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Jon D. Levine - One of the best experts on this subject based on the ideXlab platform.
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sexual dimorphism in the effect of nonhabituating stress on neurogenic Plasma Extravasation
European Journal of Neuroscience, 2005Co-Authors: Paul Green, Jon D. LevineAbstract:The sympathoadrenal axis contributes to the sexual dimorphism of the inflammatory response. As stress both activates the sympathoadrenal axis and profoundly affects inflammation and inflammatory disease, we evaluated whether stress exerts a sexually dimorphic effect on a major component of the inflammatory response, Plasma Extravasation. We evaluated the effect of a nonhabituating stress, repeated intermittent sound (30 min/day for 4 days), on neurogenic synovial Plasma Extravasation, induced by bradykinin in the rat knee joint. Sound stress profoundly inhibited bradykinin-induced Plasma Extravasation in male rats, but profoundly enhanced it in female rats. These effects took 24 h to fully develop after the last exposure to stress. In gonadectomized males, bradykinin-induced Plasma Extravasation was lower than intact males, and sound stress now enhanced it, i.e. gonadectomized males were phenotypically like intact females. In gonadectomized females, bradykinin-induced Plasma Extravasation was greater than in intact adult females, and sound stress still enhanced it. Adrenal enucleation significantly attenuated the effect of sound stress on bradykinin-induced Plasma Extravasation in both male and female rats. We tested the hypothesis that these effects of sound stress were due to sustained enhanced Plasma levels of stress hormones. Corticosterone and epinephrine, only when administered in combination, over five days, produced a qualitatively similar effect as sound stress, i.e. bradykinin-induced Plasma Extravasation was significantly decreased in males and increased in females. These findings suggest that a combined effect of the hypothalamic-pituitary adrenal and sympathoadrenal stress axes are responsible for the marked sexual dimorphism in the effect of stress on the inflammatory response.
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repeated non habituating stress suppresses inflammatory Plasma Extravasation by a novel sympathoadrenal dependent mechanism
European Journal of Neuroscience, 2003Co-Authors: Holly J Strausbaugh, Mary F Dallman, Paul G Green, Jon D. LevineAbstract:The mechanism by which chronic stress affects the course of inflammatory diseases is still not well understood. We have evaluated the effect of two types of nonhabituating stress on a major component of the inflammatory response, synovial Plasma Extravasation, induced by perfusion of the potent inflammatory mediator, bradykinin and evaluated the underlying neuroendocrine mechanism in the rat. Chronic intermittent noise or ether stress induced profound inhibition of bradykinin-induced Plasma Extravasation, which is associated with increased adjuvant-arthritis severity. This inhibition, however, took 24 h to fully develop after the last exposure to stress and persisted for at least 48 h. The inhibition could be reversed by an additional exposure to the stressor, just prior to measuring the inflammatory response, suggesting that the delay is due to stress-induced release of a factor that acutely masks the inhibition of the inflammatory response. This novel, unexpected feature of the effect of nonhabituating stress on inflammation may help explain variability in effects of stress in patients with inflammatory disease. The effect of nonhabituating stress on inflammation was dependent on the sympathoadrenal axis with no detectable contribution by the hypothalamic-pituitary-adrenal axis.
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repeated but not acute stress suppresses inflammatory Plasma Extravasation
Proceedings of the National Academy of Sciences of the United States of America, 1999Co-Authors: Holly J Strausbaugh, Mary F Dallman, Jon D. LevineAbstract:Clinical findings suggest that inflammatory disease symptoms are aggravated by ongoing, repeated stress, but not by acute stress. We hypothesized that, compared with single acute stressors, chronic repeated stress may engage different physiological mechanisms that exert qualitatively different effects on the inflammatory response. Because inhibition of Plasma Extravasation, a critical component of the inflammatory response, has been associated with increased disease severity in experimental arthritis, we tested for a potential repeated stress-induced inhibition of Plasma Extravasation. Repeated, but not single, exposures to restraint stress produced a profound inhibition of bradykinin-induced synovial Plasma Extravasation in the rat. Experiments examining the mechanism of inhibition showed that the effect of repeated stress was blocked by adrenalectomy, but not by adrenal medullae denervation, suggesting that the adrenal cortex mediates this effect. Consistent with known effects of stress and with mediation by the adrenal cortex, restraint stress evoked repeated transient elevations of Plasma corticosterone levels. This elevated corticosterone was necessary and sufficient to produce inhibition of Plasma Extravasation because the stress-induced inhibition was blocked by preventing corticosterone synthesis and, conversely, induction of repeated transient elevations in Plasma corticosterone levels mimicked the effects of repeated stress. These data suggest that repetition of a mild stressor can induce changes in the physiological state of the animal that enable a previously innocuous stressor to inhibit the inflammatory response. These findings provide a potential explanation for the clinical association between repeated stress and aggravation of inflammatory disease symptoms and provide a model for study of the biological mechanisms underlying the stress-induced aggravation of chronic inflammatory diseases.
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Neural and Endocrine Mechanisms Mediating Noxious Stimulus-Induced Inhibition of Bradykinin Plasma Extravasation in the Rat
The Journal of pharmacology and experimental therapeutics, 1999Co-Authors: Frederick Jia-pei Miao, Jon D. LevineAbstract:We studied the mechanisms by which activation of primary afferent nociceptors inhibits bradykinin-induced Plasma Extravasation in the rat. First, capsaicin, administered into the plantar surface of the hindpaw, dose-dependently inhibited bradykinin-induced Plasma Extravasation in the knee joint, a site distant from the noxious stimulus. The inhibitory effect of capsaicin was markedly attenuated after T12/L1 spinal transection combined with lumbar preganglionic sympathectomy, which interrupts ascending spinal tracts to rostral sites and to spinal sympathetic and sympathoadrenal outflow. Second, interruption of the sympathetics (cutting the L1-3 white rami) or surgical adrenal denervation significantly attenuated capsaicin-induced inhibition of bradykinin-induced Plasma Extravasation. Interruption of the sympathoadrenal pathway produced the largest attenuation. Lesioning of the hypothalamic-pituitary-adrenal axis did not affect the inhibitory action of capsaicin. Third, intra-articular perfusion with phentolamine (10−5 M, an α-adrenoceptor antagonist), propranolol (10−5 M, a β-adrenoceptor antagonist), and naloxone (10−5 M, an opioidergic receptor antagonist) each attenuated the inhibitory action of capsaicin. Propranolol and naloxone produced the largest attenuation. Blocking glucocorticoid receptors (RU-38,486, 30 mg/kg s.c.) did not affect the inhibitory action of intraplantar capsaicin. Fourth, the magnitude of the attenuation of capsaicin-induced inhibition of bradykinin-induced Plasma Extravasation after a combined treatment of surgical lumbar sympathetic decentralization with intra-articular phentolamine or surgical adrenal denervation with intra-articular propranolol or naloxone was similar to each of the surgical or pharmacological treatments of the same axis alone. These results support the suggestion that two neural/endocrine circuits, sympathoadrenal and sympathetic, account for most, if not all, of nociceptor activity-induced inhibition of bradykinin-induced Plasma Extravasation produced by capsaicin.
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inhibition of bradykinin induced Plasma Extravasation produced by noxious cutaneous and visceral stimuli and its modulation by vagal activity
Journal of Neurophysiology, 1997Co-Authors: Frederick Jia-pei Miao, W. Janig, Paul Green, Jon D. LevineAbstract:Miao, Frederick Jia-Pei, Wilfrid Janig, Paul G. Green, and Jon D. Levine. Inhibition of bradykinin-induced Plasma Extravasation produced by noxious cutaneous and visceral stimuli and its modulation...
Susan D Brain - One of the best experts on this subject based on the ideXlab platform.
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involvement of vanilloid receptors and purinoceptors in the phoneutria nigriventer spider venom induced Plasma Extravasation in rat skin
European Journal of Pharmacology, 2000Co-Authors: Soraia K P Costa, G De Nucci, Edson Antunes, Susan D BrainAbstract:Abstract Phoneutria nigriventer venom causes stimulation of capsaicin-sensitive primary afferent neurons in the rat dorsal skin, leading to neurogenic Plasma protein Extravasation due to the release of tachykinin NK1 receptor agonist. In this study we further investigated the mechanisms involved in the venom-induced activation of capsaicin-sensitive primary afferent neurons. The Plasma Extravasation in response to venom intradermally injected was measured in Wistar rats as the local accumulation of i.v. injected 125I-labelled human serum albumin into skin sites. The tachykinin NK1 receptor agonist, d -Ala-[ l -Pro9,Me-Leu8]substance P-(7–11) (GR73632; 10–100 pmol/site), induced a significant Plasma leakage that was abolished by the selective tachykinin NK1 receptor antagonist, (S)-1-[2-[3-(3,4-dichlorphenyl)-1 (3-isopropoxyphenylacetyl) piperidin-3-yl] ethyl]-4-phenyl-1 azaniabicyclo [2.2.2]octane chloride (SR140333; 1 nmol/site), whereas the leakage after venom (1–10 μg/site) was significantly inhibited (but not abolished) by SR140333. The calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP-(8–37), failed to further reduce the residual Plasma Extravasation induced by venom plus SR140333. The μ-opioid receptor agonist, [ d -Ala2,Me-Phe4,Gly-ol5]enkephalin (DAMGO), and the local anaesthetic, lignocaine, had no effect on the venom-induced Plasma Extravasation. Similarly, the L-, N- and P/Q-type voltage-sensitive Ca2+ channel blockers (verapamil, ω-conotoxin MVIIA and MVIIC, respectively) as well as the Na+ channel blockers, tetrodotoxin and carbamazepine, had no effect on the venom-induced effect. Neither the systemic treatment nor the local injection of ruthenium red prevented the venom-induced Plasma Extravasation. However, the vanilloid receptor antagonist, N-[2-(4-chlorophenyl) ethyl]-1,3,4,5-tetrahydro-7,8-dihydroxy-2H-2-benzazepine-2-carbothioamide (capsazepine; 120 μmol/kg, i.v.), reduced by 48% (P
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neurogenic cutaneous vasodilatation and Plasma Extravasation in diabetic rats effect of insulin and nerve growth factor
British Journal of Pharmacology, 1998Co-Authors: Gavin S Bennett, Susan D Brain, Neil E Garrett, L T Diemel, David R TomlinsonAbstract:1 Neurogenic vasoactive responses in rat skin were investigated following 8 weeks of streptozotocin-induced diabetes to determine the effect of diabetes and of treatment with insulin and nerve growth factor (NGF) treatment. 2 Diabetic rats were divided into three groups: untreated; insulin (4 IU day−1 by s.c. implant weeks 4–8) treated; Nerve Growth Factor, NGF, (0.2 mg kg−1 three times weekly, weeks 4–8) treated. A fourth group served as a non-diabetic control. 3 Electrical stimulation of the saphenous nerve (10 V, 2 Hz, 1 ms for 30 s) increased blood flow in the ipsilateral paw skin, as measured by laser Doppler flowmetry. The peak increase was similar between groups, but the time taken for flow to return to a steady baseline was significantly (P<0.01) reduced in untreated diabetic rats, when compared with non-diabetic controls, but not significantly reduced in the insulin- or NGF-treated diabetic groups. 4 A second stimulation of the saphenous nerve (10 V, 2 Hz, 1 ms for 5 min) produced Plasma Extravasation, measured by the extravascular accumulation of 125l-albumin, in the skin. Plasma Extravasation was significantly attenuated (P<0.001) in the untreated diabetic group, but not the insulin-treated group, compared to non-diabetic controls. Plasma Extravasation was present, though reduced, in the NGF-treated group. 5 Plasma Extravasation induced by intradermal injections of substance P with and without CGRP was similar in all groups indicating no decrease in vascular responsiveness to exogenously applied neuropeptides. The results suggest that release of neuropeptides is diminished in diabetes and that treatment with either insulin or NGF can restore neurogenic microvascular vasoactive responses towards normal. British Journal of Pharmacology (1998) 124, 1573–1579; doi:10.1038/sj.bjp.0701986
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effect of peroxynitrite on Plasma Extravasation microvascular blood flow and nociception in the rat
British Journal of Pharmacology, 1997Co-Authors: Victoria Ridger, S A B Greenacre, R L C Handy, Barry Halliwell, P K Moore, Matthew Whiteman, Susan D BrainAbstract:1 Peroxynitrite (ONOO−) is a cytotoxic species, formed by the reaction between nitric oxide and superoxide free radicals, that may be involved in inflammation. In this study we have investigated the effect of peroxynitrite on Plasma Extravasation and microvascular blood flow in the dorsal skin and on nociceptive responses in the hind paw of the rat. 2 Male Wistar rats were anaesthetized and their dorsal skin shaved. Plasma Extravasation was measured by the extravascular accumulation of 125I-labelled albumin over 0–45 min and 0–240 min. Blood flow was measured by laser-Doppler flowmetry over 0–240 min. Studies in the hind paw were carried out in the conscious rat. Hind paw weight changes were determined by volume displacement and nociception by a mechanical hyperalgesia technique. 3 Intradermal (i.d.) peroxynitrite (100–200 nmol site−1) produced a significant (P<0.01) dose-dependent increase in Plasma Extravasation in dorsal skin over 0–45 min which was not increased over 45–240 min. Plasma Extravasation was significantly (P<0.001) decreased in rats pretreated with the anti-inflammatory steroid dexamethasone (1 mg kg−1, i.v.; −180 min), but not modulated by treatment with the hydrogen peroxide deactivator catalase (2200 u site−1), or the superoxide scavenger superoxide dismutase (500 u site−1), effective doses of the tachykinin NK1 antagonist SR140333 (1 nmol site−1), the cyclo-oxygenase inhibitor indomethacin (358 μmol site−1), or combined pretreatment with mepyramine (histamine H1-receptor antagonist; 2.8 nmol site−1) and methysergide (5-HT antagonist; 1.9 nmol site−1). 4 Microvascular blood flow was significantly (P<0.05) increased 30 and 120 min after i.d. peroxynitrite (100 nmol site−1) in dorsal skin and remained raised until the end of the recording period (240 min). The increase in blood flow was unaffected by dexamethasone (1 mg kg−1, i.v.; −180 min) or indomethacin (10 mg kg−1, s.c.; −30 min). 5 Hind paw volume was significantly (P<0.001) increased 30 min after intraplantar peroxynitrite (87.5 and 175 nmol paw−1) and remained raised for the duration of the experiment (360 min). By comparison, nociception was not altered by intraplantar peroxynitrite. 6 These data indicate that peroxynitrite can cause an increase in both Plasma Extravasation and blood flow, suggesting that peroxynitrite could be of biological relevance to microvascular responses. These findings may be of importance in the pathology of inflammatory diseases in which peroxynitrite formation occurs. British Journal of Pharmacology (1997) 122, 1083–1088; doi:10.1038/sj.bjp.0701498
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effect of the inducible nitric oxide synthase inhibitors aminoguanidine and l n6 1 iminoethyl lysine on zymosan induced Plasma Extravasation in rat skin
Journal of Immunology, 1997Co-Authors: Victoria Ridger, E R Pettipher, C E Bryant, Susan D BrainAbstract:The effect of nitric oxide synthase (NOS) inhibitors on Plasma Extravasation in a rat model of zymosan-induced inflammation has been investigated. Plasma Extravasation was determined in response to intradermal test agents over 0 to 45 min or 0 to 4 h by the accumulation of i.v. injected 125I-labeled human serum albumin. Zymosan (1-100 microg/site) produced a dose- and time-dependent Plasma Extravasation. N(G)-nitro-L-arginine methyl ester (30-300 nmol/site), but not aminoguanidine (AG; 10-300 nmol/site) or L-N6-(1-iminoethyl)lysine (L-NIL; 10-300 nmol/site), significantly (p < 0.01) inhibited zymosan-induced (10 microg/site) Plasma Extravasation over 0 to 45 min. However, both AG and L-NIL produced significant (p < 0.05) inhibition over 0 to 4 h. The inhibition produced by AG was reversed by i.v. L-arginine or by coinjection of the vasodilator, calcitonin gene-related peptide. Zymosan (10-100 microg/site) induced an increase in dermal blood flow (laser-Doppler flowmetry) and this was inhibited by AG. Neutrophils were depleted selectively with antiserum, but this did not affect Plasma Extravasation except at the highest dose of zymosan (100 microg/site). Furthermore, zymosan-induced edema was not modified at either time point by pretreatment with the cyclooxygenase inhibitor indomethacin (30 micromol/kg, s.c., -30 min). In conclusion, in this model of dermal inflammation, it is suggested that inducible NOS inhibitors selectively remove an inducible NOS component that, at least in part, acts to increase microvascular blood flow and thus the edema formation observed during 0 to 4 h. There is no evidence of a contributory role for neutrophils or cyclooxygenase products in this model.
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involvement of sensory neuropeptides in the development of Plasma Extravasation in rat dorsal skin following thermal injury
British Journal of Pharmacology, 1996Co-Authors: L Siney, Susan D BrainAbstract:Abstract 1. The involvement of the neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP) in Plasma Extravasation following thermal injury of rat dorsal skin was investigated. 2. Heat applied to the dorsal skin of anaesthetized rats by a temperature-controlled skin heater (1 cm diameter) for 5 min induced temperature-dependent Plasma protein Extravasation at 46 degrees C to 50 degrees C measured over the 20 min following initiation of heat. 3. The NK1-receptor antagonist, SR140333, at doses above 36 nmol kg-1, significantly (P < 0.05) inhibited Plasma Extravasation by up to 79 +/- 3% (120 nmol kg-1) after heat application at 48 degrees C and by up to 53 +/- 10% (120 nmol kg-1) after heat application at 50 degrees C. 4. The CGRP1-receptor antagonist, CGRP8-37, at doses of 200 and 400 nmol kg-1, significantly inhibited (P < 0.01) Plasma Extravasation by 55 +/- 9 and 60 +/- 12%, respectively, after heat application at 48 degrees C. At a dose of 200 nmol kg-1 CGRP8-37 inhibited Plasma Extravasation by 41 +/- 8% after heat application at 50 degrees C. 5. SR140333, 120 nmol kg-1, and CGRP8-37, 200 nmol kg-1 together significantly (P < 0.01) inhibited Plasma Extravasation by 84 +/- 15% after heating at 48 degrees C for 5 min. 6. In experiments where the response was measured for 0-5, 5-10, 10-15 or 15-20 min, SR140333, 120 nmol kg-1, significantly (P < 0.05) inhibited Plasma Extravasation which had accumulated during all the time periods measured. In comparison, CGRP8-37, 200 nmol kg-1, was significantly (P < 0.05) effective at time-points up to 15 min after initiation of injury. 7. In longer term experiments Plasma protein Extravasation continued for at least 95 min after initiation of thermal injury. SR140333, at a dose of 120 nmol kg-1, significantly inhibited Plasma Extravasation for up to 65 min after initiation of injury. 8. In conclusion, the data from the present study demonstrate that both SP and CGRP are likely to have a role in the acute Plasma Extravasation after thermal injury. In addition, evidence suggests SP may have a role in Plasma Extravasation for up to 65 min.
Jun Sakurai - One of the best experts on this subject based on the ideXlab platform.
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involvement of tumour necrosis factor alpha in clostridium perfringens beta toxin induced Plasma Extravasation in mice
British Journal of Pharmacology, 2008Co-Authors: Masahiro Nagahama, Atsushi Kihara, H Kintoh, Masataka Oda, Jun SakuraiAbstract:Background and purpose: Clostridium perfringens beta-toxin, an important agent of necrotic enteritis, causes Plasma Extravasation due to the release of a tachykinin NK1 receptor agonist in mouse skin. In this study, we investigated the role of cytokines in beta-toxin-induced Plasma Extravasation. Experimental approach: Male Balb/c, C3H/HeN and C3H/HeJ mice were anaesthetized with pentobarbitone and beta-toxin was injected i.d. into shaved dorsal skin. SR140333, capsaicin, chlorpromazine and pentoxifylline were given as pretreatment when required before the injection of the toxin. Cytokines in the dorsal skin were measured by ELISA. Key results: Injection (i.d.) of beta-toxin induced a dose-dependent increase in dermal TNF-α and interleukin (IL)-1β levels with a concomitant increase in Plasma Extravasation, but not the release of IL-6. SR140333 and capsaicin significantly inhibited the toxin-induced release of TNF-α and IL-1β. The Plasma Extravasation and the release of TNF-α induced by beta-toxin were significantly inhibited by chlorpromazine and pentoxifylline which inhibit the release of TNF-α. The toxin-induced Plasma Extravasation in mouse skin was attenuated by pretreatment with a monoclonal antibody against TNF-α, but not anti-IL-1β. Furthermore, the toxin caused an increase in Plasma Extravasation in both C3H/HeN (TLR4-intact) and C3H/HeJ (TLR4-deficient) mice. In C3H/HeN mice, the toxin-induced leakage was not inhibited by pretreatment with anti-TLR4/MD-2 antibody. Conclusions and implications: These observations show that beta-toxin-induced Plasma Extravasation in mouse skin is related to the release of TNF-α via the mechanism involving tachykinin NK1 receptors, but not via TLR4. British Journal of Pharmacology (2008) 153, 1296–1302; doi:10.1038/bjp.2008.9; published online 11 February 2008
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involvement of tachykinin receptors in clostridium perfringens beta toxin induced Plasma Extravasation
British Journal of Pharmacology, 2003Co-Authors: Masahiro Nagahama, Atsushi Kihara, Shinsuke Morimitsu, Masahiko Akita, Koujun Setsu, Jun SakuraiAbstract:Clostridium perfringens beta-toxin causes dermonecrosis and oedema in the dorsal skin of animals. In the present study, we investigated the mechanisms of oedema induced by the toxin. The toxin induced Plasma Extravasation in the dorsal skin of Balb/c mice. The Extravasation was significantly inhibited by diphenhydramine, a histamine 1 receptor antagonist. However, the toxin did not cause the release of histamine from mouse mastocytoma cells. Tachykinin NK1 receptor antagonists, [D-Pro2, D-Trp7,9]-SP, [D-Pro4, D-Trp7,9]-SP and spantide, inhibited the toxin-induced leakage in a dose-dependent manner. Furthermore, the non-peptide tachykinin NK1 receptor antagonist, SR140333, markedly inhibited the toxin-induced leakage. The leakage induced by the toxin was markedly reduced in capsaicin-pretreated mouse skin but the leakage was not affected by systemic pretreatment with a calcitonin gene-related peptide receptor antagonist (CGRP8-37). The toxin-induced leakage was significantly inhibited by the N-type Ca2+ channel blocker, ω-conotoxin MVIIA, and the bradykinin B2 receptor antagonist, HOE140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin), but was not affected by the selective L-type Ca2+ channel blocker, verapamil, the P-type Ca2+ channel blocker, ω-agatoxin IVA, tetrodotoxin (TTX), the TTX-resistant Na+ channel blocker, carbamazepine, or the sensory nerve conduction blocker, lignocaine. These results suggest that Plasma Extravasation induced by beta-toxin in mouse skin is mediated via a mechanism involving tachykinin NK1 receptors. British Journal of Pharmacology (2003) 138, 23–30. doi:10.1038/sj.bjp.0705022
Paul Green - One of the best experts on this subject based on the ideXlab platform.
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sexual dimorphism in the effect of nonhabituating stress on neurogenic Plasma Extravasation
European Journal of Neuroscience, 2005Co-Authors: Paul Green, Jon D. LevineAbstract:The sympathoadrenal axis contributes to the sexual dimorphism of the inflammatory response. As stress both activates the sympathoadrenal axis and profoundly affects inflammation and inflammatory disease, we evaluated whether stress exerts a sexually dimorphic effect on a major component of the inflammatory response, Plasma Extravasation. We evaluated the effect of a nonhabituating stress, repeated intermittent sound (30 min/day for 4 days), on neurogenic synovial Plasma Extravasation, induced by bradykinin in the rat knee joint. Sound stress profoundly inhibited bradykinin-induced Plasma Extravasation in male rats, but profoundly enhanced it in female rats. These effects took 24 h to fully develop after the last exposure to stress. In gonadectomized males, bradykinin-induced Plasma Extravasation was lower than intact males, and sound stress now enhanced it, i.e. gonadectomized males were phenotypically like intact females. In gonadectomized females, bradykinin-induced Plasma Extravasation was greater than in intact adult females, and sound stress still enhanced it. Adrenal enucleation significantly attenuated the effect of sound stress on bradykinin-induced Plasma Extravasation in both male and female rats. We tested the hypothesis that these effects of sound stress were due to sustained enhanced Plasma levels of stress hormones. Corticosterone and epinephrine, only when administered in combination, over five days, produced a qualitatively similar effect as sound stress, i.e. bradykinin-induced Plasma Extravasation was significantly decreased in males and increased in females. These findings suggest that a combined effect of the hypothalamic-pituitary adrenal and sympathoadrenal stress axes are responsible for the marked sexual dimorphism in the effect of stress on the inflammatory response.
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opioid inhibition of formalin induced changes in Plasma Extravasation and local blood flow in rats
Pain, 2000Co-Authors: Paul Green, Bradley K Taylor, Michael A Peterson, Robyn E Roderick, Janelle Tate, Jon O Levine, Allan I BasbaumAbstract:Hindpaw injection of dilute formalin produces brief (Phase 1) and persistent (Phase 2) nociceptive responses in the rat. We recently showed that systemically-administered remifentanil during Phase 1 interacted with peripheral opioid receptors to delay the onset and termination of Phase 2 (Taylor et al., 1997b). To test the hypothesis that opioid inhibition of proinflammatory events during Phase 1 contributed to this delay, we evaluated the effects of remifentanil on the time course of formalin-induced inflammation. We found that formalin increased paw thickness (edema), Plasma Extravasation and local blood flow within minutes of its injection, i.e. during Phase 1. Each of these responses was blocked during remifentanil administration (30 microg/kg i.v. bolus, followed 90 s later with a 15 microg/kg/min infusion for 13.5 min), indicating that opioids inhibit Phase 1 inflammation. Opioid blockade of the blood flow response could be reversed with a peripherally-acting opioid antagonist, naloxone methiodide, indicating that remifentanil acted upon peripheral opioid receptors. Although the administration of remifentanil during Phase 1 did not reduce the magnitude of inflammatory responses during Phase 2, it did delay the onset and termination of edema during Phase 2. As this corresponds to the effects of remifentanil on nociceptive responses during Phase 2, we suggest that opioid analgesics act upon peripheral sites to inhibit inflammation during Phase 1, leading to a delay in the temporal profile of inflammatory (and likely nociceptive) responses during Phase 2.
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inhibition of bradykinin induced Plasma Extravasation produced by noxious cutaneous and visceral stimuli and its modulation by vagal activity
Journal of Neurophysiology, 1997Co-Authors: Frederick Jia-pei Miao, W. Janig, Paul Green, Jon D. LevineAbstract:Miao, Frederick Jia-Pei, Wilfrid Janig, Paul G. Green, and Jon D. Levine. Inhibition of bradykinin-induced Plasma Extravasation produced by noxious cutaneous and visceral stimuli and its modulation...
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sympathetic dependence in bradykinin induced synovial Plasma Extravasation is dose related
Neuroscience Letters, 1996Co-Authors: Frederick Jia-pei Miao, W. Janig, Paul Green, Terence J Coderre, Jon D. LevineAbstract:Abstract While previous studies have implicated a role for sympathetic postganglionic neuron-terminals in bradykinin-induced Plasma Extravasation, a recent report by Cambridge and Brain [Br. J. Pharmacol., 115 (1995) 641–647] has suggested that it is sympathetic-independent. However, the doses of bradykinin used in these two groups of studies were considerably different. Therefore, in the present study, we characterized the sympathetic-dependence of Plasma Extravasation at varying doses of bradykinin. By measuring the concentration of Evans blue dye Extravasation into the joint perfusate following its intravenous injection, bradykinin-induced Plasma Extravasation in the knee joint cavity was determined spectrophotometrically. To examine the role of sympathetic postganglionic neuron terminals in mediating bradykinin-induced Plasma Extravasation, we used surgical ablation of the lumbar sympathetic chain. Intra-articular perfusion of BK dose-dependently increased synovial Plasma Extravasation. After surgical sympathectomy, the dose-response curve for bradykinin-induced Plasma Extravasation was significantly shifted to the right. We conclude that at concentrations observed in inflamed tissues (between 10−8 and 10−7 M), bradykinin-induced Plasma Extravasation is largely mediated by sympathetic postganglionic neuron terminals.
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5 hydroxytryptamine induced synovial Plasma Extravasation is mediated via 5 hydroxytryptamine2a receptors on sympathetic efferent terminals
Journal of Pharmacology and Experimental Therapeutics, 1995Co-Authors: P A Pierce, Paul Green, Guoxi Xie, S J Peroutka, J D LevineAbstract:5-Hydroxytryptamine (5-HT) is known to act in peripheral tissues to produce pain and inflammation, yet the mechanisms underlying 5-HT-induced inflammation have not been well studied. The present study uses a rat knee joint model of inflammation (synovial Plasma Extravasation) and molecular biological techniques to determine the site of action of 5-HT and the specific 5-HT receptor subtype mediating synovial 5-HT-induced Plasma Extravasation. 5-HT (1 microM) stimulates synovial Plasma Extravasation 7-fold above base-line levels. Surgical lumbar sympathectomy, but not C-fiber depletion by neonatal capsaicin, dramatically reduces 5-HT-induced synovial Plasma Extravasation (P < .001), indicating that sympathetic efferents mediate this effect. Polymerase chain reaction amplification of 5-HT receptor cDNA demonstrates that 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A and 5-HT3, but not the 5-HT2C, receptor subtypes are present in lumbar sympathetic ganglia. With selective ligands for these receptor subtypes, we demonstrate that 5-HT-induced synovial Plasma Extravasation is mediated via the 5-HT2A receptor. These findings suggest a role for 5-HT2A antagonists in various synovial inflammatory pain states.
Masahiro Nagahama - One of the best experts on this subject based on the ideXlab platform.
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involvement of tumour necrosis factor alpha in clostridium perfringens beta toxin induced Plasma Extravasation in mice
British Journal of Pharmacology, 2008Co-Authors: Masahiro Nagahama, Atsushi Kihara, H Kintoh, Masataka Oda, Jun SakuraiAbstract:Background and purpose: Clostridium perfringens beta-toxin, an important agent of necrotic enteritis, causes Plasma Extravasation due to the release of a tachykinin NK1 receptor agonist in mouse skin. In this study, we investigated the role of cytokines in beta-toxin-induced Plasma Extravasation. Experimental approach: Male Balb/c, C3H/HeN and C3H/HeJ mice were anaesthetized with pentobarbitone and beta-toxin was injected i.d. into shaved dorsal skin. SR140333, capsaicin, chlorpromazine and pentoxifylline were given as pretreatment when required before the injection of the toxin. Cytokines in the dorsal skin were measured by ELISA. Key results: Injection (i.d.) of beta-toxin induced a dose-dependent increase in dermal TNF-α and interleukin (IL)-1β levels with a concomitant increase in Plasma Extravasation, but not the release of IL-6. SR140333 and capsaicin significantly inhibited the toxin-induced release of TNF-α and IL-1β. The Plasma Extravasation and the release of TNF-α induced by beta-toxin were significantly inhibited by chlorpromazine and pentoxifylline which inhibit the release of TNF-α. The toxin-induced Plasma Extravasation in mouse skin was attenuated by pretreatment with a monoclonal antibody against TNF-α, but not anti-IL-1β. Furthermore, the toxin caused an increase in Plasma Extravasation in both C3H/HeN (TLR4-intact) and C3H/HeJ (TLR4-deficient) mice. In C3H/HeN mice, the toxin-induced leakage was not inhibited by pretreatment with anti-TLR4/MD-2 antibody. Conclusions and implications: These observations show that beta-toxin-induced Plasma Extravasation in mouse skin is related to the release of TNF-α via the mechanism involving tachykinin NK1 receptors, but not via TLR4. British Journal of Pharmacology (2008) 153, 1296–1302; doi:10.1038/bjp.2008.9; published online 11 February 2008
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involvement of tachykinin receptors in clostridium perfringens beta toxin induced Plasma Extravasation
British Journal of Pharmacology, 2003Co-Authors: Masahiro Nagahama, Atsushi Kihara, Shinsuke Morimitsu, Masahiko Akita, Koujun Setsu, Jun SakuraiAbstract:Clostridium perfringens beta-toxin causes dermonecrosis and oedema in the dorsal skin of animals. In the present study, we investigated the mechanisms of oedema induced by the toxin. The toxin induced Plasma Extravasation in the dorsal skin of Balb/c mice. The Extravasation was significantly inhibited by diphenhydramine, a histamine 1 receptor antagonist. However, the toxin did not cause the release of histamine from mouse mastocytoma cells. Tachykinin NK1 receptor antagonists, [D-Pro2, D-Trp7,9]-SP, [D-Pro4, D-Trp7,9]-SP and spantide, inhibited the toxin-induced leakage in a dose-dependent manner. Furthermore, the non-peptide tachykinin NK1 receptor antagonist, SR140333, markedly inhibited the toxin-induced leakage. The leakage induced by the toxin was markedly reduced in capsaicin-pretreated mouse skin but the leakage was not affected by systemic pretreatment with a calcitonin gene-related peptide receptor antagonist (CGRP8-37). The toxin-induced leakage was significantly inhibited by the N-type Ca2+ channel blocker, ω-conotoxin MVIIA, and the bradykinin B2 receptor antagonist, HOE140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin), but was not affected by the selective L-type Ca2+ channel blocker, verapamil, the P-type Ca2+ channel blocker, ω-agatoxin IVA, tetrodotoxin (TTX), the TTX-resistant Na+ channel blocker, carbamazepine, or the sensory nerve conduction blocker, lignocaine. These results suggest that Plasma Extravasation induced by beta-toxin in mouse skin is mediated via a mechanism involving tachykinin NK1 receptors. British Journal of Pharmacology (2003) 138, 23–30. doi:10.1038/sj.bjp.0705022