The Role of TRPV1 in Different Subtypes of Dorsal Root Ganglion Neurons in Rat Chronic Inflammatory Nociception Induced by Complete Freund's Adjuvant

Yu, Long-Chuan; Yang, Fei; Luo, Hao; Liu, Fengyu; Han, Ji-Sheng; Xing, Guo-Gang; Wan, You

doi:10.1186/1744-8069-4-61

Cited by 162 publications

(136 citation statements)

References 27 publications

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“…S7 A and B). These observations corroborate other studies that use the same doses of these antagonists in different rodent models of inflammatory pain (14,29,30). Similarly, IT HXA 3 -induced tactile allodynia is significantly attenuated by spinal pretreatment with antihyperalgesic doses of HC030031 or AMG9810 (Fig.…”

Section: Hxa 3 Activates Trpv1 and Trpa1 On Sensory Neurons And Triggerssupporting

confidence: 90%

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.

106

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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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Section: Hxa 3 Activates Trpv1 and Trpa1 On Sensory Neurons And Triggerssupporting

confidence: 90%

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.

106

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“…DomBourian et al (2006) showed that there was an upregulation of TRPV1 in the DH of rats after spinal cord injury, and Tohda et al (2001) demonstrated that carrageenan-induced inflammation resulted in an increased transport of TRPV1 mRNA to neuron terminals in the DH. Both models were associated with thermal hyperalgesia, which has been shown to be blocked by intrathecal administration of TRPV1 antagonists such as 3,6-dihydro-3Ј- (Wang and Woolf, 2005;Cui et al, 2006;Yu et al, 2008). Studies have also shown that spinal TRPV1 is likely to be involved in the development of mechanical hyperalgesia (Kanai et al, 2007).…”

Section: E In the Spinal Cordmentioning

confidence: 99%

Unravelling the Mystery of Capsaicin: A Tool to Understand and Treat Pain

O’Neill

Brock²,

Olesen³

et al. 2012

Pharmacol Rev

292

244

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“…The rats were briefly anesthetized with 3% isoflurane, flexed over a tube, and a 27-gauge needle was inserted between the L5 and S1 vertebrae with a deflection of the tail indicating entry to the subarachnoid space. The dose of both agents were chosen based on previously published studies (Yu et al, 2008;Li et al, 2014b). AMG9810 was tested on both preestablished paclitaxel CIPN and as a preventative agent during chemotherapy.…”

Section: Methodsmentioning

confidence: 99%

The Cancer Chemotherapeutic Paclitaxel Increases Human and Rodent Sensory Neuron Responses to TRPV1 by Activation of TLR4

Li¹,

Adámek

Zhang³

et al. 2015

J. Neurosci.

203

234

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Peripheral neuropathy is dose limiting in paclitaxel cancer chemotherapy and can result in both acute pain during treatment and chronic persistent pain in cancer survivors. The hypothesis tested was that paclitaxel produces these adverse effects at least in part by sensitizing transient receptor potential vanilloid subtype 1 (TRPV1) through Toll-like receptor 4 (TLR4) signaling. The data show that paclitaxelinduced behavioral hypersensitivity is prevented and reversed by spinal administration of a TRPV1 antagonist. The number of TRPV1 ϩ neurons is increased in the dorsal root ganglia (DRG) in paclitaxel-treated rats and is colocalized with TLR4 in rat and human DRG neurons. Cotreatment of rats with lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides (LPS-RS), a TLR4 inhibitor, prevents the increase in numbers of TRPV1 ϩ neurons by paclitaxel treatment. Perfusion of paclitaxel or the archetypal TLR4 agonist LPS activated both rat DRG and spinal neurons directly and produced acute sensitization of TRPV1 in both groups of cells via a TLR4-mediated mechanism. Paclitaxel and LPS sensitize TRPV1 in HEK293 cells stably expressing human TLR4 and transiently expressing human TRPV1. These physiological effects also are prevented by LPS-RS. Finally, paclitaxel activates and sensitizes TRPV1 responses directly in dissociated human DRG neurons. In summary, TLR4 was activated by paclitaxel and led to sensitization of TRPV1. This mechanism could contribute to paclitaxel-induced acute pain and chronic painful neuropathy.

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The Role of TRPV1 in Different Subtypes of Dorsal Root Ganglion Neurons in Rat Chronic Inflammatory Nociception Induced by Complete Freund's Adjuvant

Cited by 162 publications

References 27 publications

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

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

Unravelling the Mystery of Capsaicin: A Tool to Understand and Treat Pain

The Cancer Chemotherapeutic Paclitaxel Increases Human and Rodent Sensory Neuron Responses to TRPV1 by Activation of TLR4

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The Role of TRPV1 in Different Subtypes of Dorsal Root Ganglion Neurons in Rat Chronic Inflammatory Nociception Induced by Complete Freund's Adjuvant

Cited by 162 publications

References 27 publications

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

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

Unravelling the Mystery of Capsaicin: A Tool to Understand and Treat Pain

The Cancer Chemotherapeutic Paclitaxel Increases Human and Rodent Sensory Neuron Responses to TRPV1 by Activation of TLR4

Contact Info

Product

Resources

About

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

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