Intrathecal NGF Administration Reduces Reactive Astrocytosis and Changes Neurotrophin Receptors Expression Pattern in a Rat Model of Neuropathic Pain

Cirillo, Giovanni; Cavaliere, Carlo; Bianco, Mimma; Simone, Antonietta; Colangelo, Anna Maria; Sellitti, Stefania; Alberghina, Lilia; Papa, Michèle

doi:10.1007/s10571-009-9430-2

Cited by 70 publications

(48 citation statements)

References 42 publications

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“…Several experiments in rat models have shown that administration of growth factors, including NGF and NGF-mimetic factors, help to reduce symptoms of neuropathic pain. 18,19 NGF plays a role in survival, differentiation, and growth of sensory and sympathetic neurons. 33,34 NGF has, further, a direct effect on regeneration of neurons and restoring function in injured neuronal cells.…”

Section: Discussionmentioning

confidence: 99%

“…This rationale is based on reports on the use of neurotrophic factors, particularly nerve growth factor ( NGF ) to reduce allodynia in animal models with neuropathic pain. 18,19 By reducing reactive astrocytosis and reversing the glial morphomolecular modulation, NGF reduces both allodynia and hyperalgesia. Administration of neurotrophic factors results in post-injury repair of peripheral nerves and their functional recovery.…”

Section: Introductionmentioning

confidence: 99%

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Autologous Serum Tears for Treatment of Photoallodynia in Patients with Corneal Neuropathy: Efficacy and Evaluation with In Vivo Confocal Microscopy

et al. 2015

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Objective Patients suffering from corneal neuropathy may present with photoallodynia; i.e., increased light sensitivity, frequently with a normal slit-lamp examination. This study aimed to evaluate the efficacy of autologous serum tears (AST) for treatment of severe photoallodynia in corneal neuropathy and correlate with corneal subbasal nerve alterations by in vivo confocal microscopy (IVCM). Methods Retrospective case control study with 16 patients with neuropathy-induced severe photoallodynia compared to 16 normal controls. Symptom severity, clinical examination and bilateral corneal IVCM scans were recorded. Results All patients suffered from extreme photoallodynia (8.8±1.1) with no concurrent ocular surface disease. Subbasal nerves were significantly decreased at baseline in patients compared to controls; total nerve length (9208 ±1264 vs 24714 ±1056 μm/mm2; p<.0001) and total nerve number (9.6±1.4 vs 28.6±2.0; p<.0001), respectively. Morphologically, significantly increased reflectivity (2.9±0.2 vs 1.8±0.1; p<.0001), beading (in 93.7%), and neuromas (in 62.5%) were seen. AST (3.6±2.1 months) resulted in significantly decreased symptom severity (1.6±1.7; p=.02). IVCM demonstrated significantly improved nerve parameters (p< .005), total nerve length (15451±1595 μm/mm2), number (13.9±2.1), and reflectivity (1.9±0.1). Beading and neuromas were seen in only 56.2% and 7.6% of patients. Conclusion Patients with corneal neuropathy-induced photoallodynia show profound alterations in corneal nerves. AST restores nerve topography through nerve regeneration, and this correlated with improvement in patient-reported photoallodynia. The data support the notion that corneal nerve damage results in alterations in afferent trigeminal pathways to produce photoallodynia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Autologous Serum Tears for Treatment of Photoallodynia in Patients with Corneal Neuropathy: Efficacy and Evaluation with In Vivo Confocal Microscopy

et al. 2015

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“…We have previously reported that PNI correlates with changes of fiber density in the dorsal horn of lumbar spinal cord and increase of glial markers indicative of reactive astrogliosis (Cirillo et al 2010(Cirillo et al , 2011Colangelo et al 2008). The neuro-glial network rearrangement in spinal circuitry was studied with the SNI model of PNI to induce early and persistent reactive gliosis, disrupte the PNNs, and investigate its role in perturbing synaptic homeostasis.…”

Section: Microglia Activation and Reactive Gliosis In Ventral Horn Ofmentioning

confidence: 99%

Astrocytes and Microglia-Mediated Immune Response in Maladaptive Plasticity is Differently Modulated by NGF in the Ventral Horn of the Spinal Cord Following Peripheral Nerve Injury

et al. 2015

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Reactive astrocytes and activated microglia are the key players in several pathophysiologic modifications of the central nervous system. We used the spared nerve injury (SNI) of the sciatic nerve to induce glial maladaptive response in the ventral horn of lumbar spinal cord and examine its role in the remodeling of the tripartite synapse plasticity. Imaging the ventral horn revealed that SNI was associated with both an early microglial and astrocytic activation, assessed, respectively, by analysis of Iba1 and GFAP expression. Microglia, in particular, localized peculiarly surrounding the motor neurons somata. Perineuronal astrocytes, which play a key role in maintaining the homeostasis of neuronal circuitry, underwent a substantial phenotypic change following peripheral axotomy, producing reactive gliosis. The gliosis was associated with the reduction of glial aminoacid transporters (GLT1 and GlyT1) and increase of neuronal glutamate transporter EAAC1. Although the expression of GABAergic neuronal marker GAD65/67 showed no change, glutamate increase, as demonstrated by HPLC analysis, shifted the excitatory/inhibitory balance as showed by the net increase of the glutamate/GABA ratio. Moreover, endogenous NGF levels were altered in SNI animals and not restored by the intrathecal NGF administration. This treatment reverted phenotypic changes associated with reactive astrocytosis, but failed to modify microglia activation. These findings on one hand confirm the correlation between gliopathy and maladaptive plasticity of the spinal synaptic circuitry, on the other hand add new data concerning the complex peculiar behavior of different glial cells in neuronal degenerative processes, defining a special role of microglia in sustaining the inflammatory response.

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“…6 The rationale for this approach was based on previous reports from preclinical non-ocular neuropathic pain models on the use of neurotrophic factors, in particular nerve growth factor (NGF). 47,48 NGF reduced allodynia and hyperalgesia through reduction of reactive astrocytosis and glial modulation. Recovery of corneal nerve topography has been demonstrated with the use of AST in patients with NCP, 49 photoallodynia, 6 DED, 50 as well as with autologous plasma in patients with neurotrophic keratopathy.…”

Section: Management Of Patients With Neuropathic Corneal Painmentioning

confidence: 89%

Neuropathic Corneal Pain

2017

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Neuropathic pain is caused by a primary lesion or dysfunction of the nervous system and can occur in the cornea. However, neuropathic corneal pain (NCP) is currently an ill-defined disease. Patients with NCP are extremely challenging to manage and evidence-based clinical recommendations for the management of patients with NCP are scarce. The objectives of this review are to provide guidelines for diagnosis and treatment of patients with NCP and to summarize current evidence-based literature in this area. We performed a systematic literature search of all relevant publications between 1966 and 2017. Treatment recommendations are, in part, based on methodologically sound randomized controlled trials (RCTs), demonstrating superiority to placebo or relevant control treatments, and on the consistency of evidence, degree of efficacy, and safety. In addition, the recommendations include our own extensive experience in the management of these patients over the past decade. A comprehensive algorithm, based on clinical evaluation and complementary tests, is presented for diagnosis and subcategorization of patients with NCP. Recommended first-line topical treatments include neuro-regenerative and anti-inflammatory agents, whilst first-line systemic pharmacotherapy includes tricyclic antidepressants and the anticonvulsant. Second line oral treatments recommended include the opioid-antagonist and opiate analgesics. Complementary and alternative treatments, such as cardio-exercise, acupuncture, omega-3 fatty acid, and gluten-free diet, may have additional benefits, as do potential non-invasive and invasive procedures in recalcitrant cases. Medication selection should be tailored on an individual basis, considering side effects, comorbidities, and levels of peripheral and centralized pain. Nevertheless, there is an urgent need for long-term studies and RCTs assessing the efficacy of treatments for NCP.

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Intrathecal NGF Administration Reduces Reactive Astrocytosis and Changes Neurotrophin Receptors Expression Pattern in a Rat Model of Neuropathic Pain

Cited by 70 publications

References 42 publications

Autologous Serum Tears for Treatment of Photoallodynia in Patients with Corneal Neuropathy: Efficacy and Evaluation with In Vivo Confocal Microscopy

Autologous Serum Tears for Treatment of Photoallodynia in Patients with Corneal Neuropathy: Efficacy and Evaluation with In Vivo Confocal Microscopy

Astrocytes and Microglia-Mediated Immune Response in Maladaptive Plasticity is Differently Modulated by NGF in the Ventral Horn of the Spinal Cord Following Peripheral Nerve Injury

Neuropathic Corneal Pain

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