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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  • edited May 2015
    http://onlinelibrary.wiley.com/doi/10.1002/ana.410360221/abstract;jsessionid=C74BB8149B72BC93A8FD3761323014EF.f03t03
    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. 

  • Day One: Some acute pain at the incision site and to the two fingers adjacent. This is different from normal incision pain I've experienced. Best described as a fuzzy pain maxing out at 5/10. No further findings.

    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.
  • Day Three: Pain has receded considerably. Median nerve is still palpable but only to the AC region. Sensitivity remains high at site. No exudate or noticeable inflammation. Healing appears to be occurring ridiculously quickly. More so than I've seen before.
  • So, this NGF. Does it promote the regrowth of only nerves that are damaged, or would it have an effect on a fully healed implant site as well? Although it's only been a little bit, I'm excited for the sensitivity you've already developed.
  • At this point, the incision line is strangely... difficult to find. The suture is out as of this morning. There is a place that still has a touch of dried blood/crust from the initial insertion. I'm being appropriately cautious about not picking or traumatizing the area. Pictures will be posted.
  • edited May 2015
    Kawamoto K, Matsuda H (2004). "Nerve growth factor and wound healing". Prog. Brain Res. 146: 369–84. doi:10.1016/S0079-6123(03)46023-8. PMID 14699974.
    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.
  • Next question:  When can we buy magnets coated with this stuff?
  • I can do that. It's costly though.
  • I'm afraid it would be like 100$, just to start feeling the magnetic fields faster (I only found this site selling them thought so I dont know how cheap you can get them http://www.biotrend.com/com/shop?itemid=C-45034-5 ), its fine for testing but I'm afraid until you can produce it cheaper it wont be worth it.
  • So if someone could harvest platypus venom... /joke
  • Australia, we're looking at you...
  • The platypus has the brain of a dolphin.
  • So ask it for some venom. We harvest milk and cows have the brain of... a cow....

  • I don't know if y'all realize what harvesting platypus venom entails (I can explain later). But, if someone in australia is a specialist in harvesting platypus venom, Have at it!
  • Pain receded throughout the first week with no ensuing inflammation. As of today, 1 full week out, the pain has returned at a rather acute level near the incision site and throughout the entire finger upon which the procedure was performed. The incision is totally closed, but became more visually apparent over time. There is darkening of the skin beneath the incision site. Sensitivity is very high - greater than in older magnets I have. Im continuing to ice and use ibuprofen.
  • Would NGF have any effect if injected long after recovery? Like to increase sensitivity of old implants?
  • Yes, I believe it will. That's amongst the next rung of tests.
  • So on a scale from negligibly to  a fucking lot, how much more painful has his implant been, compared to a non-NGF one?
  • Id say 5/10
  • Because of the pain I'm wondering if the post injection rather than coated magnet would be more ideal. That way pain from healing will be gone and then you'd only have the tingle of growing nerves?
  • There would still be pain. But I agree. A post-healing injection would be preferable if it yielded the same results. You can keel over in pain without fearing rejection.
  • edited May 2015
    I disagree. In my opinion the role NGF plays in promoting wound healing makes it valuable for immediate injection, as this (for me) outweighs any temporary pain one might feel post-implant.
  • I think it depends on the degree of healing acceleration, as well as any potential rejection issues.
  • Personally I'd use something else for the actual healing promotion and save this for increasing nerve content if at all possible.
  • Could this be used to make magnet implants in, like, your arm, feel as sensitive as in your fingers?
  • If it could that would make for some interesting new locations. Do a line of them down your arm and start getting full body fields

  • If the NGF pans out for off-finger locations, I totally want to install a few magnets around my body for a full sensory array...Something like one on each upper and lower arm/leg, one near the collarbone on each side, one below each of the nipples/pecs, 4 in a ring around the midriff. Assuming, of course, that the NGF has enough effect to be worth pursuing, otherwise these locations wouldn't feel diddly squat.
  • Oh and there's the added benefit of discouraging you from screwing around with your new implants right after implantation.

    I wonder whether it would be of any use in those tragal magnet implants for the invisible headphones.
  • Cass actually did some implants in the general region of the occipatal bone region on a local (read LA) grinder. Im sure that she will post some info soon *stern look at people who should participate*. We are, of course, super stoked about the initial ngf and so many more needle stabs will be happening soon.
  • Maybe using a jet-injector (Link) would improve the effects when used post-implantation. The injection dynamics seem like they'd be beneficial, since the NGF is dispersed into a cone, instead of being concentrated into a single location which then needs to be dispersed.
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