Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bradykinin is a nine amino acid peptide of the kinin family believed to play a role in pain mediation and in the regulation of blood pressure, fluid balance and smooth muscle contraction. Here we demonstrate that bradykinin is also a potent mitogen for a mutant Ha-ras-transfected cell line, Rat 13. The Rat 13 cells display two binding sites for bradykinin: a moderate number (52,000) of high affinity sites (Kd = 4.9 nM) co-exist with a much smaller number (1100) of very high-affinity sites (Kd = 2.7 pM). Ligand binding stimulates mitogenesis through the lower affinity receptors, which are classified as B2. These receptors are down-regulated in response to ligand. In contrast, Rat 1 cells (the cell line from which Rat 13 was derived) have only 4000 receptors per cell in total and respond weakly to bradykinin as a mitogen. Thus, expression of a mutant ras protein in Rat 13 cells increases their expression of the bradykinin receptor and their sensitivity to ligand stimulation of mitogenesis. Additional binding studies demonstrate that human A431 epithelial cells and Swiss mouse 3T3 fibroblasts also possess high-affinity sites for bradykinin.
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PMID:Bradykinin receptor number and sensitivity to ligand stimulation of mitogenesis is increased by expression of a mutant ras oncogene. 256 Nov 28

Bradykinin, alone or in combination with prostaglandin, is thought to produce pain in patients with coronary heart disease. To elucidate this further, we have investigated and compared serum bradykinin, TXB2 and 6 KPGF1 alpha levels in patients with silent myocardial ischemia (SMI, n = 18), painful myocardial ischemia (PMI, n = 8) and normal subjects (NL, n = 18). In addition, SMI and PMI subjects were given exercise testing and the results then compared. After Holter monitoring for 48 hours, exercise testing was performed. Blood was sampled in the morning between the Holter and exercise regimen. Maximal heart rate, systolic blood pressure and the double products were not significantly different between the SMI and PMI groups. The duration of exercise for the SMI group was 7.08 +/- 2.1 min vs 5.9 +/- 1.9 in the PMI group (p less than 0.10). Plasma bradykinin was 14 +/- 3 pg/ml in the SMI group and 15 +/- 3 in the PMI group (N.S), whereas it was 7 +/- 4 in the NL (p less than 0.05). The TXB2/6KPGF1 alpha for the SMI group was 1.3 +/- 0.3, which was significantly higher than that for the NL group (0.8 +/- 0.3, p less than 0.01), though this did not greatly differ from the PMI group (1.2 +/- 0.3). These results suggest that SMI patients under Holter monitoring who manifest no symptoms but show significant ST segment depressions must receive the same careful attention given to PMI patients. In both group of patients bradykinin and prostaglandin metabolism is similarly changed, as was demonstrated by exercise stress testing.
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PMID:Plasma bradykinin and prostaglandin metabolism and exercise testing in patients with silent myocardial ischemia compared with patients with painful myocardial ischemia. 262 77

Autoradiographic studies localize [3H]bradykinin receptor binding sites to the substantia gelatinosa, dorsal root, and a subset of small cells in both the dorsal root and trigeminal ganglia of the guinea pig. [3H]Bradykinin labeling is also observed over myocardial/coronary visceral afferent fibers. The localization of [3H]bradykinin receptors to nociceptive pathways supports a role for bradykinin in pain mediation. Several bradykinin antagonists block bradykinin-induced acute vascular pain in the rat. The bradykinin antagonists also relieve bradykinin- and urate-induced hyperalgesia in the rat paw. These results indicate that bradykinin is a physiologic mediator of pain and that bradykinin antagonists have analgesic activity in both acute and chronic pain models.
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PMID:Bradykinin as a pain mediator: receptors are localized to sensory neurons, and antagonists have analgesic actions. 289 57

Bradykinin (BK) is a nonpeptide, originally discovered in blood; recently BK has been localized in neurons and fibers of the hypothalamus. BK is a vasoactive substance which is involved in pain, inflammation and oedema. The present study demonstrates that BK is also a potent stimulator of prolactin (PRL) release from anterior pituitary cells in vitro. A significant enhancement of the release of PRL is observed at 1 nM BK. The stimulation of PRL release by BK is dose-dependent. This work shows that anterior pituitary cells in culture may serve as a useful model system in which to study the mechanism of action of BK.
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PMID:[Bradykinin stimulates prolactin release in vitro]. 295 Sep 75

Bradykinin is a potent pain-producing substance, yet little is known about its role in inflammation. The present study measured circulating levels of immunoreactive bradykinin in a clinical model of acute inflammation (oral surgery) and chronic inflammation (rheumatoid arthritis) and in the rat carrageenan model of inflammation. The effects of a kallikrein inhibitor (soybean trypsin inhibitor) on blocking bradykinin synthesis in vitro and its analgesic actions in the rat model were also evaluated. Levels of immunoreactive bradykinin increased threefold to fourfold during oral surgery. Levels were twofold to threefold greater in patients with rheumatoid arthritis compared with control subjects. Levels of immunoreactive bradykinin increased twofold in rats during carrageenan inflammation. Soybean trypsin inhibitor blocked synthesis of bradykinin in vitro and possessed analgesic activity in rats. The results indicate that the bradykinin system is activated during inflammation. Kallikrein inhibitors may represent a new class of analgesic/antiinflammatory drugs.
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PMID:Bradykinin is increased during acute and chronic inflammation: therapeutic implications. 319 62

The behaviour of normal birds and birds with ulcerated buccal lesions was described following oral stimulation with Acetylcholine chloride (ACh) and Bradykinin (BK). Both groups of birds showed normal oral behaviour but a number of birds with oral lesions showed a behaviour pattern which had been previously seen in our laboratory following nociceptive stimulation. The birds remained motionless in a crouch-like stance with the head pulled into the body and a significantly reduced number of alert head movements. The onset and duration of this immobility response was compared with reports of pain in humans in the blister-base test using similar concentrations of ACh and BK. It was concluded that nocifensive responses of the chicken fulfil many of the requirements for the definition of pain in animals.
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PMID:Oral lesions in the chicken: behavioural responses following nociceptive stimulation. 367 47

Effects of electrical stimulation of the periventricular gray (PVG) on spinothalamic tract (STT) cell activity were determined in 19 anesthetized monkeys (Macaca fascicularis). Twenty-two STT cells projected to the ventral posterior lateral nucleus (L-STT cells), 11 to the medial thalamus (M-STT cells), and 9 to both thalamic regions (LM-STT cells). All cells had somatic receptive fields and responded to electrical stimulation of cardiopulmonary sympathetic afferent fibers. PVG stimulation inhibited activity of 41 of 42 STT cells. Degree of inhibition of background activity was related to intensity and frequency. Stimulus currents of 300 microA or less completely silenced background activity of most cells. Thresholds for stimulus current averaged 100 +/- 20 microA and were unrelated to cell projection site, laminar location, or type of somatic or visceral input. However, lowest thresholds were found when the PVG electrodes were located within 0.5 mm of the third ventricle in the dorsomedial hypothalamus or nucleus reuniens of the thalamus. PVG stimulation inhibited responses of 22 of 22 cells to intracardiac injections of bradykinin. Bradykinin (2 micrograms/kg) increased cell activity from 15 +/- 3 to 31 +/- 5 spikes/s (P less than 0.01), and PVG stimulation (380 +/- 40 microA) reduced activity to 9 +/- 3 spikes/s (P less than 0.001). PVG stimulation inhibited responses of 33 of 33 STT cells to noxious pinch of skin or skin and muscle and responses of 8 of 8 cells to hair movement. Degree of inhibition of cell responses to noxious pinch was not significantly different from inhibition of responses to bradykinin. Effects of PVG stimulation on activity of six STT cells were studied before and after bilateral lesions were made in the dorsolateral funiculus (DLF). In no case did the lesions abolish or attenuate inhibitory effects of PVG stimulation. These results suggest that PVG may participate in descending inhibition of STT cells including cells mediating cardiac pain. The descending pathways are not located in the DLF. Further, descending inhibitory systems modulate STT cells projecting to both medial and lateral thalamus.
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PMID:Periventricular gray inhibition of thoracic spinothalamic cells projecting to medial and lateral thalamus. 371 68

A method for assessing inflammatory pain response was developed by modification of the formalin test. Formalin (0.5%, 25 microliters) was injected into the hindpaw of the mouse, and the durations spent in licking or biting response were measured as an indicator of pain response. The response curve was biphasic, having two peaks, from 0 to 5 min (first phase) and from 15 to 20 min (second phase). Morphine, ethylketocyclazocine, ketocyclazocine and pentazocine inhibited the response dose-dependently at the first and the second phases. Aspirin, oxyphenbutazone and dexamethasone inhibited only the second phase. Aminopyrine and mefenamic acid which acted at both central and peripheral sites inhibited both phases; however, the inhibition of the second phase was stronger than that of the first phase. Substance P (SP) antagonist inhibited only the first phase. Bradykinin (BK) inhibitor caused a inhibition of both first and second phases, and pretreatment of compound 48/80 and indomethacin inhibited only the second phase. From these facts, it was suggested that SP and BK played a role in the pain response at the first phase, and histamine, BK and PG were involved at the second phase. Naloxone produced hyperalgesia and bestatin produced analgesia at the second phase; then, it seems that the endogenous opioid system is activated by formalin stimulation and modulates the pain perception. Based on these findings, it is presumed that the pain of the first phase is evoked by the direct stimulation of the nerve fibers, and that of the second phase is due to the inflammatory reaction.
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PMID:[Studies of inflammatory pain response: related pain producing substance and endogenous opioid system]. 372 60

A mode of interaction of bradykinin with prostaglandins (PGs) in pain were compared with that in acute inflammation. When pain production was measured as an increase in reflex hypertensive response of the lightly anesthetized dogs after intrasplenic injection of bradykinin, the response was dependent to the doses (0.3-5 nmol) of bradykinin and that by the small doses (0.1-1 nmol) was blocked by intrasplenic infusion of indomethacin (0.54 mumol/min). The response to the threshold dose of bradykinin (0.3 nmol), which was suppressed during the indomethacin infusion, was potentiated by simultaneous injection of exogenous PGs. Order of the potency was PGI2 greater than PGH2 greater than PGE2 = TXA2 much greater than PGD2. Thus, it is clear that bradykinin induced pain through the generation of one of prostaglandins. On the other hand, the activity of bradykinin in plasma leakage was potentiated by simultaneous injection of PGE2, when tested in rabbit skin. In rat carrageenin-induced pleurisy, plasma prekallikrein was activated and high molecular weight (HMW) kininogen, not low molecular weight (LMW) kininogen, was consumed in the pleural cavity in the entire course of the pleurisy. Bradykinin played a role in plasma exudation in the pleurisy, because the plasma leakage was markedly inhibited in the rats, in which prekallikrein and HMW kininogen in plasma were depleted by intravenous bromelain. PGE2 was found in the pleural exudate, but the contribution of PGE2 itself to the plasma exudation seems to be only 10%. On the basis of the bradykinin release in the pleural cavity, once the PGE2 release was superimposed, the maximal plasma leakage was observed, indicating that PGE2 was released independently from bradykinin, and potentiated the plasma leakage by bradykinin.
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PMID:Different modes of interaction of bradykinin with prostaglandins in pain and acute inflammation. 381 4

Effects of injecting bradykinin (2 micrograms/kg) into the left atrium on spinothalamic tract neurons projecting to medial thalamus (M-STT cells), to the ventral posterior lateral nucleus of the thalamus (L-STT cells), or to both (LM-STT cells) were examined in 18 monkeys (Macaca fascicularis) anesthetized with alpha-chloralose. Bradykinin increased cell activity in 11/16 M-STT cells, 10/15 L-STT cells, and 4/7 LM-STT cells. One M-STT cell was inhibited. Peak responses to bradykinin of the three cell groups were not different. LM-STT cells began to respond and reached peak responses slightly earlier than the other two groups. Six M-STT, four L-STT, and two LM-STT cells became entrained to the cardiac cycle during their responses to bradykinin. Responses to bradykinin were not dependent on the type of somatic input or cell location. Responding cells most often received A delta- and C-fiber sympathetic input, but some responding cells had only A delta-input. These results demonstrate that in addition to L-STT cells STT cells projecting to the medial thalamus respond to a potentially noxious cardiac stimulus. These cells may participate in the motivational-affective component of cardiac pain.
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PMID:Effects of intracardiac bradykinin on T2-T5 medial spinothalamic cells. 402 72


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