Dorsal Root Ganglion Block

Schwann cell p75NTR prevents spontaneous sensory reinnervation of the adult spinal cord

Schwann cells are attractive candidates for repair of the injured spinal cord. Transplanted Schwann cells are permissive to regeneration, but their ability to promote regeneration into distal spinal cord remains weak despite their production of growth-promoting neurotrophins. Schwann cell activation such as that which accompanies peripheral nerve injury results in massive upregulation of the p75(NTR) pan-neurotrophin-receptor. Here we test the hypothesis that this p75(NTR) upregulation following dorsal root injury limits availability of endogenous neurotrophin to axons and restricts regeneration of injured axons into the spinal cord. We injured dorsal roots (fourth cervical to second thoracic) in mice lacking the neurotrophin-binding domain of p75(NTR) and in wild-type littermates. Axonal regeneration was assessed by selective tracing of neurotrophin-responsive and non-responsive dorsal root ganglion neurons. Functional reinnervation of the spinal cord was assessed in behavioural experiments and via Fos immunohistochemistry following formalin injection into the forepaw. We also measured levels of nerve growth factor and neurotrophin-3 following nerve injury in knockout and wild-type mice, and used Trk-Fc receptor chimeras to block nerve growth factor and neurotrophin-3 signalling in dorsal root ganglion/Schwann cell co-cultures and following dorsal root injury in vivo. The roles of neuronal and glial p75(NTR) were assessed in transplant experiments in vivo and in co-cultures. We found that nerve growth factor and neurotrophin-3-responsive axons regenerated into the spinal cord of p75(NTR) knockout mice where they made functional connections with dorsal horn neurons. Despite equivalent levels of nerve growth factor and neurotrophin-3 in wild-type and knockout mice, successful regeneration in knockouts was neurotrophin-dependent. Transplantation of p75(-/-) neurons into a wild-type environment, p75(-/-) peripheral nerve grafts into the injured p75(+/+) spinal cord, and dissociated sensory neuron/Schwann cell co-cultures showed that the absence of p75(NTR) from glia, not from neurons, promotes regeneration. These findings indicate that Schwann cell p75(NTR) restricts neurotrophin availability to the extent that it prevents spontaneous sensory axon regeneration into the spinal cord. The implication is that inactivating p75(NTR) in Schwann (or olfactory ensheathing) cells may enable axons to grow beyond transplants, improving the outcome of spinal cord injury

Keywords : Adult,Age Factors,Animals,antagonists & inhibitors,Axons,Cells,Cultured,Coculture Techniques,deficiency,genetics,Growth,Immunohistochemistry,injuries,Male,Mice,Mice,Inbred C57BL,Mice,Knockout,Nerve Growth Factor,Nerve Growth Factors,Nerve Regeneration,Neural Inhibition,Neurons,Neurotrophin 3,Peripheral Nerve Injuries,physiology,Rats,Rats,Sprague-Dawley,Receptors,Nerve Growth Factor,Regeneration,Schwann Cells,Sensory Receptor Cells,Spinal Cord,Spinal Cord Injuries,transplantation,ultrastructure,, Cell,P75ntr,Prevents,Spontaneous,Sensory, neck pain computer chair

Date of Publication : 2010 Feb

Authors : Scott AL;Ramer MS;

Organisation : Blusson Spinal Cord Centre, , Vancouver, BC V5Z 1M9, Canada

Journal of Publication : Brain

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/20047901

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2022-06-08

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2022-06-06

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Extraordinary Care My 81 year old mother who has retired in Ghana was suffering from severe lower back pain so a local surgeon put her through discectomy with hardware (spine screws). The procedure was essentially botched, with one screw breaching her spinal canal resulting in extreme pain; unable to walk, pins and needles and numbness in the left leg. The hardware subsequently had become infected and loosened as a result. Her life after this surgery was the worse she has ever experienced in all her life. She had no doubt that she was eventually to die from the infection and pain. Fortunately, through diligent search, we found Mr Akmal and his team at The UK Spine Centre. She had a zoom consultation and with a ready MRI and CT scan, Mr Akmal knew exactly how to have her back to fitness and a better quality of life. She travelled to England on 26 March 2022 and had the surgery on 11 April 2022. It was a day-case. It lasted no more than 1 hour 30 minutes. She was on my feet within 2 hours pain free - still pain free 5 weeks on! To her this is simply a miracle ! She is grateful to Jehovah God for Mr Akmal and his team - thoroughly professional bunch at the top of their game. No one deserves to suffer the pain she experienced for two years. She seriously recommends Mr Akmal and his team for anything SPINE!

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2022-05-18

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2022-04-22

I had a massive bulging disk on my back… I had a massive bulging disk on my back compressing my nerve for three years. It caused me excruciating pain and almost left me disabled. I was on both crutches and completely homebound due to the severity of pain and mobility limitations. I had my lumber surgery two weeks ago and walked out of hospital within a few hours pain free on my right leg that was almost paralysing prior to surgery. The disk was shaved off releasing the nerve completely. Two days after surgery I had excruciating pain on my head that is unexplained as I had CT scan and MRI which were all fine. Dr Akmal has suggested it could be from the anaesthetic. I am extremely grateful to Dr Akmal and his very welcoming and cari g team. I would highly recommend his clinic as I have had excellent recovery.

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2022-04-02

Thank you Mr Aklam After having a poor and very slow experiance in glasgow . I contacted Mr mo Amlam . Who is a true gentleman, great listener and paitent . We transfered my scans and treatments from glasgow to harley street . Mr Aklams p.a arranged a quick zoom to start our contact .I then went down for a meeting and examination and what should have been a spec scan .only to be told of a UK shortage . So 4 weeks later the scan took place in wellington hospital . Before I traveled back to glasgow. 5 days later I got a call to book me in to 19 harley street for a l3 and l4 debridement and stabilisation. The opp took place on 24th March. 2hours I was out walking 4 hours later . My pain in back groin and foot was all gone .thanks to Mr aklam . Top of his craft but more importantly pouts his patients first .he really wants to help you get better. Thank you so much Mr Robert harvey

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2022-03-22

Amazing service and an amazing treatment! I can't thank Mr Akmal and team at the London Spine Unit enough for their help. I had a herniated disc in my back which was causing pain and restrictions. Compared to other offers of surgery (e.g. several nights in hospital), the day surgery and minimally invasive procedure were hugely appealing. I am now 3 weeks post surgery, have no pain and am recovering incredibly quickly if I compare myself to friends who have had a similar procedure. it was truly remarkable, straightforward and the team were kind, friendly and always helpful. very highly recommended!

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2022-03-17

Great service and painless procedure Great service and painless procedure. Definitely alleviated the pain

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