Upregulation of neuronal nitric oxide synthase in the periphery promotes pain hypersensitivity after peripheral nerve injury

Nerve Root Injections

Peripheral nerve injury often results in neuropathic pain that is manifested as hyperalgesia, and allodynia. Several studies suggest a functional role for neuronal nitric oxide synthase (nNOS) in the development or maintenance of neuropathic pain, but such a contribution remains unclear. In our current study, we found that intraplantar injection of the NOS substrate L-arginine or NO donor 3-morpholino-synonimine (SIN-1) produced mechanical hypersensitivity that lasted more than 24 h. Following L5 spinal nerve ligation (L5 SNL), immunoreactivity for nNOS in the ipsilateral L5 but not L4 dorsal root ganglion (DRG) was dramatically increased in mainly small- and medium-sized neurons and non-neuronal cells. L5 SNL caused increased nNOS immunoreactivity in the ipsilateral sciatic nerve, mainly in Schwann cells and the ipsilateral glabrous hind paw skin, mainly on the basement membrane. Furthermore, total nNOS protein and mRNA in the ipsilateral sciatic nerve and hind paw skin were markedly upregulated following nerve injury. Intraplantar injection of the NOS inhibitor 7-nitroindazole (7-NI) or the non-specific NOS inhibitor L-N(G)-nitro-arginine methyl ester (L-NAME) effectively suppressed SNL-induced mechanical allodynia. Collectively, these data suggest that in the periphery nNOS upregulation induced by peripheral nerve injury contributes to mechanical hypersensitivity during the maintenance phase of neuropathic pain. Blocking nNOS signaling in the periphery may thus be a novel therapeutic strategy for the treatment of neuropathic pain

Keywords : analogs & derivatives,Animals,Arginine,chemically induced,genetics,Hyperalgesia,injuries,Ligation,Male,metabolism,Molsidomine,Neuralgia,Neurons,Nitric Oxide Synthase Type I,Pain,Pain Threshold,Peripheral Nerve Injuries,pharmacology,physiology,physiopathology,Rats,Rats,Sprague-Dawley,Schwann Cells,Sciatic Nerve,Sensory Receptor Cells,Skin,Up-Regulation,, Neuronal,Nitric,Oxide,Synthase, work related upper limb disorder

Date of Publication : 2011 Sep 8

Authors : Kim KH;Kim JI;Han JA;Choe MA;Ahn JH;

Organisation : Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, South Korea

Journal of Publication : Neuroscience

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/21664432

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2021-06-03

I've just completed 3 months with Spine Central and set to continue. after using other Chiro's before I can't tell you how much of a level up this is. My overall health, posture and 'lack of back pain' have really opened me up to a better future. being a Dad of a young 3 year old, I can enjoy the time so much with my Boy. thank you Spine Central.

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2021-06-01

Mo Akmal & his team at The Spine unit were absolutely fantastic! My mother walked into the hospital in terrible pain & walked out a few hours later pain free ! She is 87 and now feels like 67 ! The attention she got was excellent I would highly recommend!

Miles McWilliams

2021-05-10

I have known Dr Akmal and his team for the past 8 years, I have seen him and his team ON and OFF for issues regarding my neck, C4/5, C5/6 , C6/7. I first had 3 lots of injections into this area back at the start of things. This helped me for 3 years. Dr Akmal did not want to operate at the time due to my age still been under 40 then. After 3 years I had to see Dr Akmal and his team again. We tried the injection route again but after a few attempts we then had to make the call to cut. I had C5/6 and C6/7 +/- C4/5 anterior cervical decompression and fusion / disc replacement carried out. This was a success and I was out of the hospital within 3 days and recovery took place for the next few months. This year I was operated on the back of my neck for a posterior cervical foraminotomy on the left side at the C5/6 and C6/7 levels. We tried the injections last year but this did not help. Due to Covid to this should have been carried out last year. Dr Akmal explained the risks include nerve injury, dural tear and pain post-operatively but the procedure is fairly routine and the risks are relatively low. Surgery has now taken place back in February. I was released the same day later that evening and been back for my check ups and things are looking up. I am currently training for a half triathlon that I will take part in second week of July. I am doing anything from 120 km to 170 km a week on the bike and running now upto 10 km a day on my running days. I have not been able to swim yet due to pools been closed but I have no issues with movement in me neck. I am very happy I chose Dr Akmal from the start. I did seen two others before him, they were happy to just cut and not look at what was best for me. I also strongly believe the newer technology Dr Akmal uses has really helped me any my life style I lead with sports. I know I would not have had the same results if I did not take the route with Dr Akmal. I really can’t say much more but I am very happy I met Dr Akmal when I did, he has been great and so has his team. Patient Miles McWilliams 😊

Saima Kash

2021-05-05

It was a fantastic experience for my mother in law right from the beginning when she had her first appt with Mr Akmal and was recommended to have a spinal surgery. He has been fantastic, extremely helpful and professional in helping her understand her own condition and pros and cons of the surgery and support her through out the whole process. I would highly recommend him for his excellent professional skills and experience in dealing with patients specially elderly patients.

Radu Ghebaru

2021-04-23

Quick and easy to book appointments (online and over the phone). Very helpful receptionist. I had a consultation with dr Akmal who is very professional , patient , kind and understanding. he explained me in details my problem. Trustful and confident in his job, I decided to follow his advice and treatment. I had yesterday a spinal injection . No sides effects so far. A bit in pain but it’s normal. I am aware that I will see the results in one week time only. Great team , exceptional staff (from the receptionist to the nurses and dr Akmal). I would recommend Harley Street Hospital - London Spine Unit to anyone who is having back pains.

Ashraf Elawad

2021-04-21

I had difficult times with my disc prolapse in my lower back. The pain was getting worse despite pain killers and physiotherapy. I was a bit nervous considering surgical treatment as a definte solution. The consultation with Mr. Mo Akmal was informative and reassuring and helped me to make a decision going ahead for the surgical option. On the day of the procedure, the staff was welcoming and looked experienced and knew exaclty what they were doing. Mr. Mo Akmal spoke to me before and after the procedure. In less than 2hrs, after the porcedure, I was able to stand, walk, and sit down with no pain. I strongly recommend Mr. Mo Akmal for anybody who has a similar condition.

Joe massimo

2021-04-16

I had minimally invasive spinal surgery for a Bulging disc at L5/S1 impinging on my S1 nerve root. Before surgery I couldn’t walk without a limp and would be in too much pain to walk further than a mile. Being only 21 years old and a keen athlete and student Osteopath, with an interest in sports rehabilitation, I wanted to get back to complete health and fitness from this injury. There is definitely a fear with spinal surgery that a lot of people have in the sports and therapy world however I knew I needed the operation to gain my leg function back and with Mr Mo Akmal and the team at the London spine Unit, I felt in great hands and they were very professional from start to finish with the process. They made me feel very comfortable and safe. I’d highly recommend Mr Mo Akmal and the Team at the London Spine Unit, they are very friendly and take great care of you. I’m feeling much better and am glad I chose to get the surgery done here.

Noam

2021-04-14

Very good treatment from Mr. Akmal and the staff with amazing results. After the first spinal injection I was sure the treatment won't work but as the team encouraged me to keep going to the second injection it then total disappeared. They were also very helpful with all the documents needed for the insurance cover. Much appreciated! I was struggling

Farzana

2021-04-07

In February 2021 I felt excoriating pain in my lower back. I was unable to stand up straight with my right leg having spasms occurring every hour. The sciatic pain accelerated within days I was bed bound to the point I needed help with basic daily activities such as making a cup of tea. I read the reviews about Dr Akmal, which I found beneficial and decided to book a consultation to see him. I was booked for a Consultation with Dr Akaml as well as an MRI scan & blood tests. I was pleasantly surprised to find out that I would get the results on the same day with the treatment options. Dr Akmal was very friendly he discussed the MRI scan with me that showed disc L4-L5 impinging the nerve, he suggested two options. One was the laser treatment to shrink the disc or the second the option was a discectomy. This would be a day procedure with no overnight stay. At no point did I feel pressured to decide on the procedures. Dr Akmal is incredibly knowledgeable this was evident through his years of experience with spinal procedures, I was 100% that the best option would be the discectomy and the best Surgeon was Dr Akmal. I was so impressed with the service and care that was offered at the clinic it was no less than first class to be honest, with no waiting time at all. On the day of the procedure I was in a private room, a lovely healthcare assistant was there to help me get into the hospital gown. Every staff member was ever so kind, they all made me feel at ease. Once I woke up I felt no sciatic pain at all which was an amazing feeling, an emotional moment to finally be rid of that burning sensation. Of course, there was some slight discomfort where the procedure had taken place. After surgery, I was able to stand on my two feet as well as being able to walk without any discomfort. Finally making my own cooked breakfast was a heavenly feeling! I can say with complete confidence that I trust Dr Akmal he is no doubt, on top of his field, a great human being who I’m so grateful to have met. If you want your life back I would highly recommend you book yourself in for a consultation with Dr Akmal, he is worth every single penny! Thank you Dr Akmal!

2021-04-05

Good treatment, uncomplciated, great solution,

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