In vivo stimulation of 12(S)-lipoxygenase in the rat skin by bradykinin and platelet activating factor: formation of 12(S)-HETE and hepoxilins, and actions on vascular permeability

Wang, Mei Mei; Reynaud, Dénis; Pace-Asciak, Cecil R.

doi:10.1016/s0005-2760(98)00128-3

Cited by 29 publications

(15 citation statements)

References 40 publications

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“…II, C3A and D6B). In accord, a bradykinin-stimulated production of 12-HETE in rat DRG neurons and skin was demonstrated (653,761).…”

Section: Role Of Endogenous Lipoxygenase Products In Inflammatory mentioning

confidence: 78%

“…Indirect support for this hypothesis was soon provided by a study pharmacologically showing that bradykinin effects on cultured rat DRG neurons and cutaneous nerve fibers could be antagonized by capsazepine, the competitive blocker of the ligand-binding site of TRPV1, and by LOX inhibitors, although in behavioral experiments the LOX antagonist baicalein by itself, in absence of bradykinin, prolonged the noxious heat withdrawal latency (653). Nonetheless, bradykinin stimulated via the 12-LOX pathway the production of 12-HETE in sensory neurons in vitro and in rat skin in vivo (653,710,761). Furthermore, 12-LOX is exclusively expressed in platelets, and activated platelets excite nociceptors and induce hyperalgesia (606,641).…”

Section: Trp Channels In Bradykinin Receptor Signalingmentioning

confidence: 99%

“…In acutely isolated cardiac DRG neurons, the bradykinin-induced increase in firing rate and decrease of the threshold for action potential generation were inhibited by a selective 12-LOX inhibitor (781). One may remember that bradykinin stimulated via the 12-LOX pathway the production of 12-HETE, a TRPV1 agonist, in sensory neurons in vitro and in rat skin in vivo (653,761). The overt nociception evoked by intraplantar injection of bradykinin in mice was reduced by inhibitors of either PLA 2 or 5-LOX (186).…”

Section: B) Contribution Of Prostanoids Lipoxygenase Products and Nmentioning

confidence: 99%

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Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Pethő

Reeh

2012

Physiological Reviews

234

200

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Peripheral mediators can contribute to the development and maintenance of inflammatory and neuropathic pain and its concomitants (hyperalgesia and allodynia) via two mechanisms. Activation or excitation by these substances of nociceptive nerve endings or fibers implicates generation of action potentials which then travel to the central nervous system and may induce pain sensation. Sensitization of nociceptors refers to their increased responsiveness to either thermal, mechanical, or chemical stimuli that may be translated to corresponding hyperalgesias. This review aims to give an account of the excitatory and sensitizing actions of inflammatory mediators including bradykinin, prostaglandins, thromboxanes, leukotrienes, platelet-activating factor, and nitric oxide on nociceptive primary afferent neurons. Manifestations, receptor molecules, and intracellular signaling mechanisms of the effects of these mediators are discussed in detail. With regard to signaling, most data reported have been obtained from transfected nonneuronal cells and somata of cultured sensory neurons as these structures are more accessible to direct study of sensory and signal transduction. The peripheral processes of sensory neurons, where painful stimuli actually affect the nociceptors in vivo, show marked differences with respect to biophysics, ultrastructure, and equipment with receptors and ion channels compared with cellular models. Therefore, an effort was made to highlight signaling mechanisms for which supporting data from molecular, cellular, and behavioral models are consistent with findings that reflect properties of peripheral nociceptive nerve endings. Identified molecular elements of these signaling pathways may serve as validated targets for development of novel types of analgesic drugs.

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“…II, C3A and D6B). In accord, a bradykinin-stimulated production of 12-HETE in rat DRG neurons and skin was demonstrated (653,761).…”

Section: Role Of Endogenous Lipoxygenase Products In Inflammatory mentioning

confidence: 78%

Section: Trp Channels In Bradykinin Receptor Signalingmentioning

confidence: 99%

Section: B) Contribution Of Prostanoids Lipoxygenase Products and Nmentioning

confidence: 99%

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Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Pethő

Reeh

2012

Physiological Reviews

234

200

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“…The excitation of cultured sensory neurons or sensory nerve fibers of the adult rat skin by BK is greatly restricted by inhibitors of PLA 2 -LOX -TRPV1 pathway (McGuirk & Dolphin, 1992;Shin et al, 2002). In fact, BK stimulates LOX product formation by sensory neurones in vitro and by skin in vivo (Gammon et al, 1989;Shin et al, 2002;Wang et al, 1999). It has also been reported that BK-induced thermal hyperalgesia is blocked by LOX inhibition (Shin et al, 2002).…”

Section: J Ferreira Et Almentioning

confidence: 99%

Contribution of vanilloid receptors to the overt nociception induced by B₂ kinin receptor activation in mice

Ferreira

Silva

Calixto

2004

British J Pharmacology

168

101

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1 The vanilloid receptor (TRPV1) is viewed as a molecular integrator of several nociceptive stimuli. In the present study, we have investigated the role played by TRPV1 in the nociceptive response induced by the peripheral activation of kinin B 2 receptor in mice. 2 The intraplantar (i.pl.) administration of bradykinin (BK) and the selective B 2 agonist Tyr 8 -BK, or the vanilloid agonists resiniferatoxin and capsaicin, into the mouse paw induced a dose-related overt nociception of short duration. The B 2 receptor antagonist Hoe 140 inhibited BK-induced, but not capsaicin-induced, nociceptive response. On the other hand, the TRPV1 antagonist capsazepine inhibited both capsaicin-and BK-mediated nociception. 3 Repeated injections of BK or capsaicin produced desensitization to their nociceptive response. Capsaicin desensitization greatly reduced BK-induced nociception, but in contrast, the desensitization to BK increased the capsaicin response. 4 Administration of low doses of capsaicin or acidified saline did not produce nociception when administered alone, but caused a pronounced effect when administered in association with a subthreshold dose of BK. Moreover, the degeneration of the subset of primary afferent fibers, sensitive to capsaicin, abolished both capsaicin-and BK-induced nociception. 5 The inhibition of phospholipase C (PLC), protein kinase C or phospholipase A 2 markedly decreased the nociception caused by BK, but not that of capsaicin. BK administration increased leukotriene B 4 levels in the injected paw. Likewise, BK-induced overt nociception was decreased by lipoxygenase (LOX) inhibition. 6 These results demonstrate that BK produces overt nociception mediated by TRPV1 receptor stimulation, via PLC pathway activation and LOX product formation.

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“…Given that linoleic acid is used in vivo for biosynthesis of AA and that HNE is generated by peroxidation of 12/15-LOX products of n-6 PUFA, we hypothesized that spinal 12-LOX metabolites of AA, particularly hepoxilins, also contribute to inflammatory hyperalgesia through stimulation of nociceptive afferents. Although hepoxilins increase intracellular Ca 2+ in neutrophils (19,20) and neurons (21) and enhance vascular permeability in rat skin (22,23), its receptors remain undefined. Our findings demonstrate that peripheral inflammation increases spinal HXA 3 , which produces hyperesthesia via activation of TRPV1 and TRPA1 and spinal SP release.…”

mentioning

confidence: 99%

Spinal 12-lipoxygenase-derived hepoxilin A₃contributes to inflammatory hyperalgesia via activation of TRPV1 and TRPA1 receptors

Gregus¹,

Doolen

Dumlao

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

105

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Peripheral inflammation initiates changes in spinal nociceptive processing leading to hyperalgesia. Previously, we demonstrated that among 102 lipid species detected by LC-MS/MS analysis in rat spinal cord, the most notable increases that occur after intraplantar carrageenan are metabolites of 12-lipoxygenases (12-LOX), particularly hepoxilins (HXA 3 and HXB 3 ). Thus, we examined involvement of spinal LOX enzymes in inflammatory hyperalgesia. In the current work, we found that intrathecal (IT) delivery of the LOX inhibitor nordihydroguaiaretic acid prevented the carrageenan-evoked increase in spinal HXB 3 at doses that attenuated the associated hyperalgesia. Furthermore, IT delivery of inhibitors targeting 12-LOX (CDC, Baicalein), but not 5-LOX (Zileuton) dosedependently attenuated tactile allodynia. Similarly, IT delivery of 12-LOX metabolites of arachidonic acid 12(S)-HpETE, 12(S)-HETE, HXA 3 , or HXB 3 evoked profound, persistent tactile allodynia, but 12(S)-HpETE and HXA 3 produced relatively modest, transient heat hyperalgesia. The pronociceptive effect of HXA 3 correlated with enhanced release of Substance P from primary sensory afferents. Importantly, HXA 3 triggered sustained mobilization of calcium in cells stably overexpressing TRPV1 or TRPA1 receptors and in acutely dissociated rodent sensory neurons. Constitutive deletion or antagonists of TRPV1 (AMG9810) or TRPA1 (HC030031) attenuated this action. Furthermore, pretreatment with antihyperalgesic doses of AMG9810 or HC030031 reduced spinal HXA 3 -evoked allodynia. These data indicate that spinal HXA 3 is increased by peripheral inflammation and promotes initiation of facilitated nociceptive processing through direct activation of TRPV1 and TRPA1 at central terminals.eicosanoid | pain | central sensitization T issue injury and inflammation are associated with hyperalgesia mediated by facilitated spinal nociceptive processing that can be modulated by lipids derived from arachidonic acid (AA) and other polyunsaturated fatty acids (PUFA), including eicosanoids synthesized via three enzymatic pathways: (i) cyclooxygenase (COX)-prostaglandins (PG); (ii) 5-, 12-, and 12/15-lipoxygenases (LOX)-leukotrienes, hydroxyeicosatetraenoic acids (HETEs), hepoxilins (HXA 3 and HXB 3 ), lipoxins, resolvins, and protectins; and (iii) cytochrome P450-epoxyeicosatrienoic acids and HETEs (1). Substantial evidence indicates that peripheral injury or direct activation of spinal dorsal horn receptors [Neurokinin 1 (NK1), AMPA, and NMDA] increases eicosanoid formation and that spinal delivery of COX inhibitors reduces the associated hyperalgesia (2, 3). Recently, we reported that paw carrageenan increases spinal production of both COX and 12-LOX metabolites of AA, including 12(S)-HETE in cerebrospinal fluid (CSF) and hepoxilins in the lumbar spinal cord (4).Several groups point to a peripheral role for 5-and 12-LOX in nociception, as shown by antihyperalgesic actions of LOX inhibitors administered via systemic routes (5-9). It has been suggested that spinal 12-LOX may play a r...

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In vivo stimulation of 12(S)-lipoxygenase in the rat skin by bradykinin and platelet activating factor: formation of 12(S)-HETE and hepoxilins, and actions on vascular permeability

Cited by 29 publications

References 40 publications

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Contribution of vanilloid receptors to the overt nociception induced by B₂ kinin receptor activation in mice

Spinal 12-lipoxygenase-derived hepoxilin A₃contributes to inflammatory hyperalgesia via activation of TRPV1 and TRPA1 receptors

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In vivo stimulation of 12(S)-lipoxygenase in the rat skin by bradykinin and platelet activating factor: formation of 12(S)-HETE and hepoxilins, and actions on vascular permeability

Cited by 29 publications

References 40 publications

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

Contribution of vanilloid receptors to the overt nociception induced by B2 kinin receptor activation in mice

Spinal 12-lipoxygenase-derived hepoxilin A3contributes to inflammatory hyperalgesia via activation of TRPV1 and TRPA1 receptors

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Contribution of vanilloid receptors to the overt nociception induced by B₂ kinin receptor activation in mice

Spinal 12-lipoxygenase-derived hepoxilin A₃contributes to inflammatory hyperalgesia via activation of TRPV1 and TRPA1 receptors