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)

1. Bradykinin (0.02-5 microgram) applied to the epicardium of the left ventricle in the open-chest, anaesthetized dog, elicits dose-related reflex pressor effects and acceleration of the heart rate. 2. Bradykinin-induced reflex tachycardia was suppressed after the blockade of beta-adrenoceptors with propranolol, whereas reflex pressor responses were prevented by blocking the alpha-adrenoceptor sites with phenoxybenzamine. 3. Vagotomy and atropine treatment did not affect reflex hypertension and tachycardia to epicardial bradykinin. 4. After spinal section at C1, the pressor responses to epicardial bradykinin were significantly reduced, but still present in all but one experiment. A small acceleration of the heart occurred in two out of five spinal dogs with intact vagi and was absent in three vagotomized spinal dogs. 5. The results indicate the reflex activation of the sympathetic outflow to the heart and blood vessels, mediated mainly at a supraspinal level as a predominant mechanism for the cardiovascular response initiated by bradykinin-induced stimulation of cardiac pain receptors.
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PMID:Sympathetic cardiovascular reflex initiated by bradykinin-induced stimulation of cardiac pain receptors in the dog. 26 62

A method for determining the vocalization response to algesic agents in conscious guinea pigs is described. Retrograde injection of small amounts of algesic agents into the femoral artery caused transient but obvious vocalization response in a dose-dependent manner. The vocal sound was converted into electrical signals and the envelope of the sound obtained by a peak detector circuit was recorded on an ink-writing oscillograph. The area of the vocalization response circumscribed by a base line and the envelope tracing of the vocal sound was also recorded. Bradykinin, kallidin, acetylcholine (ACh) and nicotine caused the vocalization response, while substance P, histamine, bethanechol, methacholine, serotonin, kallikrein and prostaglandins E1 and E2 caused no or little response. No detectable tachyphylaxis to bradykinin, ACh and nicotine was observed. The pretreatment with hexamethonium abolished the response induced by ACh or nicotine but not the response induced by bradykinin. These results suggest that the paravascular pain receptor of the femoral artery excited by ACh is nicotinic in character. Subcutaneous injection of morphine, pentazocine, diclofenac and aminopyrine inhibited the vocalization response induced by bradykinin in a dose-dependent manner.
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PMID:Vocalization response to close-arterial injection of bradykinin and other algesic agents in guinea pigs and its application to quantitative assessment of analgesic agents. 43 Mar 71

1 The isolated perfused ear of the rabbit connected to the body only by its nerve, was used to investigate the influence of prostaglandin F2alpha on the algesic effect of bradykinin and acetylcholine. 2 Bradykinin and acetylcholine, following intra-arterial injection into the isolated perfused ear elicited a dose-related reflex fall in blood pressure due to stimulation of paravascular pain receptors (= algesic effect). 3 Infusion of prostaglandin F2alpha (0.1 to 1 ng/ml) into the rabbit ear reduced the algesic effect of bradykinin but not that of acetylcholine. 4 The onset of the reflex fall in blood pressure by bradykinin but not that by acetylcholine was delayed by infusion of prostaglandin F2alpha into the ear. 5 Infusion of prostaglandin E1 into the rabbit ear led to an enhancement of the algesic effect of bradykinin and acetylcholine. Enhancement of both effects was abolished by infusion of prostaglandin F2alpha. 6 During inhibition of the endogenous synthesis of prostaglandins (mainly E-type) by indomethacin, a low concentration of prostaglandin F2alpha no longer reduced the algesic effect of bradykinin. However, a high concentration of F2alpha continued to enhance the effect of bradykinin and acetylcholine. 7 Prostaglandin F2alpha influenced neither the brief reduction in venous outflow produced by bradykinin nor the brief increase in venous outflow caused by acetylcholine. 8 The results suggest that prostaglandin F2alpha does not directly reduce the effect of bradykinin but inhibits the enhancement of its algesic effect produced by prostaglandin E that is released endogenously by bradykinin. That the algesic effect of acetylcholine is not reduced by prostaglandin F2alpha is in keeping with its releasing very little endogenous prostaglandin E.
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PMID:Prostaglandin F2alpha reduces the algesic effect of bradykinin by antagonizing the pain enhancing action of endogenously released prostaglandin E. 84 80

Application of bradykinin to the exposed ventricular surface of the dog heart elicits a reflex cardiovascular response which includes a rise in blood pressure, tachycardia, renal vasoconstriction and muscular vasodilation. The reflex response depends on the dose of bradykinin and is increased by concomitant application of prostaglandin E1 or E2 and reduced by indomethacin. Temporary occlusion of the coronary artery supplying the area of the ventricle under study also sensitized the heart to topical application of bradykinin. Bradykinin and prostaglandins are released by the heart during ischaemia. We suggest, therefore, that bradykinin and prostaglandins acting in concert are the natural stimulus for excitation of the sensory receptors signalling the pain of myocardial ischaemia. We also suggest that the nervous reflex which arises from activation of sympathetic sensory nerve endings is the mechanism subserving the cardiovascular events which accompany anginal attacks.
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PMID:An excitatory nociceptive cardiac reflex elicited by bradykinin and potentiated by prostaglandins and myocardial ischaemia. 95 16

Kinins, the biologically active peptides, potentiate the central stimulatory effects of NA and depressant action of acetylcholine as have been shown by the authors previously. The aim of the work has been to study the effects of these peptides on the central action of 5-HT. For experiments female Wistar rats were used. 5-HT given ivc to the animals and 5-HTP applied ip resulted in an increase of the pain threshold to the electrical stimuli and in a worse motor coordination. Bradykinin injected ivc or kallikrein ip to some extent abolished these effects. The biochemical tests revealed that bradykinin ivc lead to a significant decrease in 5-HT content in the midbrain. In experiments in vitro this peptide increased markedly the release of the platelets 5-HT and inhibited the uptake of this mediator to platelets. The results have shown that kinins can attenuate the central action of 5-HT. This effect can be ascribed, at least in part to a kinin-induced changes of 5-HT concentration in some structures of the central nervous system.
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PMID:Effect of kinins on the central action of serotonin. 108 29

A method has been developed to measure the analgesic action of aspirin-like drugs in knee joints of anaesthetized dogs. Bradykinin, injected into the joint cavity, induced a reflex rise in blood pressure which was dose-dependent; this was used as a measure of nociceptive activity. The joint cavity became more sensitive to bradykinin as the experiment proceeded, or when a low concentration of prostaglandin E1 or E2 was infused locally. The increase in sensitivity with time was prevented by local injection of aspirin or indomethacin, but that induced by exogenous prostaglandin infusion was not. Injections of carrageenin into dog knee joints increased the prostaglandin E2 content of synovial fluid by up to 160 ng per joint; indomethacin prevented this increase. These experiments support our previous conclusion that local biosynthesis of a prostaglandin (induced by mild trauma) sensitizes pain receptors to mechanical or chemical stimuli. Aspirin-like drugs are analgesic because they prevent prostaglandin biosynthesis, thereby preventing this sensitization.
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PMID:Inhibition of prostaglandin biosynthesis as the mechanism of analgesia of aspirin-like drugs in the dog knee joint. 114 92

Nasal insufflation with bradykinin induces nasal discomfort, rhinorrhea, and nasal blockage, all features of rhinitis. We recently showed these effects to be mediated by the B2-receptor subtype, which has been identified at neural and vascular sites. To investigate the relative contribution of capsaicin-sensitive sensory neural stimulation to the action(s) of bradykinin, two randomized double-blind placebo-controlled studies have been undertaken comparing the nasal effects of single-dose administrations of bradykinin (1.88 x 10(-3) M) and capsaicin (3.28 x 10(-5) M). In comparison with placebo, both bradykinin and capsaicin induced nasal pain/discomfort (P less than 0.01) and rhinorrhea (P less than 0.02). Bradykinin significantly increased nasal airways resistance (P less than 0.005) and plasma protein exudation (P less than 0.02). No such changes were identified after nasal challenge with capsaicin. These findings suggest that bradykinin-induced nasal discomfort and rhinorrhea are neurally mediated, whereas the effects on nasal airways resistance and plasma protein exudation are due to a direct vascular action. In addition, these findings question the role of capsaicin-sensitive sensory neurons in nasal vasculature responses, because no vascular effects of capsaicin could be identified in the human nasal mucosa.
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PMID:Nasal effects of bradykinin and capsaicin: influence on plasma protein leakage and role of sensory neurons. 131 73

The endogenous peptide bradykinin is found in plasma and inflammatory exudates and has been implicated as a chemical mediator of inflammatory pain and hyperalgesia. Two subtypes of bradykinin receptors, B1 and B2, have been described, and antagonists for the receptor subtypes have been synthesized. The bradykinin analogs [desArg9,Leu8]BK and DArg[Hyp3,DPhe7]BK have been reported to have antagonist activity at the B1 and B2 bradykinin receptors in smooth muscle, respectively. Behavioral studies in rats indicate that the bradykinin analogs can block the algesic effects of bradykinin. We wished to determine the effects of bradykinin and the bradykinin analogs (B1 and B2 analogs, respectively) on cutaneous nociceptors in the monkey. In addition, we wished to determine the type of bradykinin receptor that mediates the sensitizing effects of bradykinin. Recordings were made from single C-fiber and A-fiber nociceptive afferents (CMHs and AMHs) that innervated hairy skin. Heat sensitivity before and after the injections was determined with a heat test sequence consisting of stimuli that ranged, in 1 degree C increments, from 41 degrees to 49 degrees C. Intradermal injections of vehicle (neutral normal saline) failed to alter the heat response of CMHs. Bradykinin (10 nmol in 10 microliters) evoked activity in 6 of 10 CMHs and sensitized all the fibers to heat stimuli. After the bradykinin injection, the mean heat threshold of the CMHs decreased from 44 +/- 0.5 degrees to 42.7 +/- 0.5 degrees C (mean +/- SEM, p less than 0.02), and the total response to the heat test sequence increased by 87% (p less than 0.002). In a related psychophysical study in human volunteers, the same dose of bradykinin resulted in a comparable (115%) increase in ratings of pain (Manning et al., 1991). Bradykinin also evoked activity in 10 of 17 AMHs and sensitized 8 AMHs to heat stimuli. Bradykinin failed to alter the threshold for activation of CMHs to mechanical stimuli as measured by application of von Frey hairs to the receptive field. In contrast to bradykinin, intradermal injection of the B1 and B2 analogs (10 nmol in 10 microliters) evoked activity in 2 of 6 and 0 of 5 CMHs, respectively. A noteworthy finding was that both analogs enhanced the response of CMHs to heat stimuli by 50% (B1 analog, 1.5 +/- 0.1; B2 analog, 1.5 +/- 0.2). The B1 (n = 10) and B2 (n = 5) analogs did not evoke activity in any of the 15 AMHs tested.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effects of bradykinin and sequence-related analogs on the response properties of cutaneous nociceptors in monkeys. 132 2

1. Bradykinin is considered to be an important mediator of pain and hyperalgesia associated with injury and inflammation. Psychophysical studies were conducted in a patient with complete kininogen deficiency to determine whether the absence of bradykinin was associated with abnormalities in pain sensibility. Pain evoked by heat stimuli to the thenar eminence was tested before and after a localized burn, which has been shown to cause hyperalgesia in normal subjects. In addition, pain evoked by intradermal administration of bradykinin (0.1-10 micrograms) to the forearm and the effects of bradykinin on pain induced by heat stimuli were studied. The patient rated the intensity of pain evoked by all heat stimuli relative to the pain induced by a 3 s 45 degrees C stimulus. 2. The patient's heat pain threshold (45 degrees C) in the glabrous skin was similar to that of age-matched control subjects (n = 5) and to that previously observed in younger control subjects. 3. The burn resulted in a decrease in pain threshold and an increase in pain induced by suprathreshold stimuli. The magnitude of hyperalgesia was within the range observed in the age-matched control subjects and in younger control subjects. Thus, kinins are not essential for the development of hyperalgesia after heat injury. 4. In control subjects, intradermal injections of bradykinin produced pain and hyperalgesia to heat stimuli. In the patient, intradermal bradykinin injections induced minimal pain and no hyperalgesia to heat stimuli. Thus, congenital absence of kininogens may be associated with a deficiency in bradykinin receptors.
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PMID:Role of kinins in pain and hyperalgesia: psychophysical studies in a patient with kininogen deficiency. 132 52

The local motor response to bradykinin and the bacterial chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP) was investigated in the guinea-pig isolated renal pelvis and ureter in relation to possible activation of capsaicin-sensitive primary afferent nerves and release of sensory neuropeptides. Both bradykinin (1 nM-10 microM) and FMLP (10 nM-10 microM) produced a concentration-dependent positive inotropic effect in the isolated renal pelvis which was unaffected by in vitro capsaicin desensitization. The response to bradykinin was antagonized by HOE 140, a bradykinin receptor antagonist, while it was unaffected by MEN 10,376, a tachykinin receptor antagonist, hCGRP(8-37) a calcitonin gene-related peptide (CGRP) receptor antagonist and N-t-BOC-Phe-DLeu-Phe-DLeu-Phe (BPLPLP), an FMLP antagonist. The response to FMLP was blocked by BPLPLP while it was unaffected by HOE 140, MEN 10,376 or hCGRP(8-37). Indomethacin (10 microM) enhanced the response to both bradykinin and FMLP. Bradykinin transiently activated rhythmic contractions in the isolated ureter. The response to bradykinin was blocked by HOE 140 and was unaffected by in vitro capsaicin desensitization, indomethacin, MEN 10,376 or BPLPLP. FMLP had no motor effect on the resting ureter but when rhythmic background contractions were evoked by the addition of 100 nM endothelin 1, it produced a transient suppression of ureteral motility. This inhibitory effect was unchanged by in vitro capsaicin desensitization or HOE 140 while it was abolished by indomethacin or BPLPLP pretreatment. Both bradykinin and FMLP evoked the release of CGRP-like immunoreactivity in the renal pelvis. The effect of bradykinin but not that of FMLP was abolished by indomethacin. By contrast neither bradykinin nor FMLP did evoke a significant CGRP-LI release in the ureter. It is concluded that bradykinin and FMLP affect pyeloureteral motility through specific and independent pathways. The local motor responses produced by these chemical stimulants are independent from the release of sensory neuropeptides from capsaicin-sensitive primary afferent neurons. Direct neurochemical evidence was obtained for activation of capsaicin-sensitive primary afferents in the renal pelvis: such a mechanism could be involved in the genesis of ureteral pain whenever bradykinin or FMLP come into contact with sensory nerves in the pyeloureteral wall.
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PMID:Local motor responses to bradykinin and bacterial chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP) in the guinea-pig isolated renal pelvis and ureter. 133 50


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