Effects of systemically administered NT‐3 on sensory neuron loss and nestin expression following axotomy

Kuo, Lu-Ting; Simpson, Andrew J. H.; Schänzer, Anne; Tse, Jamie; An, Shu-Feng; Salvatore, Francesco; Groves, Michael J.

doi:10.1002/cne.20400

Cited by 38 publications

(32 citation statements)

References 62 publications

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“…Unlike p38, JNK is only activated in injured neurons [82,92]. JNK activation in DRG neurons is not associated with apoptosis, because neuronal apoptosis after nerve injury is not noticeable in the first several weeks [93]. Instead, the transient JNK activation is involved in the early development of mechanical allodynia after nerve injury, because DRG infusion of the peptide JNK inhibitor D-JNKI-1 prevents mechanical allodynia for a week but does not reverse mechanical allodynia [92].…”

Section: Mapk Signaling Pathways and Peripheral Sensitizationmentioning

confidence: 98%

Intracellular Signaling in Primary Sensory Neurons and Persistent Pain

2008

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During evolution, living organisms develop a specialized apparatus called nociceptors to sense their environment and avoid hazardous situations. Intense stimulation of high threshold C- and Adelta-fibers of nociceptive primary sensory neurons will elicit pain, which is acute and protective under normal conditions. A further evolution of the early pain system results in the development of nociceptor sensitization under injury or disease conditions, leading to enhanced pain states. This sensitization in the peripheral nervous system is also called peripheral sensitization, as compared to its counterpart, central sensitization. Inflammatory mediators such as proinflammatory cytokines (TNF-alpha, IL-1beta), PGE(2), bradykinin, and NGF increase the sensitivity and excitability of nociceptors by enhancing the activity of pronociceptive receptors and ion channels (e.g., TRPV1 and Na(v)1.8). We will review the evidence demonstrating that activation of multiple intracellular signal pathways such as MAPK pathways in primary sensory neurons results in the induction and maintenance of peripheral sensitization and produces persistent pain. Targeting the critical signaling pathways in the periphery will tackle pain at the source.

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Section: Mapk Signaling Pathways and Peripheral Sensitizationmentioning

confidence: 98%

Intracellular Signaling in Primary Sensory Neurons and Persistent Pain

2008

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“…A consensus exists that target removal or irreversible damage to a peripheral sensory nerve brings about neuronal loss in the DRGs. However, reported quantitative data show large variability, consistent with the multifactorial dependence of neurons for survival after axotomy, such as animal age, nerve type, distance of tran-section from the soma, availability of trophic factors, and postlesion survival time (Ljungberg et al, 1999;McKay et al, 2002;Kuo et al, 2005;Zhou et al, 2005). A major and often neglected additional factor is the method used for quantitation (Tandrup et al, 2000), as well as the normal occurrence of side differences in neuron number in the DRG (Ygge et al, 1981;Avendaño and Lagares, 1996).…”

Section: Introductionmentioning

confidence: 93%

Primary Sensory Neuron Addition in the Adult Rat Trigeminal Ganglion: Evidence for Neural Crest Glio-Neuronal Precursor Maturation

Lagares¹,

Li²,

Zhou³

et al. 2007

J. Neurosci.

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It is debated whether primary sensory neurons of the dorsal root ganglia increase the number in adult animals and, if so, whether the increase is attributable to postnatal neurogenesis or maturation of dormant, postmitotic precursors. Similar studies are lacking in the trigeminal ganglion (TG). Here we demonstrate by stereological methods that the number of neurons in the TG of adult male rats nearly doubles between the third and eighth months of age. The increase is mainly attributable to the addition of small, B-type neurons, with a smaller contribution of large, A-neurons. We looked for possible proliferative or maturation mechanisms that could explain this dramatic postnatal expansion in neuron number, using bromodeoxyuridine (BrdU) labeling, immunocytochemistry for neural precursor cell antigens, retrograde tracing identification of peripherally projecting neurons, and in vitro isolation of precursor cells from adult TG explant cultures. Cell proliferation identified months after an extended BrdU administration was sparse and essentially corresponded to glial cells. No BrdU-labeled cell took up the peripherally injected tracer, and only a negligible number coexpressed BrdU and the pan-neuronal tracer neuron-specific enolase. In contrast, a population of cells not recognizable as mature neurons in the TG and neighboring nerve expressed neuronal precursor antigens, and neural crest glioneuronal precursor cells were successfully isolated from adult TG explants. Our data suggest that a protracted maturation process persists in the TG that can be responsible for the neuronal addition found in the adult rat.

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“…We utilised this model in conjunction with laser microdissection and qRT-PCR in order to highlight the diVerential transcriptional response of MG and sural neuron subpopulations following injury. Whilst activated caspase-3 protein has been identiWed in morphologically apoptotic DRG neurons following distal axotomy (Kuo et al 2005), our Wndings demonstrate that axotomised MG neurons signiWcantly downregulate caspase-3 mRNA whereas the axotomised sural neurons signiWcantly upregulate caspase-3 transcripts at 1 week post-injury. This disparate response to injury is likely to be attributable to the diVering IB4-positive composition of the subpopulations described.…”

Section: Discussionmentioning

confidence: 85%

“…Following peripheral axotomy morphologically apoptotic DRG neurons demonstrate immunoreactivity for activated caspase-3 protein (Kuo et al 2005), and the proportion of IB4-positive neurons decreases in the axotomised DRG (Bradbury et al 1998;McMahon and Moore 1988). Therefore, we were keen to investigate the relationship between neurochemical phenotype and apoptotic expression in functionally diVering DRG subpopulations.…”

Section: Introductionmentioning

confidence: 98%

Phenotype of distinct primary sensory afferent subpopulations and caspase-3 expression following axotomy

Reid

Mantovani

Shawcross

et al. 2011

Histochem Cell Biol

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Specific sensory neuronal subpopulations show contrasting responses to peripheral nerve injury, as shown by the axotomy-induced death of many cutaneous sensory neurons whilst muscular sensory afferents survive an identical insult. We used a novel combination of retrograde neuronal tracing with immunohistochemistry and laser microdissection techniques, in order to describe the neurochemistry of medial gastrocnemius (muscular sensory afferents) and sural (cutaneous sensory afferents) branches of the rat sciatic nerve and relate this to the pro-apoptotic caspase-3 gene expression following nerve transection. Our results demonstrated distinctions in medial gastrocnemius and sural neuron populations with the most striking difference in the respective proportions of isolectin B4 (IB4) staining neurons (3.7 V 32.8%). The mean neuronal area of the medial gastrocnemius (MG) neurons was larger than that of the sural (SUR) neurons (1,070.8 V 646.2 μm²) and each phenotypic group was significantly smaller in sural neurons than in MG neurons. At 1 week post-axotomy, MG neurons markedly downregulated caspase-3, whilst SUR neurons upregulated caspase-3 gene expression; this may be attributable to the differing IB4-positive composition of the subpopulations. These findings provide further clarification in the understanding of two distinct neuronal populations used increasingly in nerve injury models.

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Effects of systemically administered NT‐3 on sensory neuron loss and nestin expression following axotomy

Cited by 38 publications

References 62 publications

Intracellular Signaling in Primary Sensory Neurons and Persistent Pain

Intracellular Signaling in Primary Sensory Neurons and Persistent Pain

Primary Sensory Neuron Addition in the Adult Rat Trigeminal Ganglion: Evidence for Neural Crest Glio-Neuronal Precursor Maturation

Phenotype of distinct primary sensory afferent subpopulations and caspase-3 expression following axotomy

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