Reorganization of central terminals of myelinated primary afferents in the rat dorsal horn following peripheral axotomy

Woolf, Clifford J.; Shortland, Peter; Reynolds, M. L.; Ridings, J.; Doubell, Timothy P.; Coggeshall, Richard E.

doi:10.1002/cne.903600109

Cited by 265 publications

(220 citation statements)

References 45 publications

(50 reference statements)

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“…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

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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.

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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

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“…It is likely that the mechanisms of pain chronicity develop in the early stages after nerve injury. Indeed, structural plasticity in the nociceptive network, which is considered an important contributor to chronicity of neuropathic pain symptoms such as mechanical pain hypersensitivity, occurs within days after nerve injury (Doubell et al, 1997;Shortland et al, 1997;Woolf et al, 1992Woolf et al, ,1995.…”

Section: Introductionmentioning

confidence: 99%

Neuropathy-Induced Spinal GAP-43 Expression Is Not a Main Player in the Onset of Mechanical Pain Hypersensitivity

Jaken

Gorp

Joosten

et al. 2011

Journal of Neurotrauma

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Structural plasticity within the spinal nociceptive network may be fundamental to the chronic nature of neuropathic pain. In the present study, the spatiotemporal expression of growth-associated protein-43 (GAP-43), a protein which has been traditionally implicated in nerve fiber growth and sprouting, was investigated in relation to mechanical pain hypersensitivity. An L5 spinal nerve transection model was validated by the presence of mechanical pain hypersensitivity and an increase in the early neuronal activation marker cFos within the superficial spinal dorsal horn upon innocuous hindpaw stimulation. Spinal GAP-43 was found to be upregulated in the superficial L5 dorsal horn from 5 up to 10 days after injury. GAP-43 was co-localized with calcitoningene related peptide (CGRP), but not vesicular glutamate transporter-1 (VGLUT-1), IB4, or protein kinase-c (PKC-c), suggesting the regulation of GAP-43 in peptidergic nociceptive afferents. These GAP-43/CGRP fibers may be indicative of sprouting peptidergic fibers. Fiber sprouting largely depends on growth factors, which are typically associated with neuro-inflammatory processes. The putative role of neuropathy-induced GAP-43 expression in the development of mechanical pain hypersensitivity was investigated using the immune modulator propentofylline. Propentofylline treatment strongly attenuated the development of mechanical pain hypersensitivity and glial responses to nerve injury as measured by microglial and astroglial markers, but did not affect neuropathy-induced levels of spinal GAP-43 or GAP-43 regulation in CGRP fibers. We conclude that nerve injury induces structural plasticity in fibers expressing CGRP, which is regarded as a main player in central sensitization. Our data do not, however, support a major role of these structural changes in the onset of mechanical pain hypersensitivity.

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“…Tactile allodynia is induced by activation of various types of fibers after damage to a peripheral nerve (52,53 In conclusion, dorsal rhizotomy of the brachial plexus represents a good experimental model for studying the changes which take place in the central and peripheral nervous system after damage, together with the mechanisms that inhibit regeneration, and therapeutic strategies that can be used to guide regenerating axons through inhibitory environments towards synaptic fields appropriate for recovery of lost function.…”

Section: Discussionmentioning

confidence: 99%

“…Tactile allodynia is induced by activation of various types of fibers after damage to a peripheral nerve (52,53). The allodynia is evident as a marked hypersensitivity to stimuli which under normal conditions would induce an innocuous sensation.…”

Section: Discussionmentioning

confidence: 99%

“…The adequate force to cause the lesion is not established and is therefore a subjective parameter. In conclusion, reproducibility of our extensive rhizotomy lesion, the study of different type of primary afferents in both the root and the dorsal horn, and the differences between spinal segments guarantee our experimental model of brachial plexus avulsion.Tactile allodynia is induced by activation of various types of fibers after damage to a peripheral nerve (52,53 In conclusion, dorsal rhizotomy of the brachial plexus represents a good experimental model for studying the changes which take place in the central and peripheral nervous system after damage, together with the mechanisms that inhibit regeneration, and therapeutic strategies that can be used to guide regenerating axons through inhibitory environments towards synaptic fields appropriate for recovery of lost function. …”

mentioning

confidence: 99%

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Degeneración de los terminales aferentes primarios de rata luego de lesión extensa por avulsión del plexo braquial

et al. 2004

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Important breakthroughs in the understanding regeneration failure in an injured CNS have been made by studies of primary afferent neurons. Dorsal rhizotomy has provided an experimental model of brachial plexus (BP) avulsion. This is an injury in which the central branches of primary afferents are disrupted at their point of entry into the spinal cord, bringing motor and sensory dysfunction to the upper limbs. In the present work, the central axonal organization of primary afferents was examined in control (without lesion) adult Wistar rats and in rats subjected to a C3-T3 rhizotomy. Specific sensory axon subtypes were recognized by application of antibodies to the calcitonin gene-related peptide (CGRP), the P2X3 purinoreceptor, the low-affinity p75-neurotrophin receptor and the retrograde tracer cholera toxin subunit β (TCβ). Other subtypes weres labeled with the lectin Griffonia simplicifolia IB4. Using immunohistochemistry and high resolution light microscopy, brachial plexus rhizotomy in adult rats has proven a reliable model for several neural deficits in humans. This lesion produced different degrees of terminal degeneration in the several types of primary afferents which define sub-populations of sensitive neurons. Between the C6 and C8 levels of the spinal cord,, deafferentation was partial for peptidergic GCRP-positive fibers, in contrast with elimination of non peptidergic and myelinated fibers. Dorsal rhizotomy has provided an adequate experimental model to study sensory alterations such as acute pain and allodynia as well as factors that affect regeneration into the CNS., Therefore, the differential deafferentation response must be considered inr the evaluation of therapies for nociception (pain) and regeneration for brachial plexus avulsion. The anatomical diffierences among the primary afferent subtypes also affect their roles in normal and damaged conditions. Key words: primary afferents, cervical spinal cord, dorsal root avulsion, lectin Griffonia simplicifolia (IB4), cholera toxin subunit b (CTβ), calcitonin gene-related peptide (CGRP), purinoreceptor (P2X3). Degeneración de los terminales aferentes primarios de rata luego de lesión extensa por avulsión del plexo braquialEl uso de las neuronas sensoriales primarias ha aportado avances en el entendimiento de las razones por las cuales falla la regeneración cuando el sistema nervioso central (SNC) es dañado. La rizotomía dorsal se puede usar como un modelo experimental de las lesiones por avulsión del plexo braquial, una lesión en la cual son desprendidas, en su punto de entrada en la médula espinal, las ramas centrales de los aferentes primarios causando una disfunción motora y sensorial grave e irreversible del miembro superior. En el presente trabajo, se examinó la organización central de los aferentes primarios en ratas Wistar adultas. Éstas fueron divididas en controles normales no lesionados y en animales rizotomizados entre los niveles cervical 3 y torácico 3 (C3-T3). Se estudió la deaferentación de los subtipos de axones sensoriales utiliza...

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Reorganization of central terminals of myelinated primary afferents in the rat dorsal horn following peripheral axotomy

Cited by 265 publications

References 45 publications

Analyzing Somatosensory Axon Projections with the Sensory Neuron-SpecificAdvillinGene

Analyzing Somatosensory Axon Projections with the Sensory Neuron-SpecificAdvillinGene

Neuropathy-Induced Spinal GAP-43 Expression Is Not a Main Player in the Onset of Mechanical Pain Hypersensitivity

Degeneración de los terminales aferentes primarios de rata luego de lesión extensa por avulsión del plexo braquial

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