Activation of vascular endothelial cells by synovial fibrosis promotes Netrin-1-induced sensory nerve sprouting and exacerbates pain sensitivity

Synovial fibrosis is one of the most dominant histopathological changes in osteoarthritis of the knee (KOA), and activation of vascular endothelial cells in synovial fibrosis is both an important factor in mediating pain in KOA and a major contributor to the generation of pain signals. At the same time, angiogenesis and nerve fibres are more likely to underlie the pathology of pain induced by synovial fibrosis. In the present study, we established a co-culture model of human umbilical vein endothelial cells (HUVECs) with dorsal root ganglion (DRG) and detected tissue and cellular Netrin-1, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), growth-associated protein-43 (GAP43), colorectal cancer deleted (DCC), uncoordinated 5 (UNC5), and the related expression of calcitonin gene-related peptide (CGRP), substance P (SP) and nerve growth factor (NGF) in supernatant by ELISA to investigate the intervention of vascular endothelial cell activation on sensory nerve sprouting exacerbating peripheral pain sensitivity and to investigate the effect of Netrin-1 from the perspective of Netrin-1 secretion to illustrate its effector mechanism.     

Primary defect of juvenile visceral steatosis (jvs) mouse with systemic carnitine deficiency is probably in renal carnitine transport system

We investigated the reabsorptional system for carnitine in the kidney to elucidate the mechanism of carnitine deficiency in juvenile visceral steatosis (jvs) mice. Jvs mice had a higher rate of carnitine excretion at 10 days after birth than the controls, in spite of having no pathological acylcarnitine in the urine. In an experiment to assay the uptake of carnitine using kidney slices, homozygous mutants showed significantly lower rates of Na-dependent carnitine uptake than controls. Heterozygous mice showed values of transport activity intermediate between homozygous mutants and homozygous controls. Scatchard plots (transport activity versus transport activity/carnitine concentration) revealed that the homozygous mutants had a defect in the hihg affinity site (K_m = 58 μM) in the Na-dependent carnitine transport system in the kidney. These results indicate that the primary defect of jvs mice is most probably related to the system for reabsorption of carnitine in the kidney.     

The effect of prolonged isometric contractions on muscle fluid balance

Ultrasound scanning was performed at three sites above the fossa supraspinata on nine healthy subjects and five patients with myofascial shoulder pain. This method produced a well-defined depiction of the soft tissue layers above the fossa supraspinata and reproducible muscle thickness measurements. In the healthy subjects the average distance from the skin surface to the trapezius muscle was 7.7 mm and the average thickness of the trapezius muscle was 5.3 mm, and the average thickness of supraspinatus muscle was 20.0 mm. The supraspinatus muscle was thinner at the medial measuring site than at the other two sites. In contrast, a tendency towards a larger distance was seen from the skin to trapezius muscle at the medial measuring site than at the other two sites. No statistical differences were found between the two groups of subjects either at rest or during brief shoulder abductions. All the subjects performed a 30° unilateral isometric shoulder abduction test to exhaustion. The median endurance time was 33 min for the healthy subjects and only 5 min for the patients. The ratings of perceived exertion (RPE) were in line with this, since the increment in RPE with time was larger for the patients than for the healthy group. The reduced shoulder abduction endurance time in the patient group may have been related to impaired muscle function and/or pain development. During the 33-min shoulder abduction in the healthy subjects, the thickness of supraspinatus muscle increased by 14%, indicating muscle swelling, whereas the thickness of trapezius muscle remained constant. The fluid imbalance in the supraspinatus muscle compartment may well play a role in the development of muscle fatigue and the disorders found in industry resulting from prolonged work with arms elevated.     

Elevated Nerve Growth Factor Levels in the Synovial Fluid of Patients with Inflammatory Joint Disease

A novel pH shock extraction procedure was used to measure nerve growth factor (NGF) levels in both normal and inflamed synovial fluids using a sensitive and specific two-site enzyme linked immunosorbant assay. To date no data is available on NGF levels in normal synovial fluids. Synovial fluids were taken from 5 normal volunteers, 12 patients with rheumatoid arthritis and 10 patients with other inflammatory arthropathies. The mean ± SEM NGF concentration in normal synovial fluids was 95 ± 33.2 pg/ml (range 39.1–143.1 pg/ml), whereas the mean NGF concentration in the synovial fluids taken from patients with rheumatoid arthritis was 532.5 ± 123.8 pg/ml (range 152–1686 pg/ml). The mean NGF concentration in patients with other inflammatory arthropathies was also raised (430.6 ± 90 pg/ml; range 89–1071 pg/ml). The NGF concentrations were significantly higher in the synovial fluids from both inflamed groups (ANOVA p < 0.05) compared to normals. Raised levels of NGF in synovial fluid may contribute directly to joint inflammation via activation of inflammatory cells.     

电针对大鼠尾核痛兴奋,痛抑制神经元放电和甩尾反射的影响

浅麻醉ｗｉｓｔａｒ大鼠２５只,用Ｇ－６８０５型治疗仪电针刺激双侧“足三里”。以辐射热照尾部作为伤害性刺激,将痛兴奋神经元（ＰＥＮ）诱发放电频率减少,痛抑制神经元（ＰＩＮ）诱发放电频率增加和甩尾反射潜伏期（ＴＦＬ）延长作为镇痛效应,观察电针刺激“足三里”对尾核中ＰＥＮ、ＰＩＮ及ＴＦＬ的影响。结果表明,电针刺激“足三里”,尾核中ＰＥＮ、ＰＩＮ放电及ＴＦＬ均显示镇痛效应;电针对ＰＥＮ、ＰＩＮ放电及ＴＦＬ的影响高峰均出现在电针后即刻;电针前ＰＥＮ放电频率增加、ＰＩＮ放电频率减少与甩尾反射（ＴＦ）相伴行。放电变化发生在ＴＦ之前,结束在ＴＦ之后,ＰＥＮ、ＰＩＮ放电变化与ＴＦＬ呈高度正相关。镇痛作用高峰期ＰＥＮ、ＰＩＮ放电变化仍在ＴＦ前,结束在ＴＦ之后,两者呈高度正相关。提示尾核中的ＰＥＮ、ＰＩＮ是痛觉调节中枢的一部分,可能参与对ＴＦ的调节。     

Reduction in the mechanonociceptive response by intrathecal administration of glycine and related compounds

We have previously reported that enhanced glycine release is produced by epidural spinal cord stimulation, a clinical method for treating neuropathic pain. Our current hypothesis is that glycine administered intrathecally reduces neuropathic pain as measured by the Randall-Selitto method. Neuropathic rats created by unilateral partial ligation of the sciatic nerve were treated with intrathecal infusion of glycine, strychnine, MK-801, or 5,7-DKA at 0.1 μmol, or artificial CSF for 2 hours at a rate of 10 μl/min. Force required to produce the pain response was significantly increased after glycine administration and reduced using strychnine, a specific glycine receptor (Gly 1) antagonist. Strychnine blocked the response to glycine when infused together. Administration of the non-specific NMDA receptor MK-801 antagonist and 5,7-DKA, a specific glycine-NMDA receptor (Gly 2) antagonist, however, failed to block the response to glycine. Our results provide evidence for the use of glycine and related compounds to treat neuropathic pain.     

链脲佐菌素糖尿病大鼠尾神经中传入单位的反应特性

实验观察了链脲佐菌素糖尿病大鼠尾神经中各种传入单位的反应特性,发现糖尿病大鼠的部分Ｃ单位和Ａδ单位具有自发放电,它们的机械阈值显著降低。糖尿病大鼠的Ｃ单位对持续１ｍｉｎ的机械性阈刺激的反应同对照组相似,而在阈上机械性刺激期间呈增频效应,撤除阈刺激和阈上刺激后后放电均明显增多。除Ｃ单位、Ａδ单位外,Ａβ机械感受性单位的传导速度也明显减慢,但在Ｃ单位、Ａδ单位和Ａβ机械感受性单位中,各种亚单位的比例同对照组相比无显著性差异。结果表明,糖尿病大鼠Ｃ单位和Ａδ单位机械阈值的降低有助于其行为伤害性阈值的下降,Ｃ单位和Ａδ单位的异常电活动是糖尿病大鼠产生对痛刺激敏感性升高和感觉异常的外周因素。     

Biofeedback-assisted relaxation training for the aging chronic pain patient

The older segments of the U.S. population are expanding rapidly and account for a disproportionate amount of health care, including treatment for pain-related musculoskeletal disorders. In a prospective study with objective measures and one-year follow-up, Middaugh et al. (1988) found that older patients (55–78 yr; N=17, 76% success) treated in a multidisciplinary chronic pain rehabilitation program enjoyed a success rate equal to that of younger patients (29–48 yr; N=20, 70% success). The current study presents additional data on these two groups of patients to compare their ability to learn the physiological self-regulation skills taught in the biofeedback/relaxation component of the multimodal program. This component included progressive muscle relaxation training, diaphragmatic breathing instruction, and EMG biofeedback. Repeated measures ANOVA showed significant increases in digital skin temperature (peripheral vasodilation) and decreases in respiration rate both within and across training sessions (p values=.04 to .0001) with no differences between age groups (p>.05). EMG measures for the upper trapezius ms in patients with cervical pain showed similar deficits in muscle control at evaluation and similar improvements with biofeedback training for the two age groups. These findings indicate that older pain patients responded well to the biofeedback/relaxation training component of the multimodal pain program.This research was supported in part by NIDRR grant No. H133G90085, Department of Education, DHEW, and by the Medical University of South Carolina General Clinical Research Center under NIH grant No. RR1070.     

一足致炎大鼠双足伤害感受性的变化

大鼠一侧鹿角菜致炎足痛阈显著降低后,对侧非致炎足的痛阈出现显著降低、不变,和显著升高等变化。对侧非致炎足痛阈的这三种变化与致炎足痛阈降低幅度的大小显著相关。     

Leishmania donovani: action of excreted factor on hydrolytic enzyme activity of macrophages from mice with genetically different resistance to infection

The effect of purified excreted factor from promastigotes of Leishmania donovani upon the activity of four enzymes from lysed peritoneal exudate cells of mice (C3H and C57BL) was determined. There was no demonstrable effect on acid phosphatase (EC3.1.3.2), β-glucuronidase (EC3.2.1.21), and N-acetyl-β-glucosaminidase (EC3.2.1.29), but β-galactosidase (EC3.2.1.23) was inhibited up to 72% after 3 hr of incubation at 37 C. Inhibition of C57BL mouse enzymes was not significantly different from that of C3H mice. Protamine sulfate combined with the highly negatively charged excreted factor of L. donovani to migrate as a single positively charged band on immunoelectrophoresis. Protamine sulfate also reversed the β-galactosidase inhibition, though this was without direct effect on the enzyme. The excreted factor did not change or lose its charge or antigenicity with regard to precipitating antibody, when incubated with extracts of mouse peritoneal exudate cells, splenocytes, or liver homogenate—irregardless of whether the mice had been infected with leishmaniasis for 1 or 2 weeks or were uninfected.