endothelin-1 and Peripheral-Nervous-System-Diseases

To explore the efficacy and mechanism of hemoperfusion (HP) plus hemodialysis (HD) for peripheral neuropathy of uremic patients on maintenance hemodialysis.. A total of 66 uremic patients on hemodialysis during January 2014 and April 2011 were assigned randomly into HP+HD, low-flux HD and high-flux HD groups (n=22 each). The serum levels of leptin, endothelin-1 (ET-1), parathyroid hormone (PTH) and β-2 microglobulin were observed pre and post-treatment. And sensory conduction velocity (SCV) was detected simultaneously.. After 12-week treatment, the clinical symptoms of group HP+HD improved significantly with an effective rate of 90.91% while improvement was not obvious in groups high-flux and low-flux HD with effective rates of 31.82% and 13.64%. In HP+HD group, the levels of leptin, ET-1, PTH and β-2MG decreased, sensory conduction velocity increased (P<0.05) and clinical symptoms improved apparently. While in low-flux HD and high-flux HD groups, leptin, ET-1, PTH and β-2MG had no decrease and SCV showed no improvement (P>0.05). Correlation analysis showed that the levels of leptin, ET-1 and β-2MG were negatively correlated with SCV (r=-0.57, r=-0.47, r=-0.56). Yet PTH had no correlation with SCV (r=-0.23).. Hemoperfusion plus hemodialysis may improve the clinical symptoms of peripheral neuropathy of uremic patients on maintenance hemodialysis. And it is probably due to the fact that HP+HD effectively removes such plasma middle and macromolecular toxins as leptin, ET-1, PTH and β-2MG.

Topics: beta 2-Microglobulin; Endothelin-1; Hemoperfusion; Humans; Leptin; Parathyroid Hormone; Peripheral Nervous System Diseases; Renal Dialysis

To observe clinical therapeutic effect of mild-warm moxibustion on diabetic peripheral neuropathy (DPN) and to probe the mechanism.. Sixty cases of DPN were randomly divided into a mild-warm moxibustion group, an acupuncture group and a medication group, 20 cases in each group. In the mild-warm moxibustion group and the acupuncture group, the same points, Shenshu (BL 23), Pishu (BL 20), Zusanli (ST 36), Yongquan (KI 1), etc. were selected; and the medication group were treated with Mecobalamin tablets. Their therapeutic effects and changes of fasting blood-glucose (FBG), glycosylated hematoglobin (GHB), hemorheological indexes, plasma endothelin (ET), nitric oxide (NO) and malondialdehyde (MDA) before and after treatment were investigated.. The total effective rate was 90.0%, FBG, GHB, hemorheological indexes, plasma ET, NO and MDA significantly improved in the mild-warm moxibustion group (P < 0.01), with no significant difference as compared with those in the acupuncture group (P > 0.05), but with a significant difference as compared with the medication group (P < 0.05).. Mild-warm moxibustion has definite therapeutic effect on diabetic peripheral neuropathy, which is better than that of Mecobalamin.

Topics: Adult; Aged; Diabetic Neuropathies; Endothelin-1; Female; Hemodynamics; Humans; Male; Malondialdehyde; Middle Aged; Moxibustion; Nitric Oxide; Peripheral Nervous System Diseases

We evaluated the role of a mechanically-gated ion channel, Piezo2, in mechanical stimulation-induced enhancement of hyperalgesia produced by the pronociceptive vasoactive mediator endothelin-1, an innocuous mechanical stimulus-induced enhancement of hyperalgesia that is vascular endothelial cell dependent. We also evaluated its role in a preclinical model of a vascular endothelial cell dependent painful peripheral neuropathy.. The local administration of oligodeoxynucleotides antisense to Piezo2 mRNA, at the site of nociceptive testing in the rat's hind paw, but not intrathecally at the central terminal of the nociceptor, prevented innocuous stimulus-induced enhancement of hyperalgesia produced by endothelin-1 (100 ng). The mechanical hyperalgesia induced by oxaliplatin (2 mg/kg. i.v.), which was inhibited by impairing endothelial cell function, was similarly attenuated by local injection of the Piezo2 antisense. Polymerase chain reaction analysis demonstrated for the first time the presence of Piezo2 mRNA in endothelial cells.. These results support the hypothesis that Piezo2 is a mechano-transducer in the endothelial cell where it contributes to stimulus-dependent hyperalgesia, and a model of chemotherapy-induced painful peripheral neuropathy.

Topics: Animals; Antineoplastic Agents; Endothelial Cells; Endothelin-1; Gene Expression Profiling; Gene Expression Regulation; Hyperalgesia; Ion Channels; Male; Models, Animal; Oligonucleotides, Antisense; Organoplatinum Compounds; Oxaliplatin; Pain; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley; Touch

Endothelin-1 (ET-1) exists in endothelial cells as well as a variety of other cell types. The presence of ET-1 and its receptors in neurons suggests its possible role as a neurotransmitter and/or neuromodulator. Studies utilizing exogenous ET-1 have suggested that ET-1 affects pain transmission. This study was designed to examine the possible role(s) of neuronal ET-1 in pain processing. We produced neuron-specific ET-1 knockout mice using the Cre/loxP system with a synapsin I promoter and examined the effects produced by the lack of neuronal ET-1 on pain behavior using common pain models and a model of stress-induced analgesia. In acute nociceptive pain models, paw withdrawal thresholds to radiant heat and mechanical stimuli applied with von Frey hairs were significantly lower in the knockout mice compared with control. This indicated that the absence of neuronal ET-1 leads to greater sensitivity to acute nociceptive stimuli. After inflammation was produced by intraplantar injection of carrageenan, there was a significantly greater degree of thermal hyperalgesia and mechanical allodynia in the knockout mice even after the difference in baseline values was compensated. Furthermore, in a neuropathic pain model produced by spinal nerve ligation, there was also a greater degree of mechanical allodynia in the knockout mice. Finally, in a swim-stress model, the magnitude of stress-induced analgesia was less in the knockout mice, indicating the involvement of neuronal ET-1 in stress-induced analgesia. The results suggest that there is a basal release of ET-1 from neurons that affect baseline pain thresholds as well as an additional release during persistent pain states that acts to suppress the pain. The involvement of neuronal ET-1 in stress-induced analgesia further suggests its role in endogenous pain inhibitory systems. To confirm that ET-1 is released in persistent pain states and to determine which part of the CNS is involved, we measured the concentrations of ET-1 before and after inducing peripheral inflammation in different parts of the CNS involved in endogenous pain inhibitory systems in normal mice. We found that ET-1 was increased in the hypothalamus while no significant increase was observed in the midbrain, medulla and spinal cord. The results of the present study suggest that neuronal ET-1 is involved in endogenous pain inhibitory control likely via pathways through the hypothalamus.

Topics: Acute Disease; Animals; Disease Models, Animal; Endothelin-1; Hyperalgesia; Hypothalamus; Mice; Mice, Knockout; Neural Inhibition; Neural Pathways; Neurons; Pain; Pain Measurement; Pain Threshold; Pain, Intractable; Peripheral Nervous System Diseases; Physical Stimulation; Promoter Regions, Genetic; Reaction Time; Stress, Physiological; Synapsins