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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extravascular activation of thrombocytes may contribute to nociceptor excitation and pain, since platelets store and, upon stimulation, release potential algogenic substances such as serotonin, histamine and precursor molecules of bradykinin. To test this hypothesis, a skin-nerve preparation of rat hairy skin, in vitro, was used that allows to record and characterize single afferent nerve fibers. In a first protocol, receptive fields of nociceptive C-fibers, at the corium side of the skin patch, were exposed to adenosine diphosphate (ADP), to heparinized human platelet-rich plasma (PRP) and to PRP activated by ADP. Such activated platelets excited 9/11 units characterized as mechano-heat responsive C-nociceptors (CMH); peak discharges of more than 10 spikes/s were observed. After application of activated PRP, 4/5 high threshold mechanosensitive C-units and 4/5 mechano-cold sensitive C-units became responsive to heat stimulation but only few of these fibers were excited (1/5 in each group). In a second series of experiments the exposure to native PRP was prolonged to test for the effect of spontaneous platelet activation resulting from cutaneous collagen. Prolonged exposure did, but not significantly, enhance fiber discharge. During subsequent exposure to activated PRP, the discharge commenced, on average, after a significant delay of about three minutes. With this protocol 5/7 CMH units were driven by activated platelets. Following both protocols, mechanical (v.Frey) and thermal thresholds of the CMH units were not significantly altered. The findings demonstrate that nociceptors can indeed be driven and sensitized by activated platelets. This pain inducing mechanism may be relevant to certain clinical conditions, and it appears promising to scrutinize the chemical factors involved.
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PMID:Activated human platelets in plasma excite nociceptors in rat skin, in vitro. 804 82

Twenty-two patients with intermittent claudication were included in a double-blinded, randomized trial comparing the effects of 25 treatments with intermittent suction and pressure (Vacusac treatment) to 25 placebo applications given over a period of two months. Twelve patients participated in an open trial investigating the effects of the same treatment on adenosine diphosphate (ADP)-induced platelet aggregation and fibrinolysis. Active treatment resulted in significant improvements in pain-free and maximal walking distances, whereas no changes could be found during placebo application. Active treatment caused significant increments in ADP-induced platelet aggregation, while the effects on fibrinolysis were uncertain. It is concluded that intermittent suction and pressure treatment offers a new approach for conservative treatment of intermittent claudication.
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PMID:[Positive effect of intermittent overpressure and underpressure (Vacusac) in intermittent claudication]. 801 40

The present study reports on the effects of a physical treatment modality in patients with intermittent claudication. During this treatment a major part of the skin surface is subjected to intermittent suction and pressure. In a previous, preliminary study the authors found a beneficial effect of this treatment in intermittent claudication. The study included 34 patients with moderate, stable intermittent claudication. Twenty-two patients participated in a double-blinded, randomized trial comparing the effects of 25 treatments to 25 placebo applications given over a period of two months. Twelve patients participated in an open trial investigating the possible effects of the treatment on platelet aggregation and fibrinolysis. Pain-free and maximal walking distances were measured on a treadmill, and systolic blood pressure was measured on the upper limb, the ankle, and the first toe bilaterally. The threshold for adenosine diphosphate (ADP)-induced platelet aggregation was tested, and the fibrinolytic activity was estimated from the euglobulin clot lysis time. Active treatment resulted in significant improvements in pain-free and maximal walking distances, whereas no changes could be found during placebo administration. The treatment caused significant increments in the ADP thresholds for platelet aggregation, while the effects on fibrinolysis were uncertain. It is concluded that intermittent suction and pressure treatment offers a new approach for conservative treatment of intermittent claudication.
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PMID:Beneficial effects of intermittent suction and pressure treatment in intermittent claudication. 842 80

A 74-year-old man was admitted because of swelling, pain and ecchymosis in the night lower extremity. A blood analysis revealed that Hb was 11.8g/dl, WBC 37,600/microliters, and platelet count 137.1 x 10(4)/microliters. The NAP value was high. Bone marrow examination disclosed marked megakaryocytic hyperplasia. Chromosomal analysis revealed 47, XY, +9. Hemostatic data were within normal ranges, but the 2nd aggregation of platelet by ADP was diminished. The serum beta-TG was 159, PF-4 56ng/ml, B12 1,100, UB12 BC 1,800pg/ml. Gastric fiberoscopy revealed gastric cancer and CT scan disclosed marked splenomegaly. Essential thrombocythemia (ET) coexisting with gastric cancer was diagnosed based on these examinations. He was treated with anti-platelet agents, busulfan and tegafur uracil, however thromboembolic symptoms suggesting central nervous system and peripheral vascular ischemia and gastrointestinal bleeding occurred. Among diagnostic criteria for ET established by the polycythemia vera study group, there is a category "No known cause for reactive thrombocytosis." The case reported here had gastric cancer which may have contributed to the elevated platelet count, however this case could be diagnosed as ET coexisting with gastric cancer because of the above various clinical signs and laboratory results. Although then are few reports of the coexistence of other malignancies in ET, there may be many more similar cases because of the age preponderance in ET. In order to diagnose ET more precisely, more strict diagnostic criteria are needed.
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PMID:[Coexistence of essential thrombocythemia and gastric cancer]. 849 22

The general pharmacology of the new antimuscarinic compound vamicamide (FK176, (+/-)-(2R*, 4R*)-4-dimethylamino-2-phenyl-2- (2-pyridyl)valeramide, CAS 132373-81-0) was investigated using mice, rats, guinea pigs and dogs, and was in part compared with that of oxybutynin hydrochloride (oxybutynin, CAS 1508-65-2), a similar type of compound. 1. Vamicamide induced mydriasis after oral administration (p.o.) of 10 mg/kg or more, and suppressed defecation after 32 mg/kg or more in the general activity and behavior test with rats. 2. Vamicamide increased spontaneous locomotor activity in mice at 32 mg/kg or more (p.o.) and suppressed tonic convulsions in the electroconvulsive shock test with mice at 100 mg/kg. The compound at 10-100 mg/kg (p.o) did not show significant effects on hexobarbital-induced anesthesia, pentetrazole-induced convulsions and pain response by Haffner's method in mice, body temperature in rats or spontaneous electroencephalogram (EEG) in rabbits. On the other hand, oxybutynin increased high voltage slow waves of spontaneous EEG in rabbits at 32 mg/kg or more (p.o.) and prolonged hexobarbital-induced anesthesia time in mice at 100 mg/kg. 3. Vamicamide in concentrations of 0.001-1% (1 x 10(-4)-1 x 10(-1) g/ml) did not show local anesthetic effect on the corneal reflex test with guinea pigs. The compound in concentrations of 1 x 10(-5) and 1 x 10(-4) g/ml also had no effects on contractions of the isolated rat diaphragm caused by electrical stimulation of the phrenic nerve. 4. Vamicamide on the highest concentration of 1 x 10(-4) g/ml augmented contractions of isolated rat vas deferens induced by noradrenaline, resting tonus of the isolated guinea pig trachea, and contractile force of spontaneous movement of the isolated rat nonpregnant uterus. The compound at 1 x 10(-4) g/ml had no significant effects on KCl-induced contraction of the isolated rat thoracic aorta. 5. Vamicamide elevated systemic blood pressure and increased heart rate but had no effects on respiratory movement of the chest in conscious dogs at an oral dose of 10 mg/kg or more. The compound in intraduodenal (i.d.) doses of 3.2-32 mg/kg had no effect on femoral blood flow in anesthetized dogs. Vamicamide augmented contractile force and reduced beating rate in isolated guinea pig atria at a concentration of 1 x 10(-5) g/ml or more. Oxybutynin increased heart rate at 3.2 mg/kg or more (p.o.), and elevated blood pressure at 10 mg/kg or more in conscious dogs. 6. Vamicamide slightly inhibited small intestinal transit in rats at 3.2 mg/kg or more (p.o.). On the other hand, oxybutynin inhibited the transit in rats at 0.32 mg/kg or more. 7. Vamicamide had no effects on urine volume, urinary excretion of Na+, K+, Cl- and uric acid in rats at an oral dose of 100 mg/kg or less, or on renal function in anesthetized dogs at an i.d. dose of 32 mg/kg or less. 8. Vamicamide showed no effects on bleeding time in mice at 100 mg/kg p.o., rabbit platelet aggregation induced by adenosine diphosphate or collagen at 1 x 10(-4) g/ml, blood coagulation systems in rats at 100 mg/kg p.o., or hemolysis on rabbit blood at a concentration of 1% or less. Thus, vamicamide in the doses used inhibited gastrointestinal motility, and caused mydriasis as effects possibly due to its anticholinergic action. The compound had no effects on the central nervous system, cardiovascular system, renal functions, or blood system.
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PMID:General pharmacology of the new antimuscarinic compound vamicamide. 859 84

General pharmacological effects of recombinant human basic fibroblast growth factor (bFGF) were investigated. 1. Central nervous system: Basic FGF produced almost no effect on the general symptoms and behaviors of mice. Basic FGF did not influence the spontaneous motor activity, hexobarbital-induced anesthesia, electroshock seizure threshold, pentylenetetrazole-induced seizure in mice and normal body temperature and spinal reflex in rats up to a dose of 1 mg/kg (s.c., i.v.). As regards pain sensation, it inhibited the acetic acid-induced writhing at 1 mg/kg (s.c.). No abnormal waves were observed in spontaneous EEG of the rabbit up to 1 mg/kg (i.v.) of bFGF, but at 0.1 mg/kg it had a slight effect on the ratio of EEG levels and at 1 mg/kg induced an increase in rest period, disappearance in the period of fast wave sleep and a decrease in the period of deep sleep. 2. Somatic nervous system: Basic FGF did not influence the corneal reflex, twitch response of the skin and diaphragm-phrenic nerve preparations. 3. Autonomic nervous system and smooth muscle: Basic FGF showed little effects on the spontaneous movement of the isolated ileum, contraction induced by various agonists in isolated ileum, resting tension and noradrenaline(NA)-induced contraction of the aorta, resting tension and histamine-induced contraction of isolated trachea, spontaneous movement and 5-HT-induced contraction of isolated strips of stomach fundus, NA-induced contraction of isolated vas deferens of the rat up to the concentration of 10(-4) g/ml. Basic FGF augmented the tone of the isolated non-pregnant uterus at the concentrations of 10(-5) g/ml and above and inhibited or tended to inhibit the contractile tension of non-pregnant or pregnant uterus at 10(-4) g/ml, but it did not influence the spontaneous movement of the uterus, either the non-pregnant or pregnant, under in situ conditions even at a dose of 1 mg/kg (i.v.). Basic FGF did not influence the pupil size. 4. Respiratory and circulatory systems: Basic FGF had no effect on the isolated heart. The influence was not exerted on the heart rate for the isolated atria but slight inhibition of contractile force was observed at 10(-4) g/ml. In anesthetized dogs a decrease in blood pressure, a slight increase in heart rate and respiratory rate and a decrease in femoral blood flow were observed at 0.01 and 0.1 mg/kg (i.v.) of bFGF Similarly, a slight increase in heart rate and a slight decrease of blood pressure were observed at 1 mg/kg (s.c.) in conscious rats. 5. Digestive system: Administration of bFGF at 1 mg/kg did not result in changes in the transport capacity within the gastrointestinal tract (s.c., i.v.) and the secretion of the gastric juice (s.c.). 6. Urine output and electrolyte metabolism: Basic FGF produced a decrease in urinary Na+ excretion at 1 mg/kg (s.c.), and showed a tendency to increase in urinary volume at 0.01 and 0.1 mg/kg (i.v.). At 1 mg/kg (i.v.) urinary excretion of Na+ and Cl- was decreased significantly. It had no effect on the ability of rats to excrete PSP (phenol red) up to 1 mg/kg (s.c.). 7. Blood system: Basic FGF did not influence the coagulation time of the whole blood, prothrombin time and activated partial thromboplastin time of rats up to 1 mg/kg (s.c., i.v.). It did not influence the aggregation of rabbit platelets induced by collagen and ADP up to 10(-4) g/ml. Basic FGF at concentration of 10(-4) g/ml exhibited no hemolytic action. 8. Local action: Plantar subcutaneous injection of bFGF at above 0.005 mg/site induced edema by itself on and after the next day, and also reinforced carrageenin-induced edema from 1 day after injection. The results show that bFGF did not produce any acute effects on the somatic nervous system, autonomic nervous system, smooth muscle and blood system. In contrast, bFGF produced slight effects on the circulatory system, central nervous system and kidney function when injected systemically. Subcutaneous administration may produce edema at the s
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PMID:General pharmacology of recombinant human basic fibroblast growth factor. 884 46

The impairment of endothelial function in hypercholesterolaemic animals and humans is known to be reversed by intravenous infusions of L-arginine (L-ARG), the precursor of NO. 22 patients with peripheral arterial obstructive disease (PAOD) received L-ARG (60 mmol) as intravenous infusions, each lasting three hours, daily for seven consecutive days. This treatment resulted in elongation of the painfree and maximum walking distances, as well as shortening of the period of time required for pain relief after walking the maximum distance. A rise in the ankle/arm pressure ratio (AAPR) was associated with an increase of arterial blood flow in both calves. The transcutaneous oxygen tension (tcpO2) in the ischaemic foot was also increased. After the 1st and the 7th infusion of L-ARG the spontaneous (PAR) as well as the ADP- and collagen-induced platelet aggregation were suppressed, the euglobulin clot lysis time (ECLT) shortened, plasma levels of platelet activator inhibitor (PAI) decreased, and cGMP levels increased. These data indicate beneficial effects of L-ARG as a therapeutic agent in patients with PAOD. We presume that in these patients high doses of exogenous L-ARG can be partially converted to NO.
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PMID:Treatment with L-arginine is likely to stimulate generation of nitric oxide in patients with peripheral arterial obstructive disease. 886 84

Pertussis toxin (PTX), which causes the ADP-ribosylation and thereby inactivation of Gi-proteins, has been employed in analgesia testing to elucidate receptors that are coupled to inhibitory G-proteins, such as the mu-opioid receptor. Consistent with previous findings, the antinociceptive effects of morphine (1-10 microg) as measured by tail-flick latency using a 55 degrees C water bath, were blocked by a single intrathecal injection of 0.5 microg PTX 6 days prior to intrathecal morphine administration. In addition, mice treated intrathecally with 0.5 microg of PTX had significantly shorter baseline tail-flick latencies compared with vehicle treated mice using a 55 degrees C water bath when tested 6 days after PTX or vehicle administration. Morphine-induced antinociception was blocked in a dose-dependent manner by PTX with complete blockade of morphine following a 0.3-microg dose of PTX. Further, mice administered 0.1 microg or 0.3 microg PTX intrathecally had significantly shorter tail-flick latencies compared with vehicle injected mice using a 40, 45 or 50 degrees C water bath when tested 7 days after intrathecal injection. Shorter tail-flick latencies were observed at 45 degrees C as early as 48 h after intrathecal administration of 0.03, 0.1 or 0.3 microg PTX and these shorter tail-flick latencies were observed up to 90 days after intrathecal PTX administration. The intrathecal administration of PTX caused hyperalgesia and allodynia that appears similar to the symptoms reported by patients suffering from neuropathic pain, and suggests that deficiencies in inhibitory systems, as compared with increases in excitatory systems, may play a role in the pathophysiology of at least some central or neuropathic pain states.
Pain 1997 Apr
PMID:Intrathecal pertussis toxin produces hyperalgesia and allodynia in mice. 915 Feb 97

Misoprostol, the oral analogue of alprostadil was used for the treatment of 20 patients (aged 40-60) with peripheral arterial disease according to Fontaine's classification at stages IIa and IIb (PAD). All patients received 200 micrograms of misoprostol 3 times a day during a month. The therapy with misoprostol resulted in a clinical improvement in all patients. Elongation of pain free (before treatment 129 m +/- 78 m, after treatment 214 m +/- 109 m) and maximum walking distance (before treatment 304 m +/- 169 m, after treatment 471 m +/- 264 m) was observed. At the same time a shortening of the pain duration was noted (before treatment 100 sec +/- 37 sec, after treatment 71 sec +/- 23 sec). The ankle/arm pressure ratio (AAPR) and arterial blood flow increased in both limbs after 4 weeks of the treatment. Activation of the fibrinolytic system was seen in the course of the therapy (shortening of euglobulin clot lysis time-ECLT and increase in t-PA activity). The platelets became less sensitive to ADP and collagen after intake of misoprostol. The results justify administration of misoprostol as a new therapeutic agent for the treatment of patients with PAD.
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PMID:[Misoprostol--oral prostanoid--the first clinical trial for use in patients with peripheral vascular disease]. 948 Apr 58

The G protein Go is highly expressed in neurons and mediates effects of a group of rhodopsin-like receptors that includes the opioid, alpha2-adrenergic, M2 muscarinic, and somatostatin receptors. In vitro, Go is also activated by growth cone-associated protein of Mr 43,000 (GAP43) and the Alzheimer amyloid precursor protein, but it is not known whether this occurs in intact cells. To learn about the roles that Go may play in intact cells and whole body homeostasis, we disrupted the gene encoding the alpha subunits of Go in embryonic stem cells and derived Go-deficient mice. Mice with a disrupted alphao gene (alphao-/- mice) lived but had an average half-life of only about 7 weeks. No Goalpha was detectable in homogenates of alphao-/- mice by ADP-ribosylation with pertussis toxin. At the cellular level, inhibition of cardiac adenylyl cyclase by carbachol (50-55% at saturation) was unaffected, but inhibition of Ca2+ channel currents by opioid receptor agonist in dorsal root ganglion cells was decreased by 30%, and in 25% of the alphao-/- cells examined, the Ca2+ channel was activated at voltages that were 13.3 +/- 1.7 mV lower than in their counterparts. Loss of alphao was not accompanied by appearance of significant amounts of active free betagamma dimers (prepulse test). At the level of the living animal, Go-deficient mice are hyperalgesic (hot-plate test) and display a severe motor control impairment (falling from rotarods and 1-inch wide beams). In spite of this deficiency, alphao-/- mice are hyperactive and exhibit a turning behavior that has them running in circles for hours on end, both in cages and in open-field tests. Except for one, all alphao-/- mice turned only counterclockwise. These findings indicate that Go plays a major role in motor control, in motor behavior, and in pain perception and also predict involvement of Go in Ca2+ channel regulation by an unknown mechanism.
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PMID:Multiple neurological abnormalities in mice deficient in the G protein Go. 950 Dec 52


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