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

Synthetic bradykinin, a nonapeptide formed from alpha-2 globulin in plasma, injected intra-arterially or intraperitoneally in cats in doses of 10-50 mug, evoked activity in the central nervous system in pathways associated with the signaling of pain. Similar injections of bradykinin in intact normal cats and dogs evoked manifestations of pain, and in conscious humans elicited verbal reports of pain perceived in the area of injection. Single unit activity was recorded in the medial reticular formation of the brainstem, in the medial thalamus and, more laterally, among the posterior group nuclei and the suprageniculate nucleus. Bradykinin did not evoke any cortical or subcortical slow potentials such as those evoked by electrical stimulation of the foot pads. When bradykinin was given together with the electrical stimulus, the responses evoked by the latter were blocked. Morphines uppressed bradykinin-evoked activity. Aspirin caused marked fluctuations in activity, unrelated to the bradykinin injection; the bradykinin block of evoked potentials could no longer be observed after aspirin dosage. The results are discussed in terms of the peripheral and central sites of analgesic action and the likelihood of the existence of chemosensitive pain receptors.
 ...
PMID:Central nervous system activity associated with the pain evoked by bradykinin and its alteration by morphine and aspirin. 525 60

Polypeptides are endogenous agents, involved in the regulation of many physiologic functions and the pathogenesis of several diseases. Polypeptide antagonists form a group of new chemical entities which may provide valid therapeutic agents. Some polypeptides (angiotensin, kinins) are released through the action of proteolytic enzymes (renin, kallikreins) and act as hormones or autacoids; others (substance P, neurotensin) are synthetized by nervous cells to serve as neurotransmitters or neuromodulators. The main homeostatic role of the renin-angiotensin system is to uphold high systemic arterial blood pressure. Overproduction of renin and insufficient checking of renin secretion are among the most common causes of arterial hypertension. Several forms of arterial hypertension (neurovascular, idiopathic) benefit from a reduction in renin-angiotensin system activity. This is achieved either through decreasing renin secretion, by inhibiting conversion of angiotensin I into angiotensin II, or through blocking the peripheral actions (at the receptor sites) of angiotensin II. Renin secretion is very significantly reduced by beta-blocking agents (propranolol); conversion of angiotensin I into angiotensin II is inhibited by teprotide, captopril and their derivatives; peripheral actions of angiotensin II are blocked by saralasin. Bradykinin and related agents produce vasodilation, increase vascular permeability and stimulate pain fibers. Kinins thus reproduce the cardinal features of inflammation and are held to be mediators of the inflammatory reaction. The substance P neuropeptide is found in the brain and bowel; it may act as a transmitter of the sensation of pain at the spinal cord and central nervous system sites. Among other effects outside of the brain, substance P is a potent vasodilator and inhibits renin secretion. Neurotensin is a neuropeptide which produces hypothermia, muscular relaxation and analgesia. Outside of the brain, this peptide is involved in the regulation of gastric secretion, intestinal motility and insulin and glucagon secretion. The vasoactive intestinal peptide, found in certain cholinergic nerve endings, is a large peptide which inhibits gastric secretion, intestinal motility and vascular tone.
 ...
PMID:[Polypeptides and antagonists]. 620 6

Acute inflammatory paw edema of rats was formed by the injection of 0.5% Mycobacterium tuberculosis-liquid parraffin suspension into the hind paw, and then the pain threshold of the inflamed paw decreased. At that time, the rats showed a three-legged gait, namely, the lame walking reaction. The reaction was inhibited by acidic nonsteroidal anti-inflammatory drugs, e.g., indomethacin, ibuprofen and aspirin, inhibitors of prostaglandins biosynthesis, at a lower dose level than those in the Randall-Selitto test using yeast edematous rats and in the flection tests using adjuvant arthritic or silver nitrate arthritic rats. On the other hand, basic nonsteroidal anti-inflammatory drugs, e.g., tiaramide HC1, mepirizole and perisoxal citrate, not inhibitors of prostaglandins biosynthesis, were less potent than the acidic nonsteroidal anti-inflammatory drugs in the inhibition of the lame walking reaction. When prostaglandin E2 was injected into the inflamed paw, the inhibitory effects of acidic non-steroidal anti-inflammatory drugs on the reaction disappeared, but those of the basic nonsteroidal anti-inflammatory drugs didn't disappear. Bradykinin had no influence on the effects of both acidic and basic nonsteroidal anti-inflammatory drugs in the inhibition of the reaction. Analgesic evaluation with the lame walking reaction is more sensitive than with the Randall-Selitto or the flection methods. Morphine, pentazocine and acetaminophen inhibited the reaction, and these effects didn't disappear by the injection of prostaglandin E2 into the inflamed paw. These results suggest that prostaglandins play important roles in inflammatory pain, and the lameness test can serve as a new method for evaluating analgesics such as anti-inflammatory drugs and for investigating the mechanism of inflammatory pain.
 ...
PMID:[Effects of anti-inflammatory drugs on the lame walking reaction in adjuvant-induced edematous rats]. 648 69

Bradykinin stimulates afferent fibers arising in the heart and may be involved in the mediation of anginal pain and the pain associated with myocardial infarction. The sensation of pain requires that noxious information reach the brain. The purpose of the present study was to determine whether the spinothalamic tract is involved in transmitting noxious information from the heart to the brain. Bradykinin was injected (0.3-3.5 micrograms/kg) into the heart via a catheter in the left atrium while we recorded from single spinothalamic cells in the C8 to T5 spinal segments. Thirty-one of 41 cells responded to bradykinin. The responses of 12 cells were characterized by both an increase in discharge rate and entrainment of cell activity with the cardiac cycle. Eighteen cells responded with only an increased rate, and one cell exhibited only entrainment of cell activity with the cardiac cycle. The mean onset of increased cell activity occurred 15 seconds following drug injection, and the average duration of the response was 54 seconds. Thirty cells increased their mean discharge rate from 11 +/- 2.5 to 29 +/- 4.4 spikes/second. Thus, some spinothalamic cells probably received input from both mechanosensitive and chemosensitive afferents. Tachyphylaxis to repeated doses of bradykinin was observed in 41% of cells. Cells responding to bradykinin had a spontaneous discharge rate that was significantly greater than that of nonresponding cells. Cells did not require input from C-fiber afferents to respond to bradykinin. No statistically significant relationships were found among anatomical locations (laminae and segments) and responses to bradykinin, although cells in lamina I seemed to be less responsive than more ventrally located cells. We conclude that the spinothalamic tract may be involved in the sensation of cardiac pain.
 ...
PMID:Responses of thoracic spinothalamic neurons to intracardiac injection of bradykinin in the monkey. 708 91

The effect of bradykinin on microcirculation was studied in vivo on the rat mesentery. Bradykinin (0.01--10 micrograms) caused three types of reactions of arterioles and venules (constriction, dilatation, no changes in the diameter) in relation to the dose used. Preliminary application of noradrenaline changed the sensitivity of microvessels to bradykinin towards the increased frequency of dilatation. The increased permeability by red cells in postcapillaries and in venules arose in the areas of the greatest stretch (sites of confluences and ridges of vessels wavy in outline) and was accompanied by deformation and shortening of venules. It was disclosed that bradykinin exerted a pronounced pain effect that promoted awakening of the animals from anesthesia.
 ...
PMID:[Relationship between the effect of bradykinin on microvessels and their initial tonus]. 721 1

Cats were used to assess the significance of differences in animal preparations in the study of anesthetic-induced analgesia. Comparison was made between pentobarbital-anesthetized and decerebrate non-anesthetized cats. Bradykinin dissolved in normal saline was injected into the femoral artery as a noxious stimulus, and the neural response in the spinal cord lateral funiculus was recorded using the multi-unit activity technique. The magnitude of the neural response and the changes in spontaneous firing were compared before and after cervical cord transection at C1. Before the transection, the response was greater in anesthetized than in decerebrate cats. The cord transection potentiated the response in both preparations, but the degree of potentiation was greater in decerebrate than in anesthetized cats. These studies confirmed the presence of a descending pain inhibition system acting tonically on the nociceptive neural mechanisms in the spinal cord, and indicated the susceptibility of this system to pentobarbital. We conclude that pretreatment with pentobarbital induces pharmacologically a state of partial spinal cord transection and reduces the effects of drugs acting through supraspinal CNS structures.
 ...
PMID:Pentobarbital-anesthetized and decerebrate cats reveal different neurological responses in anesthetic-induced analgesia. 731 83

1. We have examined the effect of bradykinin on impulse traffic in sympathetic afferent fibres from the heart, great vessels and pleura, and have attempted to identify cardiac nociceptors that on the basis of their functional characteristics might have a role in the initiation of cardiac pain. 2. In anaesthetized cats, we recorded afferent impulses from 'single-fibre' slips of the left 2nd--5th thoracic rami communicantes and associated chain, and selected fibres arising from endings in the heart, great vessels, pericardium and pleura. We applied bradykinin solution (0 . 1--1 . 0 microgram/ml.) locally to the site of the ending; we also injected bradykinin (0 . 3--1 . 0 microgram/kg) into the left atrium. 3. Afferent endings excited by bradykinin (159 of 191 tested) were of two types. The larger group (140) were primarily mechanoreceptors with A delta of C fibres (mean conduction velocity, 7 . 5 +/- 0 . 6 m/sec). They were very sensitive to light touch. Those located in the heart, great vessels or overlying pleura had a cardiac rhythm of discharge and were stimulated by an increase in blood pressure or cardiac volume. 4. Bradykinin increased mechanoreceptor firing from 0 . 7 +/- to 5 . 0 +/- 0 . 3 (mean +/- S.E. of mean) impulses/sec. Some endings appeared to be stimulated directly by bradykinin, others sensitized by it so that they responded more vigorously to the pulsatile mechanical stimulation associated with the cardiac cycle. 5. The smaller group of eighteen endings, of which ten were in the left ventricle, were primarily chemosensitive. Most had C fibres, a few had A delta fibres (mean conduction velocity, 2 . 3 +/- 0 . 7 m/sec). They were insensitive to light touch. With one exception they never fired with a cardiac rhythm, and even large increases in aortic or left ventricular pressure had little effect on impulse frequency. 6. Chemosensitive endings were stimulated by bradykinin, impulse activity increasing from 0 . 6 to 15 . 6 +/- 1 . 3 impulses/sec and remaining above the control level for 1-3 min. The evoked discharge, which was either continuous or occurred in irregular bursts, was not secondary to mechanical changes in the heart and great vessels. 7. Tachyphylaxis occurred when the interval between successive applications of bradykinin was 20 min or less. It was a feature of the response of both mechanosensitive and chemosensitive endings. 8. Because of their responsiveness to changes in pressure and their sensitivity to light touch, the mechanosensitive endings appear to be unlikely to subserve a primarily nociceptive function, although they may be responsible for evoking some of the components of the pseudoaffective response. By contrast, the chemosensitive endings appear well fitted to act as cardiac nociceptors.
 ...
PMID:Search for a cardiac nociceptor: stimulation by bradykinin of sympathetic afferent nerve endings in the heart of the cat. 746 75

This work investigated the role of bradykinin in viscerosensitivity before and during inflammation in two models of visceral pain induced by rectal distension (RD) or "abdominal distension" (AD) in rats. RD induced both inhibition of colonic motility and an increase of abdominal spike bursts. Bradykinin receptor antagonist, Hoe 140 did not affect any of the RD-induced responses. After TNB-induced rectal inflammation, colonic inhibition and the number of abdominal contractions were enhanced. Hoe 140 selectively reduced the abdominal response to the highest distension volume, without affecting the colonic response. In AD group, acetic acid inhibited gastric emptying and increased the number of abdominal contractions, whereas the same volume of saline did not affect any of the responses. Before inflammation, Hoe 140 (1-5 mg/kg, intraperitoneally) did not affect per se abdominal and gastric emptying responses; in contrast, at 5 mg/kg, intraperitoneally, it reduced significantly (P < 0.05) both acetic acid-induced responses. We conclude that bradykinin is involved in viscerosensitivity changes related to abdominal and rectal distension in inflammatory conditions.
 ...
PMID:Influence of bradykinin in gastrointestinal disorders and visceral pain induced by acute or chronic inflammation in rats. 755 43

1. We made recordings from rat dorsal root filaments to study unmyelinated afferent units (conduction velocity < or = 1.5 m/s) associated with deep paraspinal tissues of the dorsal sacrum and proximal tail. Data from 57 unmyelinated units were analyzed in 47 experiments. Receptive fields were identified in intact animals and then surgically isolated using microdissection. Units were characterized using mechanical, noxious chemical, and thermal stimuli. 2. These recordings revealed innervation of the nerve sheaths and surrounding connective tissue, muscles, tendons, and tissue apposed to the undersurface of the skin. No units were found with receptive fields directly on joint capsular tissue. The receptive fields of the units were often multiple and located in more than one tissue; 31 of 57 units showed convergence from different tissues. 3. The units with receptive fields on neurovascular bundles shared sensitivities with other deep tissue units described in this and other reports. These units may have clinical importance in pain due to peripheral neuropathies. 4. The units initially responded to strong mechanical stimulation of the intact animal and often to noxious stretch of the tail. Once surgically isolated, an individual unit's threshold to mechanical stimuli appeared lower. 5. Capsaicin (0.001%-0.1%) elicited responses in 81% (17 of 21) of the units tested. Bradykinin (20 micrograms/ml) elicited responses in 45% (10 of 22) of the units tested. Noxious cold (4-10 degrees C) and hot (55 degrees C) stimulation elicited discharges from 33% (5 of 15) and 25% (5 of 20) of the units tested, respectively. 6. The unmyelinated units had similar mechanical, chemical, and thermal sensitivities. These similarities and the observed convergence only allowed separation of units by the tissue in which the ending was found, and did not allow further classification. 7. The prevalence of background discharge suggested that many units were sensitized during the experiments. 8. The sensitivities of these paraspinal units were similar to those reported for other tissues. Because of the anatomic similarity of the paraspinal tissues of the proximal tail and the lumbar spine, the conclusions of the present study can be related to the lumbar spine. These afferent units are thought to participate in nociception from the deep paraspinal tissues.
 ...
PMID:Unmyelinated nociceptors of rat paraspinal tissues. 762 77

Bradykinin (BK), an important inflammatory mediator and potent algogenic substance, is supposed to contribute to the generation of arthritic hyperalgesia and pain. The present study was undertaken to examine if an experimental kaolin/carrageenan arthritis sensitizes articular afferents to BK in the cat's knee joint using two different approaches. First, the proportion of afferent units activated by BK was assessed in fully inflamed joints and compared with corresponding data of normal knee joints. BK (injected i.a. as a bolus close to the joint) at the dose of 2.6 micrograms activated 60% of the units of groups II-IV in the inflamed state, compared to 71% in normal joints. The proportions of low- and high-threshold afferents activated by BK were similar, but more spontaneously active units than units without ongoing activity responded to BK both in inflamed and normal knee joints. Second, the responsiveness of individual afferent units to BK was examined during the development of inflammation. Units not activated by BK remained unresponsive after inflammation. From 11 units activated by BK, 3 units lost their responsiveness and in 4 other units the response to BK was reduced within 2-6 h after the onset of inflammation. Only in 4 units was the BK response increased in the inflamed joint. It is concluded that desensitizing rather than sensitizing processes are involved to change the response behavior of articular afferents to BK during acute experimental inflammation.
Pain 1994 Dec
PMID:Responsiveness of slowly conducting articular afferents to bradykinin: effects of an experimental arthritis. 770 7


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>