NGF and GDNF differentially regulate TRPV1 expression that contributes to development of inflammatory thermal hyperalgesia

Amaya, Fumimasa; Shimosato, Goshun; Nagano, Masatoshi; Ueda, Masashi; Hashimoto, Satoru; Tanaka, Yoshifumi; Suzuki, Hidenori; Tanaka, Masaki

doi:10.1111/j.1460-9568.2004.03701.x

Cited by 216 publications

(150 citation statements)

References 47 publications

Supporting

Mentioning

140

Contrasting

Order By: Relevance

“…In addition, NGF, which has been shown to activate peripheral nociceptors, to affect gene expression at the cell body by retrograde signaling (Donnerer et al, 1992), and to be upregulated in peripheral tissue and DRG after inflammation and tissue injury (Woolf et al, 1994;Shu and Mendell, 1999;Amaya et al, 2004), can induce the upregulation of TRPV1 receptor expression and increase transport of TRPV1 to the peripheral nociceptor terminals (Ji et al, 2002). These studies support that the blockade of TRPV1 receptors in both the periphery and the CNS plays a role in chronic inflammatory pain.…”

Section: Discussionsupporting

confidence: 56%

TRPV1 Receptors in the CNS Play a Key Role in Broad-Spectrum Analgesia of TRPV1 Antagonists

Cui

Honoré²,

Zhong³

et al. 2006

J. Neurosci.

288

198

View full text Add to dashboard Cite

Vanilloid receptor type 1 (TRPV1) is a ligand-gated nonselective cation channel that is considered to be an important integrator of various pain stimuli such as endogenous lipids, capsaicin, heat, and low pH. In addition to expression in primary afferents, TRPV1 is also expressed in the CNS. To test the hypothesis that the CNS plays a differential role in the effect of TRPV1 antagonists in various types of pain, the analgesic effects of two TRPV1 antagonists with similar in vitro potency but different CNS penetration were compared in vivo. In these models, the potency of the two compounds was similar after intrathecal administration. However, when administered orally, A-784168, with good CNS penetration, was much more potent than A-795614. Together, these results demonstrate that TRPV1 receptors in the CNS play an important role in pain mediated by central sensitization. In addition, these results demonstrate that significant CNS penetration is necessary for a TRPV1 antagonist to produce broad-spectrum analgesia.

show abstract

Section: Discussionsupporting

confidence: 56%

TRPV1 Receptors in the CNS Play a Key Role in Broad-Spectrum Analgesia of TRPV1 Antagonists

Cui

Honoré²,

Zhong³

et al. 2006

J. Neurosci.

288

198

View full text Add to dashboard Cite

show abstract

“…In addition, CFAinduced inflammation induces the expression of the heat receptor TRPV1 within 1 day after application. Protein levels are increased as shown by Western blot and IHC (Ji et al 2002;Amaya et al 2004), whereas mRNA levels appear unaltered as shown by RNase protection (Ji et al 2002). The increase in TRPV1 immunoreactivity is prevented by neutralizing NGF with anti-NGF antisera.…”

Section: Ngf Is Involved In Embryonic Regulation Of Trp Channel Exprementioning

confidence: 90%

Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia

2009

View full text Add to dashboard Cite

Manipulation of neurotrophin (NT) signalling by administration or depletion of NTs, by transgenic overexpression or by deletion of genes coding for NTs and their receptors has demonstrated the importance of NT signalling for the survival and differentiation of neurons in sympathetic and dorsal root ganglia (DRG). Combination with mutation of the proapoptotic Bax gene allows the separation of survival and differentiation effects. These studies together with cell culture analysis suggest that NT signalling directly regulates the differentiation of neuron subpopulations and their integration into neural networks. The high-affinity NT receptors trkA, trkB and trkC are restricted to subpopulations of mature neurons, whereas their expression at early developmental stages largely overlaps. trkC is expressed throughout sympathetic ganglia and DRG early after ganglion formation but becomes restricted to small neuron subpopulations during embryogenesis when trkA is turned on. The temporal relationship between trkA and trkC expression is conserved between sympathetic ganglia and DRG. In DRG, NGF signalling is required not only for survival, but also for the differentiation of nociceptors. Expression of neuropeptides calcitonin gene-related peptide and substance P, which specify peptidergic nociceptors, depends on nerve growth factor (NGF) signalling. ret expression indicative of nonpeptidergic nociceptors is also promoted by the NGFsignalling pathway. Regulation of TRP channels by NGF signalling might specify the temperature sensitivity of afferent neurons embryonically. The manipulation of NGF levels "tunes" heat sensitivity in nociceptors at postnatal and adult stages. Brain-derived neurotrophic factor signalling is required for subpopulations of DRG neurons that are not fully characterized; it affects mechanical sensitivity in slowly adapting, low-threshold mechanoreceptors and might involve the regulation of DEG/ENaC ion channels. NT3 signalling is required for the generation and survival of various DRG neuron classes, in particular proprioceptors. Its importance for peripheral projections and central connectivity of proprioceptors demonstrates the significance of NT signalling for integrating responsive neurons in neural networks. The molecular targets of NT3 signalling in proprioceptor differentiation remain to be characterized. In sympathetic ganglia, NGF signalling regulates dendritic development and axonal projections. Its role in the specification of other neuronal properties is less well analysed. In vitro analysis suggests the involvement of NT signalling in the choice between the noradrenergic and cholinergic transmitter phenotype, in the expression of various classes of ion channels and for target connectivity. In vivo analysis is required to show the degree to which NT signalling regulates these sympathetic neuron properties in developing embryos and postnatally.

show abstract

“…Recently, Zhuang et al (2006) reported an uptake of the peptide inhibitor by DRG neurons after intrathecal injection, using Tat peptide. However, it is not clear how intrathecal anti-NGF is able to block what is assumed to be the influence of transported NGF, although the intrathecal route has been used to deliver molecules directly to DRG neurons including anti-NGF (Christensen and Hulsebosch, 1997;Amaya et al, 2004;Obata et al, 2004). Indeed, Reichardt and colleagues have reported that p38 MAPK activation occurs at the site of NGF binding to TrkA in the periphery (Huang and Reichardt, 2003).…”

Section: Discussion P75ntr Upregulation In the Adjacent Intact Drg Nementioning

confidence: 99%

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

Obata¹,

Katsura²,

Sakùrai³

et al. 2006

J. Neurosci.

View full text Add to dashboard Cite

The p75 neurotrophin receptor (p75NTR) has been implicated in diverse neuronal responses, including survival, cell death, myelination, and inhibition of regeneration. However, the role of p75NTR in neuropathic pain, for which there is currently no effective therapy, has not been explored. Here, we report that the pharmacological blockade of p75NTR in primary sensory neurons reversed neuropathic pain after nerve injury. Nerve injury increased the expression and axonal transport of p75NTR and phosphorylation of TrkA in the uninjured primary afferents. Functional inhibition of p75NTR suppressed injury-induced neuropathic pain and decreased the phosphorylation of TrkA and p38 mitogen-activated protein kinase, and the induction of transient receptor potential channels in dorsal root ganglion (DRG) neurons. Our results show that p75NTR induced in undamaged DRG neurons facilitates TrkA signaling and contributes to heat and cold hyperalgesia.

show abstract

NGF and GDNF differentially regulate TRPV1 expression that contributes to development of inflammatory thermal hyperalgesia

Cited by 216 publications

References 47 publications

TRPV1 Receptors in the CNS Play a Key Role in Broad-Spectrum Analgesia of TRPV1 Antagonists

TRPV1 Receptors in the CNS Play a Key Role in Broad-Spectrum Analgesia of TRPV1 Antagonists

Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia

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

Contact Info

Product

Resources

About