Injured nerve-derived COX2/PGE2 contributes to the maintenance of neuropathic pain in aged rats

Ma, Weiya; Chabot, Jean‐Guy; Vercauteren, F.; Quirion, Rémi

doi:10.1016/j.neurobiolaging.2008.08.002

Cited by 58 publications

(57 citation statements)

References 34 publications

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“…Perineural injection of a nonselective COX inhibitor reversed tactile allodynia and suppressed upregulation of EP 1 and EP 4 receptors in macrophages. Eighteen months after partial sciatic nerve ligation, tactile allodynia and thermal hyperalgesia were still observed (450). At this advanced age, COX-2 and PGE 2 upregulation were still observed in injured nerve, mainly in invading macrophages, together with an increased expression in the ipsilateral DRG of EP 1 and EP 4 (but not EP 2 and EP 3 ) receptors as well as TRPV1 channels.…”

Section: H Role Of Endogenous Prostanoids In Peripheral Mechanisms Omentioning

confidence: 96%

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

Pethő

Reeh

2012

Physiological Reviews

241

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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Section: H Role Of Endogenous Prostanoids In Peripheral Mechanisms Omentioning

confidence: 96%

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

Pethő

Reeh

2012

Physiological Reviews

241

200

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“…[44][45][46][47][48] Most interestingly, increased expression of EP 1 receptors has been reported in human injured brachial plexus nerves, painful neuromas and avulsion injured dorsal root ganglion (DRG).…”

Section: Is Pge 2 Involved In Neuropathic Pain?mentioning

confidence: 99%

Prostaglandin E2 and Pain-An Update

Kawabata

2011

Biological & Pharmaceutical Bulletin

275

189

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Prostaglandin E 2 (PGE 2 ), a cyclooxygenase (COX) product, is the best known lipid mediator that contributes to inflammatory pain. Nonsteroidal anti-inflammatory drugs (NSAIDs), inhibitors of COX-1 and/or COX-2, suppress inflammatory pain by reducing generation of prostanoids, mainly PGE 2 , while they exhibit gastrointestinal, renal and cardiovascular toxicities. Selective inhibitors of microsomal PGE synthase-1 and subtypeselective antagonists of PGE 2 receptors, particularly EP 1 and EP 4 , may be useful as analgesics with minimized side-effects. Protein kinase C (PKC) and PKA downstream of EP 1 and EP 4 , respectively, sensitize/activate multiple molecules including transient receptor potential vanilloid-1 (TRPV1) channels, purinergic P2X3 receptors, and voltage-gated calcium or sodium channels in nociceptors, leading to hyperalgesia. PGE 2 is also implicated in neuropathic and visceral pain and in migraine. Thus, PGE 2 has a great impact on pain signals, and pharmacological intervention in upstream and downstream signals of PGE 2 may serve as novel therapeutic strategies for the treatment of intractable pain.

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“…Even short-term hyperglycemia can produce oxidative damage and apoptosis in DRG neurons [17] . Inflammatory factors play an important role in DRG neuronal damage, especially in painful neuropathy [9,18,19] . In previous studies, lower glucose concentrations induced DRG neuron death in culture, whereas total glucose levels above 35 mmol/L produced hyperglycemic insult leading to DRG neuron death [20] .…”

Section: Introductionmentioning

confidence: 99%

Quercetin protects rat dorsal root ganglion neurons against high glucose-induced injury in vitro through Nrf-2/HO-1 activation and NF-κB inhibition

et al. 2013

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Aim: To examine the effects of quercetin, a natural antioxidant, on high glucose (HG)-induced apoptosis of cultured dorsal root ganglion (DRG) neurons of rats. Methods: DRG neurons exposed to HG (45 mmol/L) for 24 h were employed as an in vitro model of diabetic neuropathy. Cell viability, reactive oxygen species (ROS) level and apoptosis were determined. The expression of NF-кB, IкBα, phosphorylated IкBα and Nrf2 was examined using RT PCR and Western blot assay. The expression of hemeoxygenase-1 (HO-1), IL-6, TNF-α, iNOS, COX-2, and caspase-3 were also examined. Results: HG treatment markedly increased DRG neuron apoptosis via increasing intracellular ROS level and activating the NF-κB signaling pathway. Co-treatment with quercetin (2.5, 5, and 10 mmol/L) dose-dependently decreased HG-induced caspase-3 activation and apoptosis. Quercetin could directly scavenge ROS and significantly increased the expression of Nrf-2 and HO-1 in DRG neurons. Quercetin also dose-dependently inhibited the NF-κB signaling pathway and suppressed the expression of iNOS, COX-2, and proinflammatory cytokines IL-6 and TNF-α. Conclusion: Quercetin protects rat DRG neurons against HG-induced injury in vitro through Nrf-2/HO-1 activation and NF-κB inhibition, thus may be beneficial for the treatment of diabetic neuropathy.

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Injured nerve-derived COX2/PGE2 contributes to the maintenance of neuropathic pain in aged rats

Cited by 58 publications

References 34 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

Prostaglandin E2 and Pain-An Update

Quercetin protects rat dorsal root ganglion neurons against high glucose-induced injury in vitro through Nrf-2/HO-1 activation and NF-κB inhibition

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