression of the ET system. BNP gene expression is likely to be activated by the progression of diastolic failure rather than by LV hypertrophy alone.

Analysis of Variance↗

Roles of renin-angiotensin and endothelin systems in development of diastolic heart failure in hypertensive hearts.

OBJECTIVE: Although interest in diastolic heart failure is growing because of its clinical frequency, little is known about this type of heart failure. Our laboratory recently developed a diastolic heart failure model using Dahl salt-sensitive rat. In this model, gene expression of angiotensin-converting enzyme and endothelin (ET) system in the left ventricle was enhanced at heart failure stage without downregulation of angiotensin type 1a receptor mRNA level. However, the roles of these humoral systems in the transition to diastolic failure remain unclear. METHODS: Subdepressor doses of angiotensin II type 1 (AT1) receptor and ET type A (ETA) receptor antagonists were administered in this model just after onset of hypertension, and their effects were investigated. RESULTS: Neither AT1 nor ETA receptor blockade inhibited the early (13 weeks) compensatory left ventricular (LV) hypertrophy. This form of compensatory hypertrophy is associated with subnormal LV end-systolic stress, which was normalized by AT1 receptor blockade but not by ETA receptor blockade. Progression of LV hypertrophy and fibrosis and transition to heart failure (19 weeks) in the untreated rats were prevented by both antagonists, resulting in normalization of LV end-diastolic pressure and lung weight. AT1 receptor blockade, but not ETA receptor blockade, normalized time constant of LV relaxation. Enhanced gene expression for ET system in the left ventricle observed in the untreated rats was suppressed with AT1 receptor antagonist administration. ETA receptor blockade slightly but significantly elevated the AT1a receptor mRNA level as compared with the untreated rats. CONCLUSIONS: RAS and ET system contribute to the transition to diastolic heart failure through the development of excessive hypertrophy and ventricular fibrosis in hypertensive heart diseases, however, neither RAS nor ET system is mandatory for normal compensation for pressure overload. RAS apparently causes such diastolic effects at least partly through the ET system.

Angiotensin Receptor Antagonists↗

Effect of pre-reperfusion residual flow on recovery from myocardial stunning: a myocardial contrast echocardiography study.

BACKGROUND: Myocardial contrast echocardiography (MCE) may be used to assess coronary microvasculature in patients with myocardial infarction. Myocardial contrast echocardiography-no reflow suggests poor functional outcome; however, MCE with reflow does not necessarily indicate good myocardial salvage or sufficient functional recovery from myocardial stunning. In this study, MCE was performed to assess the effect of pre-reperfusion residual flow (PRF) on the recovery from myocardial stunning. METHODS AND RESULTS: The size of the occluded bed, an area supplied with an infarct-related artery, was determined by comparing pre- and post-reperfusion MCE images in 40 patients with first acute myocardial infarction. Myocardial contrast echocardiography-no reflow was observed after reperfusion in 8 patients. Significant PRF was not recognizable in any of the 8 patients. The other patients with MCE reflow were subdivided into 2 groups on the basis of the ratio of the area perfused by PRF to that of the occluded bed: 14 patients with the ratio of more than 10% (PRF[+]), and the other 18 patients (PRF[-]). The wall motion score (0, normal to 4, dyskinetic) was obtained in the convalescent stage. RESULTS: (1) Wall motion of the infarct area after day 3 was better in patients with PRF than in patients without PRF. (2) Left ventricular functional improvement in the long term was remarkable in patients with good reflow and PRF(+), modest in patients with good reflow but PRF(-), and not detectable in patients with MCE-no reflow. No significant correlation was found between angiographic collateral grades and PRF. CONCLUSIONS: The presence of residual flow within the infarct area before reperfusion results in not only good myocardial salvage but also rapid functional recovery from myocardial stunning.

Coronary Circulation↗

High-frame-rate tissue harmonic imaging enhances anatomic M-mode sections of the left ventricle in short-axis view.

BACKGROUND: High-frame-rate echocardiography (HFRE) and tissue harmonic imaging (THI) may improve image quality, thereby enabling anatomic M-mode sections of left ventricular (LV) wall segments to be visualized in various planes in the short-axis view. OBJECTIVES: The goals of this study were to compare image quality between HFRE and conventional-frame-rate echocardiography (CFRE) and between fundamental imaging (FI) and THI, and to obtain anatomic M-mode values of basal short-axis LV segments from healthy subjects for use in the evaluation of abnormal segments in patients with myocardial infarction (MI). METHODS AND RESULTS: The study included 28 healthy subjects and 15 patients with MI who underwent 2-dimensional echocardiography with an ultrasonographic system equipped with THI and anatomic M-mode. Left ventricular image cineloops at the basal short-axis view that were obtained with 3 combinations of imaging techniques (FI + CFRE, FI + HFRE, and THI + HFRE) were digitized and displayed side-by-side in random order for comparison by blinded readers. M-mode sections were done in 3 planes: anteroseptal-posterior, inferoseptal-lateral, and anterior-inferior basal segments. The THI + HFRE combination showed the best image quality with significant reduction in noise artifacts, resulting in a good signal-to-noise ratio and good tractability of all LV segments by anatomic M-mode. In healthy subjects, significant intersegmental differences existed in the diastolic and systolic thicknesses and in the percent systolic thickening of LV segments. In patients with MI, LV systolic thickening was significantly decreased in abnormal segments. No significant differences were noted in ejection fraction and fractional shortening among the 3 anatomic M-mode planes. CONCLUSION: High-frame-rate tissue harmonic imaging improved image quality, thereby allowing reproducible anatomic M-mode measurements in various planes in the short-axis view and providing a convenient objective evaluation of global and regional LV function.

Adult↗

Myocardial longitudinal motion by tissue velocity imaging in the evaluation of patients with myocardial infarction.

Left ventricular (LV) longitudinal shortening plays an important role in cardiac contraction and is invariably affected by the presence of coronary artery disease. Third-generation tissue velocity imaging (TVI) color-maps cardiac movement by obtaining mean velocities of LV segments from the same set of beats. The goals of this study were to characterize patterns of longitudinal myocardial motion velocity in healthy subjects and to use these patterns to evaluate abnormal segments of patients with myocardial infarction (MI). Included were 20 healthy subjects and 16 patients with MI who underwent a 2-dimensional Doppler echocardiography study. Myocardial velocity profiles were taken at the anulus, basal, mid, and apical segments of the septal and lateral walls in the apical view. Segmental velocity patterns from healthy subjects were compared with abnormal segments in patients with MI. Both lateral and septal walls of healthy subjects showed significant basal-apical myocardial velocity reductions in systolic shortening (Sm) and early and late diastolic lengthening (Em and Am) and a basal-apical increase in the Em/Am ratio. The lateral wall had greater Sm and Em velocities than the septal wall. The Sm and Em velocities and the Em/Am ratio were significantly reduced in the abnormal segments in patients with MI. Latent lateral wall ischemia may have been detected in 5 of 9 patients with septal infarction, showing reduced Sm velocity in apparently normal lateral walls. In conclusion, TVI objectively quantifies directional and incremental changes in myocardial movement that are useful in evaluating global and regional myocardial function, and it may play a role in the detection of early myocardial ischemia.

Adult↗

Development of different phenotypes of hypertensive heart failure: systolic versus diastolic failure in Dahl salt-sensitive rats.

OBJECTIVE: There are two phenotypes of heart failure, systolic failure and isolated diastolic heart failure with preserved left ventricular systolic function. Although isolated diastolic heart failure frequently occurs, there are only models for diastolic dysfunction unassociated with heart failure and models with overt diastolic heart failure have not been established. We attempted to develop two different models, i.e. diastolic and systolic failure models, based on hypertension. MATERIALS AND METHODS: Dahl salt-sensitive rats were placed on 8% NaCl diet from 7 weeks old (7-week starting group) or 8 weeks old (8-week starting group). As an age-matched control, Dahl salt-sensitive rats were consistently placed on normal chow. In these rats, echocardiogram was serially recorded, followed by hemodynamic and histological studies. RESULTS: The 7-week starting rats showed a steep elevation in blood pressure and progressive left ventricular hypertrophy, and fell into overt heart failure at approximately 19 weeks. The development of heart failure was not associated with a decrease in left ventricular midwall fractional shortening or an increase in left ventricular end-diastolic dimension as compared with the age-matched control, which mimics the characteristics of clinically observed isolated diastolic heart failure. The 8-week starting rats showed a gradual rise in blood pressure and less progressive left ventricular hypertrophy, and fell into heart failure at approximately 26 weeks with a decrease in mid-wall fractional shortening and an increase in left ventricular end-diastolic dimension. Hemodynamic and histological studies at failing stage revealed comparable elevation of left ventricular end-diastolic pressure and comparable left ventricular fibrosis in both groups. CONCLUSION: These two different models of overt heart failure may be useful as models of isolated diastolic heart failure and systolic heart failure based on the same hypertensive heart disease, respectively, and may contribute to discrimination of the mechanisms of the development of the two different phenotypes of heart failure.

Animals↗

[Clinical implications of ultrasonic tissue characterization for atherosclerotic carotid intima-media].

Current imaging modalities, such as ultrasonic tissue characterization, have enabled accurate determination of the composition of atherosclerotic plaque of excised aortic tissue. The aim of this study is to compare integrated backscatter (IBS) echo signals of the intima-media complex of human carotid arteries between young and elderly subjects, and to evaluate the ability of ultrasonic tissue characterization. We compared the difference in ultrasonic parameters between the carotid arteries of young healthy subjects (n = 27, 25 +/- 1 y.o.) and elderly subjects (n = 55, 75 +/- 4 y.o.). Intima-media thickness (IMT) and calibrated IBS value (C-IBS: Tissue IBS-vessel lumen IBS value) were measured. The IMT values of young and elderly subjects were 0.54 +/- 0.03 and 1.08 +/- 0.07 mm, respectively (p < 0.01). C-IBS of elderly subjects (11.7 +/- 0.8 dB) was significantly higher than that of young subjects (6.9 +/- 0.7 dB). Significantly wider standard deviation of C-IBS value in each individual was observed in elderly subjects (mean +/- SE of individual standard deviation in C-IBS: 4.2 +/- 0.9 dB) compared with that in young subjects (1.7 +/- 0.3 dB). This might reflect varied composition of atherosclerotic plaques in elderly subjects. IBS analysis would become a promising method to distinguish plaque composition quantitatively and to assess the stability of plaques in clinical setting.

Adult↗

[Intravenous contrast echocardiography].

Intravenous contrast echocardiography has become possible in Japan because of the release of the commercially available contrast agent, Levovist. Intravenous administration of Levovist satisfactorily stains the left ventricular cavity, which makes it possible to clearly delineate the endocardial border. Clear delineation of the endocardial border provides easy and accurate measurement of left ventricular dimension and wall thickness, and wall motion abnormalities can be easily and accurately judged, too. Another benefit of intravenous contrast echocardiography is the assessment of myocardial perfusion. Our preliminary experimental and clinical experiences showed the possibility of myocardial staining with intravenous contrast echocardiography. Impressive myocardial staining is obtainable with the combined use of intermittent and contrast harmonic power Doppler imaging. In order to obtain reproducible and clear myocardial contrast images, we have to pay attention to how to inject contrast and settings of ultrasound equipment, i.e., mechanical index, gain setting, depth of focus point, and pulse repetition frequency, artifacts. In the near future, a lot of issues should be standardized to make it possible to compare myocardial contrast echo studies.

Contrast Media↗

Early temporal changes in coronary flow velocity patterns in patients with acute myocardial infarction demonstrating the "no-reflow" phenomenon.

Coronary flow velocity pattern in patients with acute myocardial infarction demonstrating no-reflow phenomenon is characterized with early systolic retrograde flow and rapid deceleration of diastolic flow velocity. In this study, we investigated the early temporal changes in microvascular function in patients with the no-reflow phenomenon. Among 144 patients with a first acute myocardial infarction, 33 exhibited sizable no-reflow phenomenon after coronary reperfusion with myocardial contrast echocardiography. We assessed temporal changes in coronary flow velocity patterns with the Doppler guidewire. The early systolic retrograde flow was observed < or = 10 seconds after reperfusion in 16 patients (group A) or later in 17 patients (331 +/- 327 seconds, group B). Diastolic deceleration rate was higher in group A than in group B at 1 minute after reperfusion. It gradually increased in group B and showed comparable value to group A 10 minutes later. Group A had longer elapsed time from symptom onset to reperfusion and a greater number of infarct Q waves before reperfusion than group B (14 +/- 13 vs 5 +/- 2 hours, p <0.01; and 3 +/- 2 vs 2 +/- 1, p <0.02). In contrast, the incidence of transient ST reelevation shortly after reperfusion was higher in group B (76% vs 25%, p <0.01). Thus, the characteristic coronary flow velocity pattern is either established at the moment of coronary reperfusion or progresses thereafter in patients with no-reflow phenomenon. This suggests different mechanisms of developing ischemic microvascular injury.

Adult↗

Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction.

OBJECTIVES: We assessed whether the intravenous administration of nicorandil, an adenosine triphosphate (ATP)-sensitive K+ channel opener, exerts beneficial effect on microvascular function and functional and clinical outcomes in patients with acute myocardial infarction (AMI). BACKGROUND: Experimental studies documented that ATP-sensitive K+ channel opener exerts cardioprotection after prolonged ischemia. METHODS: We randomly divided 81 patients with a first anterior AMI into two groups, nicorandil (n = 40) and control groups (n = 41). All patients received successful coronary angioplasty within 12 h after the symptom onset and underwent myocardial contrast echcardiography (MCE) with the intracoronary injection of sonicated microbubbles. In the nicorandil group, we injected 4 mg of nicorandil followed by the infusion at 6 mg/h for 24 h and by oral nicorandil (15 mg/day). RESULTS: The improvement in regional left ventricular function, wall motion score and regional wall motion was significantly better in the nicorandil group then in the control group. Intractable congestive heart failure, malignant ventricular arrhythmia and pericardial effusion were more frequently found in the control group than in the nicorandil group (15% vs. 37%, 5% vs. 20% and 8% vs. 37%, p < 0.05, respectively). The frequency of sizable MCE no reflow phenomenon was significantly lower in the nicorandil group than in the control group (15% vs. 33%, p < 0.05). CONCLUSIONS: Intravenous nicorandil in conjunction with coronary angioplasty is associated with better functional and clinical outcomes compared to angioplasty alone in patients with an anterior AMI. Myocardial contrast echocardiography findings imply that an improvement in microvascular function with nicorandil may be attributable to this better outcome.

Angioplasty, Balloon, Coronary↗

Ultrasonic tissue characterization predicts myocardial viability in early stage of reperfused acute myocardial infarction.

BACKGROUND: The aim of the present study was to characterize temporal changes in cyclic variation of ultrasonic integrated backscatter (IBS), which reflects intrinsic contractile performance, in patients with reperfused acute myocardial infarction (AMI) and to elucidate the clinical value of tissue characterization in predicting myocardial viability. METHODS AND RESULTS: We recorded short-axis IBS images before and 3, 7, and 21 days after reperfusion in 26 patients with AMI and obtained the cyclic variation of IBS in the normal and infarct zones. When cyclic variation showed synchrony and asynchrony, we expressed its magnitude as positive and negative values, respectively, called the phase-corrected magnitude. We also measured average wall motion score (dyskinesis, 4; normal, 0) of the infarct segments. The phase-corrected magnitude was lower in the infarct zone than in the normal zone before reperfusion (0.3+/-2.5 versus 5.2+/-1.7 dB, P<.05). At day 3, the phase-corrected magnitude increased by 2.1+/-2.6 dB despite no improvement in wall motion. Improvement in wall motion was observed only at day 21. The patients with the phase-corrected magnitude of > or =2.0 dB at day 3 showed significantly lower wall motion score at day 21 than did the other patients (1.7+/-0.6 versus 2.4+/-0.5, P<.01). CONCLUSIONS: In patients with AMI, cyclic variation of IBS is blunted during ischemia but recovers much faster after reperfusion than the improvement in wall motion. The greater phase-corrected magnitude at day 3 may be a predictor of better functional improvement.

Adult↗

[Intrapulmonary arterial injection of Albunex for left heart contrast echocardiography].

Contrast enhancement of the left heart cavity and myocardium were assessed after venous injection of the ultrasound contrast agent Albunex. Myocardial perfusion was also assessed using a drug stress and image analyzing system. The study population consisted of 46 patients with normal cardiac function and without coronary artery disease, and 38 patients with effort angina. Contrast echocardiography was performed by imaging the parasternal or apical long-axis view during pulmonary arterial injection of Albunex through a Swan-Ganz catheter. Contrast enhancement in the left ventricular cavity and ascending aorta were visually assessed. Hemodynamic, arterial blood gas and electrocardiography changes were recorded before and after the injection of Albunex. Contrast echocardiography was performed before and during intravenous infusion of dipyridamole to assess left ventricular myocardial enhancement by both visual inspection and peak background-subtracted gray level using an image analyzing system. Doppler flow signal change after the injection of Albunex was assessed in 26 patients using a Doppler guide wire located in the left anterior descending coronary artery. Good contrast enhancement was obtained in all patients in the left ventricular cavity and in 17% of patients in the ascending aorta. No significant changes were observed in hemodynamics, electrocardiograms and aortic gas analysis. Significant myocardial enhancement was not seen in any patient but gray level analysis of the echo images during dipyridamole infusion showed significant enhancement in 25% of the patients without coronary artery disease and in 34% of the patients with effort angina. Doppler flow signal in the coronary artery was significantly augmented in all patients after injection of Albunex and suggests that ultrasound contrast agent reaches coronary arteries in all patients regardless of myocardial contrast enhancement. Contrast echocardiography with pulmonary arterial injection of Albunex is safe and useful to obtain sufficient left ventricular contrast enhancement. For myocardial perfusion assessment, further refinement of the ultrasound contrast agent and echo equipment is necessary.

Adult↗

[Contrast enhancement using the triggered imaging].

Triggered imaging has been introduced as a practical method to improve contrast echo enhancement by T.R. Porter, Nebraska, U.S.A. in 1995. It requires a simple instrumentation, ECG or internal timer, for intermittent ultrasound imaging that reduces contrast attenuation due to ultrasound exposure. Currently, a clear myocardial contrast echo done by intravenous injection of contrast agent has become a common result when the latest generation agents, machines and the new methods are available. Contrast echocardiography is expected to be able to evaluate myocardial perfusion for future direction.

Animals↗

Beneficial effect of intracoronary verapamil on microvascular and myocardial salvage in patients with acute myocardial infarction.

OBJECTIVES: We assessed the acute effect of intracoronary injection of verapamil on microvascular function after primary percutaneous translumanal coronary angioplasty (PTCA) for acute myocardial infarction (AMI) with myocardial contrast echocardiography (MCE) in relation to functional outcomes. BACKGROUND: Recent clinical studies have documented the potential of verapamil for possible increase in coronary blood flow after primary PTCA. METHODS: Forty patients with a first AMI were randomly assigned to the verapamil group (n = 20) or the control group (n = 20). In the verapamil group, verapamil (0.5 mg) was injected into the infarct-related artery shortly after PTCA, followed by the oral administration. We performed MCE with an intracoronary injection of sonicated microbubbles before and after verapamil. To assess microvascular integrity, we determined the baseline-subtracted peak intensity in the risk area and the ratio of the no reflow zone plus the low reflow zone to the risk area (low reflow ratio). We determined the average wall motion score (dyskinesia/akinesia = 3; normal = 0) in the risk area on the day of AMI and a mean of 24 days later. RESULTS: The low reflow zone was observed shortly after PTCA in 14 verapamil group patients, and the low reflow ratio decreased after verapamil (0.39 +/- 0.23 vs. 0.29 +/- 0.17 [mean +/- SD], p < 0.05). Peak intensity significantly (p < 0.05) increased from 6 +/- 5 to 12 +/- 6 after verapamil. The reduction in wall motion score from the acute (day -1) to the late stage (day -24) was significantly greater in the verapamil group than in the control group (0.7 +/- 0.8 vs. 0.2 +/- 1.3, respectively, p < 0.05). CONCLUSIONS: Intracoronary administration of verapamil after primary PTCA can attenuate microvascular dysfunction and thereby augment myocardial blood flow in patients with AMI, leading to better functional outcome than with PTCA alone.

Adult↗

Antinociceptive involvement of substance P in the spinal cord of mice: dose effects of substance P on the behavior elicited by intrathecally administered NMDA.

The functional interaction between substance P (SP) and N-methyl-D-aspartate (NMDA) was studied to clarify the diversity of the roles of SP in nociceptive processes at the spinal level in mice. Behavioral responses elicited by intrathecal co-administration of NMDA (0.25 nmol) with various doses of SP (0.3-12 pmol) were observed for 1 min. The high dose of SP (12 pmol) potentiated NMDA-induced responses, which consisted of caudally directed licking and biting, while the low dose of SP (1 pmol) significantly reduced the responses by 40% compared to control mice administered NMDA alone. The antinociceptive effect of the low dose of SP was negated by co-administration of the opioid receptor antagonist naloxone. Furthermore, the antinociception produced by SP was present in mice pre-treated with systemic administration of capsaicin during the neonatal period. These results suggest that one of the roles SP plays at the spinal level is an involvement in antinociception. The activities of excitatory dorsal horn neurons are considered to be inhibited by endogenous opioid peptides released from inhibitory dorsal horn neurons directly stimulated by SP.

Animals↗