Central changes in primary afferent fibers following peripheral nerve lesions

Coggeshall, Richard E.; Lekan, Helena A.; Doubell, Timothy P.; Allchorne, Andrew; Woolf, Clifford J.

doi:10.1016/s0306-4522(96)00528-3

Cited by 66 publications

(40 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is an intriguing possibility that the microglial activation is driven by altered C-fibre input as a consequence of peripheral nerve injury as has been previously proposed (Mannion et al, 1996(Mannion et al, , 1998. Unmyelinated C-fibres have been shown to be more susceptible to peripheral nerve injury, with a large percentage of unmyelinated cells dying following peripheral nerve injury (Coggeshall et al, 1997) and further studies will be required to ascertain whether the microglial response is indicative of the first stage of degeneration of unmyelinated primary afferents following peripheral nerve injury.…”

Section: Somatotopymentioning

confidence: 90%

Stereological and somatotopic analysis of the spinal microglial response to peripheral nerve injury

Beggs

Salter

2007

Brain, Behavior, and Immunity

129

View full text Add to dashboard Cite

The involvement of glia, and glia-neuronal signalling in enhancing nociceptive transmission has become an area of intense scientific interest. In particular, a role has emerged for activated microglia in the development and maintenance of neuropathic pain following peripheral nerve injury. Following activation, spinal microglia proliferate and release many substances which are capable of modulating neuronal excitability within the spinal cord. Here, we the investigated the response of spinal microglia to a unilateral spared nerve injury (SNI) in terms of the quantitative increase in cell number and the spatial distribution of the increase. Design-based stereological techniques were combined with iba-1 immunohistochemistry to estimate the total number of microglia in the spinal dorsal horn in naïve and peripheral nerve-injured adult rats. In addition, by mapping the central terminals of hindlimb nerves, the somatotopic distribution of the microglial response was mapped. Following SNI there was a marked increase in the number of spinal microglia: The total number of microglia (mean ± SD) in the dorsal horn sciatic territory of the naïve rat was estimated to be 28,591 ± 2715. Following SNI the number of microglia was 82,034 ± 8828. While the pattern of microglial activation generally followed somatotopic boundaries, with the majority of microglia within the territory occupied by peripherally axotomised primary afferents, some spread was seen into regions occupied by intact, 'spared' central projections of the sural nerve. This study provides a reproducible method of assaying spinal microglial dynamics following peripheral nerve injury both quantitatively and spatially.

show abstract

Section: Somatotopymentioning

confidence: 90%

Stereological and somatotopic analysis of the spinal microglial response to peripheral nerve injury

Beggs

Salter

2007

Brain, Behavior, and Immunity

129

View full text Add to dashboard Cite

show abstract

“…Confirmation that the actual number of neurons was similar in p73ϩ/ϩ versus p73ϩ/Ϫ L4 DRGs was obtained by quantitating axons in dorsal root transverse sections using electron microscopy, a method that provides a reliable index of neuronal number in the L4 DRG (Coggeshall et al, 1997). This analysis revealed that p73ϩ/ϩ and p73ϩ/Ϫ dorsal roots contain 3411 Ϯ 170 (n ϭ 3) and 3301 Ϯ 179 (n ϭ 3) unmyelinated and 2376 Ϯ 104 (n ϭ 3) and 2335 Ϯ 131 (n ϭ 3) myelinated axons, respectively, numbers that were statistically similar between the genotypes (Fig.…”

Section: B)mentioning

confidence: 95%

The Invulnerability of Adult Neurons: A Critical Role for p73

Walsh

Orike²,

Kaplan³

et al. 2004

J. Neurosci.

View full text Add to dashboard Cite

Here, we investigated the intracellular mechanisms that underlie the relative invulnerability of adult versus developing dorsal root ganglion (DRG) sensory neurons. In culture, adult neurons were resistant to stimuli that caused apoptosis of their neonatal counterparts. In both adult and neonatal neurons, death stimuli induced the apoptotic c-Jun N-terminal protein kinase (JNK) pathway, but JNK activation only caused death of neonatal neurons, indicating that adult neurons have a downstream block to apoptosis. Expression of the dominant-inhibitory p53 family member, ⌬Np73, rescued JNK-induced apoptosis of neonatal neurons, suggesting that it might participate in the downstream apoptotic block in adult neurons. To test this possibility, we examined adult DRG neurons cultured from p73ϩ/Ϫ mice. Adult p73ϩ/Ϫ DRG neurons were more vulnerable to apoptotic stimuli than their p73ϩ/ϩ counterparts, and invulnerability could be restored to the p73ϩ/Ϫ neurons by increased expression of ⌬Np73. Moreover, although DRG neuron development was normal in p73ϩ/Ϫ animals in vivo, axotomy caused death of adult p73ϩ/Ϫ but not p73ϩ/ϩ DRG neurons. Thus, one way adult neurons become invulnerable is to enhance endogenous survival pathways, and one critical component of these survival pathways is p73.

show abstract

“…We noted that the central axons appear more stable and less plastic after peripheral lesion in Advillin-deficient mice. In this respect, we speculate that inhibiting the activity of Advillin protein might be beneficiary for preventing the development of neuropathic pain because ectopic sprouting of axon termini in the dorsal horn of the spinal cord was implicated as one underlying mechanism of neuropathic pain (Woolf et al, 1992(Woolf et al, , 1995Coggeshall et al, 1997).…”

Section: Physiological Functions Of Advillin In the Somatic Sensory Smentioning

confidence: 99%

Analyzing Somatosensory Axon Projections with the Sensory Neuron-SpecificAdvillinGene

Hasegawa¹,

Abbott²,

Han³

et al. 2007

J. Neurosci.

151

173

View full text Add to dashboard Cite

Peripheral sensory neurons detect diverse physical stimuli and transmit the information into the CNS. At present, the genetic tools for specifically studying the development, plasticity, and regeneration of the sensory axon projections are limited. We found that the gene encoding Advillin, an actin binding protein that belongs to the gelsolin superfamily, is expressed almost exclusively in peripheral sensory neurons. We next generated a line of knock-in mice in which the start codon of the Advillin is replaced by the gene encoding human placenta alkaline phosphatase (Avil-hPLAP mice). In heterozygous Avil-hPLAP mice, sensory axons, the exquisite sensory endings, as well as the fine central axonal collaterals can be clearly visualized with a simple alkaline phosphatase staining. Using this mouse line, we found that the development of peripheral target innervation and sensory ending formation is an ordered process with specific timing depending on sensory modalities. This is also true for the in-growth of central axonal collaterals into the brainstem and the spinal cord. Our results demonstrate that Avil-hPLAP mouse is a valuable tool for specifically studying peripheral sensory neurons. Functionally, we found that the regenerative axon growth of Advillin-null sensory neurons is significantly shortened and that deletion of Advillin reduces the plasticity of whisker-related barrelettes patterns in the hindbrain.

show abstract

Central changes in primary afferent fibers following peripheral nerve lesions

Cited by 66 publications

References 74 publications

Stereological and somatotopic analysis of the spinal microglial response to peripheral nerve injury

Stereological and somatotopic analysis of the spinal microglial response to peripheral nerve injury

The Invulnerability of Adult Neurons: A Critical Role for p73

Analyzing Somatosensory Axon Projections with the Sensory Neuron-SpecificAdvillinGene

Contact Info

Product

Resources

About