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)

Response properties of nociceptors in the rat's temporomandibular joint (TMJ) were investigated using an in vitro TMJ-nerve preparation. Recordings were obtained from 33 nociceptive units that responded to mechanical, chemical, and/or thermal stimuli. According to both characteristics of nociceptors and afferent fibers, nociceptive units in the TMJ area were classified into the following four subtypes: Adelta-high-threshold mechanonociceptor (HTM) (12.1%), Adelta-polymodal nociceptor (POLY) (36.4%), C-HTM (12.1%), and C-POLY (39.4%). The mean mechanical threshold of the Adelta units was significantly lower than that of the C units. Bradykinin increased the discharge of Adelta- and C-POLY units. No significant differences of thermal thresholds between Adelta and C units were found. The percentage of Adelta units was 47.2% and of C units was 52.8%, respectively. In the TMJ area, POLY units were predominant (75.8%), suggesting that inflammatory reactions can easily evoke pain sensation.
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PMID:Subtypes of nociceptive units in the rat temporomandibular joint. 1451 57

Bradykinin has been implicated in the pathogenesis of inflammatory arthritis by virtue of the potent pro-inflammatory properties. The purpose of this study is to investigate the expression of bradykinin in patients with internal derangement of the temporomandibular joint (TMJ). We examined 33 TMJ synovial biopsy specimens from 31 patients with internal derangement of the TMJ by an immunohistochemical technique using specific antibodies. We also determined the concentration of bradykinin in 20 synovial fluids from 18 patients with TMJ internal derangement by enzyme-linked immunosorbent assay. These data were compared with those of the control subjects. Bradykinin was predominantly localized in the synovial lining cell layer of TMJ samples obtained from patients with TMJ internal derangement. Bradykinin was also detected in 19 patients' TMJ synovial fluids and the average of bradykinin concentration in the synovial fluids of patients was higher than that of the healthy controls. Although a statistically significant correlation was not observed, these findings support the hypothesis that bradykinin may also be involved in the pathogenesis of TMJ pain and synovitis.
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PMID:Bradykinin expression in synovial tissues and synovial fluids obtained from patients with internal derangement of the temporomandibular joint. 1462 Jun 99

Bradykinin-induced mechanical hyperalgesia is sympathetically dependent and B(2)-type bradykinin receptor-mediated in the rat; however, a sympathetically independent component of bradykinin hyperalgesia is shown after subdiaphragmatic vagotomy. We evaluated the mechanism of this bradykinin-induced sympathetic-independent mechanical hyperalgesia. The dose-response curve for bradykinin mechanical hyperalgesia in sympathectomized plus vagotomized rats was similar in magnitude to that for sympathetically dependent bradykinin hyperalgesia in normal rats. Although bradykinin mechanical hyperalgesia was mediated by the B(2)-type bradykinin receptors after sympathectomy plus vagotomy, it had a much more rapid latency to onset. This hyperalgesia was significantly attenuated by inhibition of protein kinase A but not protein kinase C, similar to the hyperalgesia produced by prostaglandin E(2), an agent that directly sensitizes primary afferent nociceptors. However, unlike prostaglandin E(2)-induced mechanical hyperalgesia in normal rats, after sympathectomy plus vagotomy, bradykinin-induced hyperalgesia was not attenuated by inhibition of nitric oxide synthesis. Peripheral administration of a mu opioid agonist, [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin, significantly attenuated bradykinin mechanical hyperalgesia after sympathectomy plus vagotomy. These data suggest that after sympathectomy plus subdiaphragmatic vagotomy, bradykinin acts directly on primary afferents to produce mechanical hyperalgesia via a novel protein kinase A-dependent signaling mechanism.
J Pain 2002 Oct
PMID:Sympathetic-independent bradykinin mechanical hyperalgesia induced by subdiaphragmatic vagotomy in the rat. 1462 40

Bradykinin (BK) is well known as a potent mediator of pain and hyperalgesia. Using a highly sensitive nociception test, we found that intraplantar (i.pl.) injection of BK produced nociceptive hyper-responses in partial sciatic nerve-injured mice, compared with the control sham-operated animals. By use of selective agonists and antagonists, we revealed that BK nociception in sham-operated mice was mediated through B2 receptor, whereas that in injured mice was mediated through B1 receptor. When we examined the activation of extracellular signal-regulated protein kinase (ERK) in dorsal root ganglion (DRG) neurons upon i.pl. injection of BK, phosphorylated ERK was mainly observed in unmyelinated neurons in sham-operated mice, and in case of nerve-injured mice, ERK was mainly activated in myelinated neurons and satellite cells. The B1 receptor agonist, [Lys-des-Arg(9)]-BK also produced nociceptive response and activated ERK only in nerve-injured mice. BK or B1 agonist-induced activation of ERK in DRG neurons of nerve-injured mice was completely blocked by pretreatment with antisense oligodeoxynucleotide (AS-ODN) for B1 receptor. We found that in sham-operated mice mainly B2 receptors were expressed in unmyelinated DRG neurons with a very little presence of B1 receptor. After nerve injury, B2 receptor expression drastically decreased, whereas B1 receptors were newly expressed mainly in myelinated DRG neurons and satellite cells. Finally, BK nociception in sham-operated mice was blocked by AS-ODN for B2 receptors and that in injured mice by AS-ODN for B1 receptors. Altogether, these findings confirm a switching of receptor and fiber subtype for BK nociception after peripheral nerve injury, which might contribute to the pathobiology of neuropathic pain.
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PMID:Switching of bradykinin-mediated nociception following partial sciatic nerve injury in mice. 1463 40

Six members of the mammalian transient receptor potential (TRP) ion channels respond to varied temperature thresholds. The natural compounds capsaicin and menthol activate noxious heat-sensitive TRPV1 and cold-sensitive TRPM8, respectively. The burning and cooling perception of capsaicin and menthol demonstrate that these ion channels mediate thermosensation. We show that, in addition to noxious cold, pungent natural compounds present in cinnamon oil, wintergreen oil, clove oil, mustard oil, and ginger all activate TRPA1 (ANKTM1). Bradykinin, an inflammatory peptide acting through its G protein-coupled receptor, also activates TRPA1. We further show that phospholipase C is an important signaling component for TRPA1 activation. Cinnamaldehyde, the most specific TRPA1 activator, excites a subset of sensory neurons highly enriched in cold-sensitive neurons and elicits nociceptive behavior in mice. Collectively, these data demonstrate that TRPA1 activation elicits a painful sensation and provide a potential molecular model for why noxious cold can paradoxically be perceived as burning pain.
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PMID:Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. 1504 18

Bradykinin B1 and B2 receptors contribute to nociceptor sensitization under inflammatory conditions. Here, we examined the vascular inflammatory responses and nociceptive effects resulting from activation of B1 and B2 receptors in healthy and UV-B irradiated skin in human volunteers. The B1 receptor agonist des-Arg(10)-Kallidin (10(-6)-10(-3)M) and the B2 receptor agonist bradykinin (10(-9)-10(-4)M) were administered by dermal microdialysis to the ventral thigh. UV-B irradiation was performed 24 h prior to the experiment with the threefold minimum erythemal dose. Pain sensation perceived during the stimulation with the bradykinin receptor agonists was estimated on a numeric scale. Local and axon reflex-induced vasodilations were recorded by laser Doppler imaging. For protein extravasation, total protein content in the dialysate was assessed as a measure of increased endothelial permeability. In normal skin, both B1 and B2 receptor activation dose-dependently evoked pain, vasodilatation and protein extravasation. In UV-B irradiated skin, pain sensation and axon reflex vasodilatation were enhanced by both B1 and B2 agonists, whereas local vasodilatation was increased only following B1 receptor activation. The UV-B irradiation did not enhance B1 and B2 receptor-induced protein extravasation indicating a differential sensitization of the neuronal, but not the vascular response.
Pain 2004 Jul
PMID:Sensitization to bradykinin B1 and B2 receptor activation in UV-B irradiated human skin. 1527 68

The awareness in specific brain centers of angina pectoris most often results from ischemic episodes in the heart. These ischemic episodes induce the release of a collage of chemicals that activate chemosensitive and mechanoreceptive receptors in the heart, which in turn excite receptors of the sympathetic afferent pathways. Ascending pain signals from these fibers result in the activation of the brain centers which are involved in the perception and integration of cardiac pain. Cytochemical studies of the nervous system provide the opportunity to identify these areas at the cellular level. In the present investigation, cardiac nociception was studied in the brains and the spinal cords of rats, using Fos protein as a marker of neuronal activation, following the application of pain-inducing chemicals to the heart. Induction of myocardial pain in conscious rats was achieved by infusion of bradykinin (0.5 microg) or capsaicin (5 microg) into the pericardial sac. During pain stimulation, the rats demonstrated pain behavior, in conjunction with alterations in heart rate and blood pressure. The cerebral Fos expression pattern was studied 2 h after pain stimulation. In contrast to the control group, increased Fos expression was found following the use of both capsaicin and bradykinin in a variety of areas of the brain. Bradykinin, but not capsaicin, induced Fos expression in the upper thoracic and upper cervical spinal cord; these segments are the sites where cardiac sympathetic fibers terminate. This finding suggests that these two chemicals use two different pathways, and provides extra evidence for the role of the vagus nerve in the transmission of cardiac nociception. Different cerebral areas showed an increase in the c-fos activity following pericardial application of pain-inducing chemicals. The role of these cerebral areas in the integration of cardiac pain is discussed in relation to the identified pathways which transmit cardiac pain.
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PMID:An integrated study of heart pain and behavior in freely moving rats (using fos as a marker for neuronal activation). 1530 89

Bradykinin (BK) has long been recognized as an important mediator of pain and inflammation. In normal tissue bradykinin causes an acute sensation of pain by an action at B2 receptors, but in inflamed tissue the pharmacology of the response changes to that of B1 receptors. Attempts to demonstrate the presence of functional B1 receptors in sensory neurones have failed, however, and the actions of B1 agonists have therefore been presumed to be indirect. Here we show that specific B1 receptor activation causes translocation of the epsilon isoform of protein kinase C (PKC-epsilon) to the membrane of a small fraction of freshly isolated sensory neurones from rats and mice. The proportion of neurones in which PKC-epsilon translocation was observed increased to around 20% of neurones after 3 days in culture with the neurotrophins glial cell line derived neurotrophic factor (GDNF) and neurturin, but not with nerve growth factor (NGF). Using in situ hybridization we found that the proportion of neurones expressing B1 mRNA increased from close to zero to 20.4% after 8 h culture in GDNF. Neurones expressing functional B1 receptors were negative for the neuropeptides CGRP and substance P, but most expressed functional TRPV1 receptors for capsaicin (60%) and bound the lectin IB4 (68%), both markers characteristic of nociceptors. B1 activation enhanced the heat-activated membrane current approximately 3-fold, and the enhancement was much more prolonged than was the case with B2 activation, consistent with a role for B1 receptors in sustained pain. We conclude that GDNF and neurturin potently upregulate functional B1 receptor expression in small non-peptidergic nociceptive neurones.
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PMID:Functional bradykinin B1 receptors are expressed in nociceptive neurones and are upregulated by the neurotrophin GDNF. 1531 21

Bradykinin, an endogenous nonapeptide and an important mediator of inflammation, is also implicated in the initiation and maintenance of pain. Both des-Arg(8), Leu(8)-bradykinin (dALBK) and HOE-140, the prototypic bradykinin B1 and B2 receptor antagonists, respectively, have been shown to reduce pain behaviors and inflammation in animal models of persistent nociception. We studied them for activity against incision-induced pain behaviors in a rat model for postoperative pain. A 1-cm plantar incision was made in the hind paw of halothane-anesthetized rats and closed with 5-0 nylon. Withdrawal responses to punctate and nonpunctate mechanical stimuli were tested with von Frey filaments and a plastic disk attached to a von Frey filament, respectively. Withdrawal latency to radiant heat was also tested. Rats were tested 1 day before the incision, 1 h after the incision, and 0.5, 1, 1.5, and 2.5 h after the injection of the drug. They were then retested at the same times before and after the injection of the drug on each of the first 2 postoperative days. The rats received the saline vehicle dALBK (0.1, 0.3, 1.0, or 3.0 mg/kg) or HOE-140 (0.1, 0.3, 1.0, or 3.0 mg/kg) IV. Another group of rats had the drug injected 1 h before incision and tested as above. Statistical significance (P < 0.05) was determined with Kruskal-Wallis test and a two-way analysis of variance. None of the doses of either dALBK or HOE-140 affected the responses to punctate or blunt mechanical stimulation or heat, either as a pretreatment or as a posttreatment. These data support the unique mechanisms for incision-induced pain relative to inflammation-related pain. Although inflammation may represent a component of incisional pain, the etiology of inflammation and its role seem different than in other models.
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PMID:Bradykinin antagonists have no analgesic effect on incisional pain. 1538 70

Bradykinin (BK) excites dorsal root ganglion cells, leading to the sensation of pain. The actions of BK are thought to be mediated by heterotrimeric G protein-regulated pathways. Indeed there is strong evidence that in different cell types BK is involved in phosphoinositide breakdown following activation of G(q/11). In the present study we show that the Ca(2+) current flowing through L-type voltage-gated Ca(2+) channels in NG108-15 cells (differentiated in vitro to acquire a neuronal phenotype), measured using the whole-cell patch clamp configuration, is reversibly inhibited by BK in a voltage-independent fashion, suggesting a cascade process where a second messenger system is involved. This inhibitory action of BK is mimicked by the application of 1,2-oleoyl-acetyl glycerol (OAG), an analog of diacylglycerol that activates PKC. Interestingly, OAG occluded the effects of BK and both effects were blocked by selective PKC inhibitors. The down modulation of single L-type Ca(2+) channels by BK and OAG was also investigated in cell-attached patches. Our results indicate that the inhibitory action of BK involves activation of PKC and mainly shows up in a significant reduction of the probability of channel opening, caused by an increase and clustering of null sweeps in response to BK.
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PMID:L-type calcium channel gating is modulated by bradykinin with a PKC-dependent mechanism in NG108-15 cells. 1553 63


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