SP, CGRP changes in pyridoxine induced neuropathic dogs with nerve growth factor gene therapy

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.

The R18 Polyarginine Peptide Is More Effective Than the TAT-NR2B9c (NA-1) Peptide When Administered 60 Minutes after Permanent Middle Cerebral Artery Occlusion in the Rat

“…Taken together, the results from the current study support other findings from our laboratory [ 8 – 10 ] and suggest that polyarginine and arginine-rich peptides may represent a new class of neuroprotective agents with enormous clinical potential for the treatment of acute and chronic neurological injuries. Importantly, it is possible that the reported beneficial effects of arginine-rich cell penetrating peptides fused to a “neuroprotective peptide” in animal studies of acute brain injury are largely attributable to the effects of the arginine residues contained within the peptide [ 9 ].…”

“…The results of the present study add to our previous findings, which showed that 1000 nmol/kg R18 when administered 30 minutes after permanent MCAO significantly reduces infarct volume in the rat [ 10 ]. Importantly, we now show that R18 is effective over an even wider therapeutic window (60 min) and broader dose range (100–1000 nmol/kg) and that, on balance, R18 is more effective than the extensively characterised neuroprotective peptide, TAT-NR2B9c.…”

“…The filament permanent MCAO stroke model as performed in our laboratory has been described previously [ 10 , 16 ]. Briefly, male Sprague-Dawley rats weighing 275–340 g that had been fasted overnight underwent facemask anesthesia with 4% of isoflurane (mix 30% oxygen/70% nitrous oxide) and maintenance with 2% isoflurane.…”

“…In terms of neuroprotective agents, our laboratory has recently demonstrated that polyarginine and arginine-rich peptides have potent neuroprotective properties in in vitro injury models that mimic the effects of stroke [ 7 – 9 ]. Moreover, we have extended these in vitro findings by demonstrating that the polyarginine peptides R9, R12, and R18 significantly reduce infarct volume in a permanent middle cerebral artery occlusion (MCAO) stroke model [ 8 , 10 ]. Based on these in vitro and in vivo findings, we have recently proposed [ 8 , 9 ] that arginine-rich peptides including “neuroprotective peptides” fused to arginine-rich cell penetrating peptides (e.g., TAT-NR2B9c [ 11 ] and TAT-JNKI-1 [ 12 ]) represent a new class of neuroprotective agents for which arginine residues are critical for neuroprotection.…”

Sonic hedgehog signaling pathway promotes pancreatic cancer pain via nerve growth factor

“…PNI extending into the extrapancreatic nerve plexus is a histopathological characteristic of PC and leads to abdominal pain 6. NGF induces thermal and mechanical sensitization of neurons, and the recent use of NGF-sequestering antibodies attests to the ongoing role of this neurotrophin in chronic pain 23 24. However, the specific mechanism contributing to PC pain is unclear.…”