Nociceptor-derived brain-derived neurotrophic factor regulates acute and inflammatory but not neuropathic pain

Zhao, Jing; Seereeram, Anjan; Nassar, Mohammed A.; Levato, Alessandra; Pezet, Sophie; Hathaway, Gareth; Morenilla‐Palao, Cruz; Stirling, Caroline L.; Fitzgerald, Maria; McMahon, Stephen B.; Rios, Maribel; Wood, John N.

doi:10.1016/j.mcn.2005.11.008

Cited by 152 publications

(142 citation statements)

References 44 publications

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“…We intrathecally administered dihydro-S1P and determined its effect on the PKA-dependent phosphorylation of the NMDA receptor subunit 1 (NR1) on serine 897. In accordance with previous reports NR1 phosphorylation on serine 897 in the outer laminae of the dorsal horn was increased in the formalin assay (40,41) (Fig. 6, A and B).…”

Section: Dihydro-s1p Inhibits the Campdependent Phosphorylation Of Nmsupporting

confidence: 93%

“…This NMDA receptor phosphorylation is enhanced during the second phase of the formalin assay and serves to sensitize NMDA receptors in the dorsal horn (40,41). We intrathecally administered dihydro-S1P and determined its effect on the PKA-dependent phosphorylation of the NMDA receptor subunit 1 (NR1) on serine 897.…”

Section: Dihydro-s1p Inhibits the Campdependent Phosphorylation Of Nmmentioning

confidence: 99%

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Sphingosine 1-Phosphate Modulates Spinal Nociceptive Processing

Coste

Brenneis

Linke

et al. 2008

Journal of Biological Chemistry

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Sphingosine 1-Phosphate (S1P) modulates various cellular functions such as apoptosis, cell differentiation, and migration. Although S1P is an abundant signaling molecule in the central nervous system, very little is known about its influence on neuronal functions. We found that S1P concentrations were selectively decreased in the cerebrospinal fluid of adult rats in an acute and an inflammatory pain model. Pharmacological inhibition of sphingosine kinases (SPHK) decreased basal pain thresholds and SphK2 knock-out mice, but not SphK1 knock-out mice, had a significant decrease in withdrawal latency. Intrathecal application of S1P or sphinganine 1-phosphate (dihydro-S1P) reduced the pain-related (nociceptive) behavior in the formalin assay. S1P and dihydro-S1P inhibited cyclic AMP (cAMP) synthesis, a key second messenger of spinal nociceptive processing, in spinal cord neurons. By combining fluorescence resonance energy transfer (FRET)-based cAMP measurements with Multi Epitope Ligand Cartography (MELC), we showed that S1P decreased cAMP synthesis in excitatory dorsal horn neurons. Accordingly, intrathecal application of dihydro-S1P abolished the cAMP-dependent phosphorylation of NMDA receptors in the outer laminae of the spinal cord. Taken together, the data show that S1P modulates spinal nociceptive processing through inhibition of neuronal cAMP synthesis.The bioactive sphingolipid metabolite sphingosine 1-phosphate (S1P) 2 is synthesized by phosphorylation of sphingosine by sphingosine kinases (SPHK) in a wide variety of cell types in response to extracellular stimuli such as nerve growth factor or vascular endothelial growth factor. S1P modulates diverse cellular functions such as apoptosis, cell differentiation, and migration either through the activation of a family of five G-protein-coupled receptors (S1P 1-5 ) or by acting as an intracellular second messenger (1-3). In the central nervous system S1P has been shown to be released by cerebellar granule cells and astrocytes (4 -6). Regarding its function in the central nervous system it is well known that S1P promotes survival of neurons and astrocytes, induces proliferation of neural progenitor cells and astrocytes, and mediates nerve growth factor (NGF)-stimulated neurite outgrowth (2, 3, 7). However, very little is known about the role of S1P in the regulation of neuronal excitability and the mechanisms that mediate these S1P functions. Recently whole cell patch clamp recordings revealed that loss of S1P 2 leads to a large increase in the excitability of neocortical pyramidal neurons (8), suggesting an inhibitory effect of S1P 2 on neuronal excitability. On the other hand, several in vitro studies show that S1P can also increase neuronal functions. For example, S1P receptor activation augments glutamate secretion in hippocampal neurons (9) and elevated intracellular S1P concentrations enhance the spontaneous neurotransmitter release at neuromuscular junctions (10). Furthermore, intra-as well as extracellularly applied S1P facilitated the NGF-induced increas...

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Section: Dihydro-s1p Inhibits the Campdependent Phosphorylation Of Nmsupporting

confidence: 93%

Section: Dihydro-s1p Inhibits the Campdependent Phosphorylation Of Nmmentioning

confidence: 99%

Sphingosine 1-Phosphate Modulates Spinal Nociceptive Processing

Coste

Brenneis

Linke

et al. 2008

Journal of Biological Chemistry

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“…However, it has yet to be shown that resident microglia in the spinal cord respond to nerve injury by releasing BDNF. In mice, where BDNF was genetically eliminated from small diameter sensory neurons, inflammatory pain was significantly attenuated but development of allodynia following nerve injury was unperturbed [87]. This finding is consistent with primary afferent derived BDNF not having a causal role in the sequelae of neurpathic pain arising from injury to a peripheral nerve.…”

Section: Introductionsupporting

confidence: 67%

P2X4 purinoceptor signaling in chronic pain

Trang

Salter

2012

Purinergic Signalling

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ATP, acting via P2 purinergic receptors, is a known mediator of inflammatory and neuropathic pain. There is increasing evidence that the ATP-gated P2X4 receptor (P2X4R) subtype is a locus through which activity of spinal microglia and peripheral macrophages instigate pain hypersensitivity caused by inflammation or by injury to a peripheral nerve. The present article highlights the recent advances in our understanding of microglia-neuron interactions in neuropathic pain by focusing on the signaling and regulation of the P2X4R. We will also develop a framework for understanding converging lines of evidence for involvement of P2X4Rs expressed on macrophages in peripheral inflammatory pain.

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“…actions of these mediators. Killing the dorsal horn neurons that express NK1 receptors suppresses allodynia, and deleting the gene for BDNF in Nav1.8 ϩ neurons also inhibits central sensitization (18,19). Specific antagonists of TRPV1 can block mechanical allodynia, suggesting that presynaptic TRPV1 activation is an important element in the release of proallodynic mediators (20).…”

Section: Mechanisms Of Allodyniamentioning

confidence: 99%