Role of PAF receptor in proinflammatory cytokine expression in the dorsal root ganglion and tactile allodynia in a rodent model of neuropathic pain

Nerve Root Injections

BACKGROUND: Neuropathic pain is a highly debilitating chronic pain following damage to peripheral sensory neurons and is often resistant to all treatments currently available, including opioids. We have previously shown that peripheral nerve injury induces activation of cytosolic phospholipase A(2) (cPLA(2)) in injured dorsal root ganglion (DRG) neurons that contribute to tactile allodynia, a hallmark of neuropathic pain. However, lipid mediators downstream of cPLA(2) activation to produce tactile allodynia remain to be determined. PRINCIPAL FINDINGS: Here we provide evidence that platelet-activating factor (PAF) is a potential candidate. Pharmacological blockade of PAF receptors (PAFRs) reduced the development and expression of tactile allodynia following nerve injury. The expression of PAFR mRNA was increased in the DRG ipsilateral to nerve injury, which was seen mainly in macrophages. Furthermore, mice lacking PAFRs showed a reduction of nerve injury-induced tactile allodynia and, interestingly, a marked suppression of upregulation of tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) expression in the injured DRG, crucial proinflammatory cytokines involved in pain hypersensitivity. Conversely, a single injection of PAF near the DRG of naive rats caused a decrease in the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner and an increase in the expression of mRNAs for TNFalpha and IL-1beta, both of which were inhibited by pretreatment with a PAFR antagonist. CONCLUSIONS: Our results indicate that the PAF/PAFR system has an important role in production of TNFalpha and IL-1beta in the DRG and tactile allodynia following peripheral nerve injury and suggest that blocking PAFRs may be a viable therapeutic strategy for treating neuropathic pain

Keywords : 1-Acylglycerol-3-Phosphate O-Acyltransferase,Animals,antagonists & inhibitors,Cyclooxygenase Inhibitors,Cytokines,deficiency,Disease Models,Animal,drug effects,enzymology,Ganglia,Spinal,genetics,Glycoproteins,Inflammation,Inflammation Mediators,Injections,injuries,Interleukin-1beta,Lipoxygenase Inhibitors,Macrophages,Membrane Glycoproteins,metabolism,Mice,Models,Biological,Neurons,Pain,pathology,Peripheral Nerve Injuries,Peripheral Nerves,pharmacology,Platelet Activating Factor,Platelet Membrane Glycoproteins,Rats,Receptors,G-Protein-Coupled,Receptors,Lysophosphatidic Acid,Touch,Tumor Necrosis Factor-alpha,Up-Regulation,, Paf,Receptor,Proinflammatory, spine health uk

Date of Publication : 2010 May 3

Authors : Hasegawa S;Kohro Y;Shiratori M;Ishii S;Shimizu T;Tsuda M;Inoue K;

Organisation : Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

Journal of Publication : PLoS One

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/20454616

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2021-06-03

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2021-06-01

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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 😊

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2021-05-05

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2021-04-23

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2021-04-21

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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.

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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

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Role of PAF receptor in proinflammatory cytokine expression in the dorsal root ganglion and tactile allodynia in a rodent model of neuropathic pain | Hypogastric region pain