Abstract
BackgroundNerve growth factor (NGF) is known not only as a major factor for neuronal plasticity but also as a pain stimulator. Although there have been several trials with NGF for its application in the regeneration or protection of the nervous system, the pain induced by NGF remains a challenge to be overcome. In this study, the pain induced by NGF gene therapy was evaluated.ResultsVehicle or recombinant dog NGF plasmid was administered into the intrathecal space of dogs. Twenty-four hours after the vehicle or NGF plasmid inoculation, dogs were subcutaneously treated with 150 mg/kg pyridoxine every day for 7 days. For pain assessment, physical examination and electrophysiological recording were performed. Only in the vehicle-treated group, weight loss occurred, while NGF plasmid inoculation significantly improved this physical abnormalities. In the vehicle-treated group, electrophysiological recordings showed that H-reflex disappeared at 24 h after the last pyridoxine treatment. However, in the NGF plasmid inoculated group, the H-reflex were normal. In the results of immunohistochemistry, the NGF plasmid administration efficiently expressed in the dorsal root ganglia and significantly increased the pyridoxine-induced reduction of calcitonin gene-related peptide (CGRP) immunoreactive neurons, but not in substance P immunoreactive neurons, in the dorsal root ganglia.ConclusionsGiven these results, we reason that NGF gene therapy in pyridoxine induced neuropathic dogs does not induce neuropathic pain with this dosage, even with increasing the expression of CGRP.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-015-0236-5) contains supplementary material, which is available to authorized users.
Highlights
Nerve growth factor (NGF) is known as a major factor for neuronal plasticity and as a pain stimulator
It has been demonstrated that dose-dependent hyperalgesia is present at the injection site after a recombinant human NGF subcutaneous injection for peripheral neuropathies [8], there were no observable side effects when small amounts of NGF were injected through an intra-cerebro-ventricular channel for central nervous system diseases [12]
The H-reflexes in the NGF therapy group slightly decreased after pyridoxine injection, but significant differences were not detected before or after the pyridoxine injection (p > 0.05) (Fig. 3)
Summary
Nerve growth factor (NGF) is known as a major factor for neuronal plasticity and as a pain stimulator. It has been demonstrated that dose-dependent hyperalgesia is present at the injection site after a recombinant human NGF subcutaneous injection for peripheral neuropathies [8], there were no observable side effects when small amounts of NGF were injected through an intra-cerebro-ventricular channel for central nervous system diseases [12]. When injections of large amounts of NGF were administered, weight loss or back pain was reported even though it was administrated intra-cerebro-ventricularly [13]. Based on these results, we could understand that the route of injection and the amount of NGF being injected are important factors for the occurrence of neuropathic pain
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