Cellular and molecular insights into neuropathy-induced pain hypersensitivity for mechanism-based treatment approaches

Berger, Julie; Knaepen, Liesbeth; Janssen, Sofie; Jaken, R.; Marcus, Marco A. E.; Joosten, Elbert A.J.; Deumens, Ronald

doi:10.1016/j.brainresrev.2011.03.003

Cited by 74 publications

(59 citation statements)

References 337 publications

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“…On the basis of these data, we conclude that these structural changes are not a main player in the onset of mechanical pain hypersensitivity following nerve injury. However, it needs to be stressed that our study focused exclusively on mechanical hypersensitivity, which is one of the most debilitating features of neuropathic pain (Berger et al, 2011). Therefore we cannot exclude that the structural changes we observed in the superficial spinal dorsal horn may to some extent be related to other modalities such as cold and heat hypersensitivity.…”

Section: Spinal Gap-43 Expression and Nerve Injurymentioning

confidence: 87%

“…It is thought that more effective and specific treatment approaches may be based on neuropathic pain mechanisms (Baron et al, 2010). Therapeutic targets have been identified by the progress made in elucidating cellular and/or molecular mechanisms contributing to neuropathy-induced pain hypersensitivity (Basbaum et al, 2009;Berger et al, 2011;Ren and Dubner, 2010). After a focus on the mechanisms involved in the onset of pain hypersensitivity following nerve injury, more and more attention is being given to describing the mechanisms that are responsible for pain chronicity (Eijkelkamp et al, 2010;Ji et al, 2006;Marchand et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Spinal Gap-43 Expression and Nerve Injurymentioning

confidence: 87%

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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“…Both allodynia-and CGRP/GAP43-positive afferent sprouting were lower in the GDNF-transfected group compared with the NSC alone. Non-directed axonal sprouting might also cause (Berger et al, 2011). Kalous et al provided evidence that the anatomical reorganization of sensory and nociceptive dorsal horn circuits rostral to an injury could factor in the development or maintenance of SCI pain (Kalous et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Injectable alginate hydrogel loaded with GDNF promotes functional recovery in a hemisection model of spinal cord injury

Ansorena

Berdt

Ucakar

et al. 2013

International Journal of Pharmaceutics

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We hypothesized that local delivery of GDNF in spinal cord lesion via an injectable alginate hydrogel gelifying in situ would support spinal cord plasticity and functional recovery. The GDNF release from the hydrogel was slowed by GDNF encapsulation in microspheres compared to non-formulated GDNF (free GDNF). When injected in a rat spinal cord hemisection model, more neurofilaments were observed in the lesion when the rats were treated with free GDNF-loaded hydrogels. More growing neurites were detected in the tissues surrounding the lesion when the animals were treated with GDNF microsphere-loaded hydrogels. Intense GFAP (astrocytes), low βIII tubulin (neural cells) and RECA-1 (endothelial cells) stainings were observed for non-treated lesions while GDNF-treated spinal cords presented less GFAP staining and more endothelial and nerve fiber infiltration in the lesion site. The animals treated with free GDNF-loaded hydrogel presented superior functional recovery compared with the animals treated with the GDNF microsphere-loaded hydrogels and non-treated animals.

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“…The development of chronic pain following surgery correlates with the presence of peripheral nerve injury (Macrae, 2001). Studies using various peripheral nerve injury models have shown that these models share some, but not all, of the injury-induced molecular changes that may be contributing to chronic neuropathic pain (Berger et al, 2011;Xu and Yaksh, 2011). Moreover, whether changes in a given molecule contribute to neuropathic pain also appears to depend in their anatomical location (neuroma at the site of the peripheral nerve injury, dorsal root ganglia somata, spinal cord etc).…”

Section: Introductionmentioning

confidence: 99%

An Approach to Identify Nerve Injury-Evoked Changes that Contribute to the Development or Protect Against the Development of Sustained Neuropathic Pain

Recio-Pinto¹,

Norcini²,

Blanck³

2012

Basic Principles of Peripheral Nerve Disorders

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Cellular and molecular insights into neuropathy-induced pain hypersensitivity for mechanism-based treatment approaches

Cited by 74 publications

References 337 publications

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

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

Injectable alginate hydrogel loaded with GDNF promotes functional recovery in a hemisection model of spinal cord injury

An Approach to Identify Nerve Injury-Evoked Changes that Contribute to the Development or Protect Against the Development of Sustained Neuropathic Pain

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