Joo-Yeon Kang, Dae Young Yoo, Kwon-Young Lee, Wooseok Im, Manho Kim, Jung Hoon Choi, Hwa-Young Youn, Sae Hoon Kim, In Koo Hwang, Jin-Young Chung, Kang, Joo-Yeon, Yoo, Dae Young, Lee, Kwon-Young, Im, Wooseok, Kim, Manho, Choi, Jung Hoon, Youn, Hwa-Young, Kim, Sae Hoon, Hwang, In Koo, and Chung, Jin-Young
Background: Nerve 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.Results: Vehicle 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.Conclusions: Given 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. [ABSTRACT FROM AUTHOR]