Nerve Growth Factor for proliferation of sensory neurons
5/2/15 M31s were implanted into the Ring fingers of both Glims and cassox via scalpel method. Glims is serving as control and recieved no Nerve Growth Factor (NGF) of any form.
The M31 implanted into cassox (sorry 3rd person from now on out of conformity) after administration of 5 ug of Beta- NGF dissolved 0.5 ml 0.9% solution of NaCl directly into the incision site. An additional 5 ug of B-NGF in solution was injected subcutaneously 5 mm proximal to the incision site. We hypothesize that the NGF will facilitate quicker neuron growth/regrowth, quicker time to sensitivity, and a chronic/long term increase in sensitivity/effect provided by the implanted magnet. Initial injection was painless but resulted in a "fuzzy" feeling in the hand. Throughout the initial 12 hours following administration pain progressed to 3-4/10 throughout the effected digit as well as to the fingers to either side. Pain was distinct from incision pain. No acute swelling or reactions noted. Vitals remained stable and within normal limit.
Narrative - ( Still haven't found that perfect balance of writing research and writing for readers) So NGF is a family of proteins associated with growth, maintenance and neuron proliferation. There's been quite a bit of research regarding it. I'll post some of it below. One example of NGF dysnfunction is found in a condition called HSAN5 which results from a mutation in the gene which codes for NGF. Children born with HSAN5 are unable to sense pain which often results in self-mutilation, for example eating through their own lips and cheeks.
NGF is also found in the venom of male duck billed platypus. Its neither necrotic nor neurotoxic,but platypus venom is described as being painful enough that people killed themselves to end the pain. The NGF in the venom causes the local sensory neurons and the sensory pathways to the brain to be "reinforced" (this is a colloqual/short hand way of describing some research indicating increased axonogenesis and nerve proliferation etc. If this description doesn
t do it fer ya, please read the included reference reasearch). Research has shown that people are significantly more sensitive to painful stimuli. Other sensory modalities appeart to also be postively effected such as the sensation of pressure, while others such as the sense of vibration is not.
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94, DR. Petty et. all
This phase I double-masked, randomized, placebocontrolled study evaluated the safety of single intravenous or subcutaneous doses of recombinant human nerve growth factor (rhNGF) in healthy human volunteers at doses ranging from 0.03 to 1 μg/kg. No life-threatening adverse events were seen at any dose. At doses above 0.1 μg/kg, subjects reported mild to moderate muscle pain, primarily in the bulbar and truncal musculature. The duration and severity of these myalgias varied in a dosedependent manner, and women appeared to be more susceptible than men. Intravenous rhNGF produced earlier and more pronounced systemic effects than did identical subcutaneous doses. Subjects receiving subcutaneous rhNGF noted hyperalgesia at the injection site, a local effect persisting up to 7 weeks, that also varied in a dose-dependent manner. Antibodies to NGF were not detected in any subject. These results indicate that systemically administered rhNGF exerts a characteristic and reproducible biological effect in healthy subjects at very low doses and in a dose-dependent manner.
http://www.uniprot.org/uniprot/P01138
UniProt – This site provides comprehensive sequencing and protein function information. Per Uniprot, BNGF functions are maintenance and development of sympathetic and sensory neurons. BNGF binds to NTRK1 and NGFR receptors activating Tyrosine Kinase. Many neurons undergo apoptosis in the absence of NGF. NGF is elevated during an inflammatory response. Functions include: Positive regulation of stem cell proliferation, Influences memory formation,Peripheral nervous system development and axogenesis. BNGF is involved in the perception of pain. BNGF is produced in the Golgi Lumen. Variations in the BNGF system causes HSAN5 – a genetic condition resulting in the inability to feel pain.
http://www.sciencedirect.com/science/article/pii/S0304395903000125
A double-blind, placebo controlled study that tested the effects of 5ug of NGF administered intramuscularly into the Masseter muscles of healthy subjects. This study showed a decrease in pain tolerance (via pressure pain threshold reported on a scale of 0-10) for 7 days. This study shows that NGF administration can result in hyperalgesia and Allodynia for 7 days after administration.
http://www.jneurosci.org/content/11/9/2914.short
Delayed Neuronal Death normally develops several days after a global ischemic event. Administration of NGF significantly reduced DND. This shows NGF is neuroprotective.
Intradermal recombinant human nerve growth factor induces pressure allodynia and lowered heat-pain threshold in humans. AB Nerve growth factor (NGF) plays a biologic role in the development and maintenance of sympathetic and small sensory neurons. Because it facilitates nerve fiber regeneration, lowers heat-pain threshold (hyperalgesia), and prevents or improves nerve dysfunction in experimental neuropathy, it is being considered as a putative treatment for certain human polyneuropathies. In 16 healthy subjects, we tested whether intradermal injection of minute doses of recombinant human NGF (1 or 3 micrograms) compared with saline induces hyperalgesia or alters cutaneous sensation (at the site of injection) as measured by symptom scores, clinical examination, or quantitative sensory testing with Computer Assisted Sensory Examination (CASE IV). Most subjects had, as their only symptom, localized tenderness of the NGF-injected site and only when the site was bumped or compressed. Slight discomfort developed in volar wrist structures (with flexion of fingers) or tenderness of deep structures to palpation over the bicipital groove or supraclavicular region. The Neuropathy Symptoms and Change questionnaire indicated that pressure allodynia was significantly localized to the NGF-injected side from 3 hours to 21 days after injections. Light stroking of the skin did not induce tactile allodynia. Compression of injected sites induced pressure allodynia that occurred more frequently and significantly on the NGF-injected side after 3 hours and was maintained for several weeks. No abnormality of vibratory or cooling detection threshold developed from NGF injection. By contrast, heat-pain threshold (HP 0.5, p = 0.003) and an intermediate level of heat-pain (HP 5.0, p < 0.001) were significantly lowered 1, 3, and 7 days (and in some cases at 3 hours and 14 and 21 days) after NGF injection. The time course of pressure allodynia and heat-pain hyperalgesia is too rapid to be explained by uptake of NGF by nociception terminals, retrograde transport, and upregulation of pain modulators. Local tissue mechanisms appear to be implicated. It remains to be tested whether recombinant human NGF prevents, stabilizes, or ameliorates small fiber human neuropathies.
Recombinant human nerve growth factor (rhNGF-[beta]) gene transfer promotes regeneration of crush-injured mental nerve in rats. AB Objective: The aim of this study was to evaluate whether the recombinant human nerve growth factor (rhNGF-[beta]) gene transfer at a crush-injured sensory nerve can enhance nerve regeneration. Study Design: A 4-mm crush injury was made on the mental nerve of mandible in rats, and rhNGF-[beta] adenovirus (6 [mu]L, concentration = 1.0 x 1011 pfu/[mu]L) was injected at the crushed site for the experimental group (NGF-Ad group, n = 15) and the same volume of PBS for the controls (PBS group, n = 15). A sham group of uninjured nerve was also used for the normal control (Sham group, n = 15). The effect of rhNGF-[beta] adenovirus injection was evaluated by real-time reverse trascriptase polymerase chain reaction for the quantification of nerve growth factor (NGF), low-affinity NGF receptor (p75NTR), and its tyrosine receptor kinase A (trkA) mRNA expression at the trigeminal ganglion (TG) 5 days after injection. Nerve regeneration was evaluated with sensory test, retrograde axonal transport in the TG, and histomorphometric study for 4 weeks. Results: NGF, p75NTR, and trkA mRNA expression was significantly increased at the TG 5 days after injection of rhNGF-[beta] adenovirus (P < .05). The NGF-Ad group showed improved sensory recovery (P < .05), and the number of retrograde-labeled sensory neurons and soma size of TG were larger compared with the PBS groups (P < .05). Histomorphometrically, the myelinated axon number, myelin thickness, and G-ratio in the NGF-Ad group was also significantly higher than the PBS groups (P < .05). Conclusions: Recombinant human nerve growth factor gene transfer promoted regeneration of crush-injured mental nerve.
Sources:
http://www.sydlabs.com/beta-ngf-protein-p8159.htm (98.00 for 10 ug)
http://www.biosensis.com/human-beta-nerve-growth-factor-protein-expressed-mammalian-cells-p-901.html (127.00 for 2 ug)
Day Two: Pictures taken during dressing change. Wound is closed with no exudate or s/s of inflammation. Pain has increased to 6/10 upon palpation. Pain is clearly palpable along the entire length of the Median Nerve. Pain begins on the dorsal surface of hand at digit 3 and spreads proximally to the midpoint of the posterior antebrachial. At that point this line of pain wrap around the ventral arm/antecubital region. This painful line can then be felt all the way up to the axilla. This is the path of the median nerve. Pain can be felt at rest and is increased upon pressure or palpation.
Playing with the magnet vs. other prior magnet implant, the sensitivity is clearly higher. This new implant provides sensation long before the other implants do. I'm really hoping the arm pain goes away soon though.
So apparently another effect of NGF is an increase in the rate of wound healing. If you don't die in the next month we should make this an n=2 study when I come up in June. Might have to do a different finger though I seem to have a significant amount of scar tissue.