Behavioral and histological effects of endoneurial administration of nerve growth factor: possible implications in neuropathic pain

Barría, Guido Ruiz; Ceballos, Dolores; Baños, Josep-Eladi

doi:10.1016/j.brainres.2004.02.001

Cited by 41 publications

(28 citation statements)

References 29 publications

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“…Furthermore, more regenerated axons (sprouts) do not necessarily indicate more neurons regenerating (Piquilloud et al, 2007) and may be also considered deleterious in terms of functional recovery (Guntinas-Lichius et al, 2005). Hence, the increase of MF in the NGF groups would be in accordance with other studies that describe an important role of NGF on axonal sprouting (Diamond et al, 1987;Gloster et al, 1992;Ruiz et al, 2004). Thus, histological quantification of MFs may result in an overestimation of the number of regenerated neurons (Navarro 2015) and only the retrotracer study provides reliable information on the number of regenerating neurons.…”

Section: Discussionsupporting

confidence: 82%

Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

et al. 2016

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Neurotrophic factors (NTFs) promote nerve regeneration and neuronal survival after peripheral nerve injury. However, drawbacks related with administration and bioactivity during long periods limit their therapeutic application. In this study, PLGA microspheres (MPs) were used to locally release different NTFs and evaluate whether they accelerate axonal regeneration in comparison with free NTFs or controls. ELISA, SEM, UV/visible light microscopy, organotypic cultures of DRG explants and spinal cord slices were used to characterize MP properties and the bioactivity of the released NTFs. Results of organotypic cultures showed that encapsulated NTFs maintain longer bioactivity and enhance neurite regeneration of both sensory and motor neurons compared with free NTFs. For in vivo assays, the rat sciatic nerve was transected and repaired with a silicone tube filled with collagen gel or collagen mixed with PBS encapsulated MPs (control groups) and with free or encapsulated NGF, BDNF, GDNF or FGF-2. After 20 days, a retrotracer was applied to the regenerated nerve to quantify motor and sensory axonal regeneration. NTF encapsulation in MPs improved regeneration of both motor and sensory axons, as evidenced by increased numbers of retrolabeled neurons. Hence, our results show that slow release of NTFs with PLGA MP enhance nerve regeneration.

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Section: Discussionsupporting

confidence: 82%

Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

et al. 2016

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“…In the CCI model, an increase of NGF levels is observed in the cells of the injured area and in dorsal root ganglia at the level of the lesion, suggesting the involvement of NGF in the development of hyperalgesia in this model of neuropathic pain (24). Direct administration of NGF into the sciatic nerve induces hyperalgesia in rats (26), whereas NGF inhibition reduces thermal and mechanical hyperalgesia in CCI model (24,27,46), partial nerve transection (28) and partial transection of the spinal cord (47).…”

Section: Discussionmentioning

confidence: 89%

The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain

Ugolini¹,

Marinelli

Covaceuszach

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

114

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Nerve growth factor (NGF) is involved in pain transduction mechanisms and plays a key role in many persistent pain states, notably those associated with inflammation. On this basis, both the NGF ligand and its receptor TrkA (tyrosine kinase A) represent an eligible target for pain therapy. Although the direct involvement of NGF in pain modulation is well established, the effect of a direct functional block of the TrkA receptor is still unknown. In this study, we have demonstrated that MNAC13, the only anti-TrkA monoclonal antibody for which function neutralizing properties have been clearly shown both in vitro and in vivo, induces analgesia in both inflammatory and neuropathic pain models, with a surprisingly long-lasting effect in the latter. The formalin-evoked pain licking responses are significantly reduced by the MNAC13 antibody in CD1 mice. Remarkably, treatment with the anti-TrkA antibody also produces a significant antiallodynic effect on neuropathic pain: repeated i.p. injections of MNAC13 induce significant functional recovery in mice subjected to sciatic nerve ligation, with effects persisting after administration. Furthermore, a clear synergistic effect is observed when MNAC13 is administered in combination with opioids, at doses that are not efficacious per se. This study represents a direct demonstration that neutralizing antibodies directed against the TrkA receptor may display potent analgesic effects in inflammatory and chronic pain.analgesia ͉ behavior ͉ mice ͉ nerve growth factor

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“…The vehicle solution was a nonpotassium phosphate buffer (0.1 M pH 7.4), containing 0.1% of serum albumin. The dose of NGF was the lowest able to produce significant and reproducible heat hyperalgesia (Ruiz et al, 2004).…”

Section: Introductionmentioning

confidence: 95%

“…The maintenance of the phenotype of substance P-expressing neurons depends on Experimental work was carried out according to a protocol approved by the Ethics Committee for Animal and Human Research of the Universitat Autònoma de Barcelona, and was also in accordance with the Ethical Guidelines of the International Association for the Study of Pain (Zimmermann, 1983). Endoneurial injection was carried out as previously described (Ruiz, Ceballos, & Baños, 2004). Briefly, adult male Sprague-Dawley rats (250 g-300 g) were anesthetized with sodium pentobarbital (40 mg/kg i.p., supplemented as necessary).…”

Section: Introductionmentioning

confidence: 99%

Heat Hyperalgesia Induced by Endoneurial Nerve Growth Factor and the Expression of Substance P in Primary Sensory Neurons

Barría

Baños

2009

International Journal of Neuroscience

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Endoneurial nerve growth factor (30 ng) produced significant heat hyperalgesia in rats on postinjection days 3 and 5. The percentage of neuron profiles expressing the sensory neuropeptide substance P in the dorsal root ganglion (DRG), and the density and distribution of substance P immunoreactivity at the DRG and the dorsal horn remained essentially unchanged throughout the 10 days of study. NGF increased pain scores in the second phase of the formalin test on postinjection day 3, but not on days 5 and 10. Our results indicate that the observed heat hyperalgesia is not dependent on NGF-induced changes in SP content and release from primary sensory neurons.

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Behavioral and histological effects of endoneurial administration of nerve growth factor: possible implications in neuropathic pain

Cited by 41 publications

References 29 publications

Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain

Heat Hyperalgesia Induced by Endoneurial Nerve Growth Factor and the Expression of Substance P in Primary Sensory Neurons

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