Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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. Properties of sensory receptors with slowly conducting nerve fibers (less than 10 m/s) were studied using a rat skin-saphenous nerve in vitro preparation where receptive fields of identified single units can be isolated and superfused at the corium side with defined chemical solutions. 2. With mechanical search stimuli, 150 slowly adapting units were identified, 88% C-fibers, and the remainder, A delta-fibers. The majority of these units (65%) were categorized as mechano-heat sensitive ("polymodal") with controlled radiant heat stimulation. The remaining units were classified as low- or high-threshold mechanoreceptors according to their von Frey thresholds. 3. Bradykinin (BK), in concentrations of 10(-8) to 10(-4) M, was repeatedly applied for 1 min at 10-min intervals. Fifty-six percent of the polymodal C-fibers responded to BK (up to 10(-5) M), in contrast to 17% of the heat-insensitive units (P less than 0.01). No correlation between BK sensitivity and conduction velocity or von Frey threshold was found. 4. The BK "threshold concentrations" to excite C- and A delta-fibers were about equally distributed over a range from 10(-8) to 10(-5) M. 5. There was a large interindividual variability in pattern and magnitude of the response to BK. Intraindividually, a marked tachyphylaxis upon repeated BK stimulation was observed. 6. In fibers with a slow development of tachyphylaxis, the effects of conditioning application of different chemicals on BK responsiveness were studied. Norepinephrine in 10(-7) M concentration did not produce a significant effect, whereas 10(-5) M and 10(-4) M seemed to increase the BK responses. 7. Prostaglandin E2 (10(-6) M) caused a weak sensitization to BK on average (n.s.), but serotonin (10(-6) M) was clearly effective (P less than 0.05). 8. The strongest sensitization to BK (P = 0.01) resulted from conditioning heat stimulation, which also uncovered a responsiveness in some units initially insensitive to BK. 9. In some experiments the calcium concentration in the superfusate of receptive fields was lowered to 0.3 mM, which induced ongoing activity in C-fibers and markedly increased the BK responses in two polymodal units tested. Increasing the calcium concentration to 3.0 mM reversed these effects. 10. After completing the BK test protocol, polymodal C-fibers were exposed to other chemicals.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chemosensitivity of fine afferents from rat skin in vitro. 234 84

Characteristics of the polymodal receptor were studied using in vitro testis superior spermatic nerve preparations excised from anesthetized dogs. They were in most aspects similar to those reported previously using in vivo preparations. The majority (90%) of the tested polymodal units had small myelinated nerve fibers; the rest had nonmyelinated fibers. The mean mechanical threshold as determined by von Frey hairs was 17.5 g/mm2 (n = 476). There was a tendency for a unit with a higher conduction velocity to have a lower mechanical threshold. Bradykinin and hypertonic saline consistently caused a dose-dependent increase in discharge rate of these units; high K+ solution was also found to be a consistent stimulant. The responses of C-fiber receptors were not significantly different from those of A-delta-fibers. Heat stimulation up to 50 degrees C evoked discharges in 99 out of the total 103 units tested. The mean threshold temperature was 44.4 degrees C for the first trial. In 19 units in which the same heat stimulation was tested after an interval of 10 min, 10 units showed sensitization; 3 units were deactivated; and no clear difference was observed in the rest. No unit responded with a substantial increase in discharge rate to cold stimuli of 20 degrees C or less. A small temperature rise of 2 degrees C from the normal surface temperature of the testis (34 degrees C) significantly increased the response to hypertonic saline (616 mM) (2.41 +/- 0.22 impulses/s at 34 degrees C to 3.23 +/- 0.44 impulses/s at 36 degrees C) and to bradykinin (9 X 10(-8) M) (1.95 +/- 0.35 impulses/s at 34 degrees C to 2.85 +/- 0.19 impulses/s at 36 degrees C). The majority of the units recorded from the superior spermatic nerve in this experiment were most probably of polymodal receptor type, although the heat response was tested in a limited number of units. A very small number of a different type of receptor was discovered: rapidly adapting mechano-receptors, which responded almost exclusively to mechanical stimulation and were especially sensitive to a light mechanical stimulus moving across the receptive fields. The response properties of receptors studied in vitro remained practically unchanged during the experiments of several hours. The present experiments have shown that this preparation is suitable for systematic investigations, especially of the effects of chemical agents, on the polymodal receptor, which plays important roles in nociceptive functions.
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PMID:Response properties of polymodal receptors studied using in vitro testis superior spermatic nerve preparations of dogs. 355 98

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

The effects of trinitrobenzene sulfonic acid (TNBS)-induced inflammation on specialized, low-threshold, slowly adapting rectal mechanoreceptors were investigated in the guinea pig. Under isoflurane anesthesia, 300 microl saline or TNBS (15 mg/ml) in 30% ethanol was instilled 7 cm from the anal sphincter. Six or 30 days later, single unit extracellular recordings were made from rectal nerve trunks in flat-sheet in vitro preparations attached to a mechanical tissue stretcher. TNBS treatment caused macroscopic ulceration of the rectal mucosa at 6 days, which fully resolved by 30 days. Muscle contractility was unaffected by TNBS treatment. At 6 days posttreatment, responses of low-threshold rectal mechanoreceptors to circumferential stretch were increased, and the proportion of afferents responding with von Frey hair thresholds <or=0.1 mN and mechanoreceptor excitability in response to electrical stimulation were increased in TNBS-treated tissue, suggesting increased sensitivity of the mechanotransducer. Mechanoreceptor function at 30 days posttreatment was in most cases unchanged. The inflammatory mediator prostaglandin E(2) (1 microM) activated mechanoreceptors (6 days) in conjunction with contractile activity, but capsaicin (1 microM) failed to activate mechanoreceptors. Bradykinin (1 microM) activated mechanoreceptors independently of contractile activity and responses to stretch were increased in the presence of bradykinin. Both capsaicin and bradykinin activated unidentified stretch-insensitive afferents independently of contractile activity. Mechanoreceptor function is modulated at 6 days posttreatment but not at 30 days, suggesting a moderate increase in mechanoreceptor sensitivity in inflamed tissue but not after recovery. Other unclassified stretch-insensitive afferents are responsive to inflammatory mediators and capsaicin and may be involved in aspects of visceral sensation.
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PMID:TNBS-induced inflammation modulates the function of one class of low-threshold rectal mechanoreceptors in the guinea pig. 1875 10