Suppression of the p75 Neurotrophin Receptor in Uninjured Sensory Neurons Reduces Neuropathic Pain after Nerve Injury

Obata, Koichi; Katsura, Hirokazu; Sakùrai, Jun; Kobayashi, Kimiko; Yamanaka, Hiroki; Dai, Yi; Fukuoka, Tetsuo; Noguchi, Koichi

doi:10.1523/jneurosci.3188-06.2006

Cited by 75 publications

(57 citation statements)

References 77 publications

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“…TRPV1 up-regulation in undamaged primary sensory neurons has been implicated in nerve injuryinduced heat hyperalgesia (Ji et al 2002;Obata et al 2006). In the present study, AS knockdown of TLR3 expression did not attenuate nerve injury-induced heat hyperalgesia.…”

Section: R E T R a C T E Dcontrasting

confidence: 52%

THIS ARTICLE HAS BEEN RETRACTED: Toll‐like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury

Obata

Katsura

Miyoshi

et al. 2008

Journal of Neurochemistry

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Toll-like receptors (TLRs) play an essential role in innate immune responses and in the initiation of adaptive immune responses. Microglia, the resident innate immune cells in the CNS, express TLRs. In this study, we show that TLR3 is crucial for spinal cord glial activation and tactile allodynia after peripheral nerve injury. Intrathecal administration of TLR3 antisense oligodeoxynucleotide suppressed nerve injury-induced tactile allodynia, and decreased the phosphorylation of p38 mitogen-activated protein kinase, but not extracellular signal-regulated protein kinases 1/2, in spinal glial cells. Antisense knockdown of TLR3 also attenuated the activation of spinal microglia, but not astrocytes, caused by nerve injury. Furthermore, down-regulation of TLR3 inhibited nerve injuryinduced up-regulation of spinal pro-inflammatory cytokines, such as interleukin-1b, interleukin-6, and tumor necrosis factor-a. Conversely, intrathecal injection of the TLR3 agonist polyinosine-polycytidylic acid induced behavioral, morphological, and biochemical changes similar to those observed after nerve injury. Indeed, TLR3-deficient mice did not develop tactile allodynia after nerve injury or polyinosine-polycytidylic acid injection. Our results indicate that TLR3 has a substantial role in the activation of spinal glial cells and the development of tactile allodynia after nerve injury. Thus, blocking TLR3 in the spinal glial cells might provide a fruitful strategy for treating neuropathic pain.

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Section: R E T R a C T E Dcontrasting

confidence: 52%

THIS ARTICLE HAS BEEN RETRACTED: Toll‐like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury

Obata

Katsura

Miyoshi

et al. 2008

Journal of Neurochemistry

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“…Therefore, the most promising studies using growth factors have combined them with genetic intervention to up-regulate growth factor receptors or down-regulate their intrinsic inhibitors (Hollis et al, 2009;Sun et al, 2011). The second issue is that of undesirable side effects, especially that of neuropathic pain caused by neurotrophin administration (Obata et al, 2006;Jankowski and Koerber, 2009). Development of "painless" neurotrophins (Capsoni et al, 2011) may improve the usefulness of this family of growth factors in the context of regeneration.…”

Section: Kab-raf Expression and Pten Deletion Synergize To Increase Amentioning

confidence: 99%

B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS

O’Donovan¹,

Ma²,

Guo³

et al. 2014

J Cell Biol

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Activation of intrinsic growth programs that promote developmental axon growth may also facilitate axon regeneration in injured adult neurons. Here, we demonstrate that conditional activation of B-RAF kinase alone in mouse embryonic neurons is sufficient to drive the growth of long-range peripheral sensory axon projections in vivo in the absence of upstream neurotrophin signaling. We further show that activated B-RAF signaling enables robust regenerative growth of sensory axons into the spinal cord after a dorsal root crush as well as substantial axon regrowth in the crush-lesioned optic nerve. Finally, the combination of B-RAF gain-of-function and PTEN loss-of-function promotes optic nerve axon extension beyond what would be predicted for a simple additive effect. We conclude that cell-intrinsic RAF signaling is a crucial pathway promoting developmental and regenerative axon growth in the peripheral and central nervous systems.

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“…Upon redox modulation of the environment, and consequent PDI inactivation, ADAM17 adopts an active conformation which is accompanied by changes in disulfide bonds in the ADAM17 ectodomain (Willems et al, 2010). Consequently, activated ADAM17 processes pro-tumor necrosis factor ␣ and cleaves diverse cell-surface receptors and adhesion molecules, including the p75 neurotrophin receptor (Weskamp et al, 2004), which is involved in the development of nociceptive hypersensitivity (Obata et al, 2006). …”

Section: H Ubiquitin-mediated Proteasomal Protein Degradation and Prmentioning

confidence: 99%

SNO-ing at the Nociceptive Synapse?

et al. 2011

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Suppression of the p75 Neurotrophin Receptor in Uninjured Sensory Neurons Reduces Neuropathic Pain after Nerve Injury

Cited by 75 publications

References 77 publications

THIS ARTICLE HAS BEEN RETRACTED: Toll‐like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury

THIS ARTICLE HAS BEEN RETRACTED: Toll‐like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury

B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS

SNO-ing at the Nociceptive Synapse?

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