Category Archives: Lumbar Radicular Pain Including Severe Sciatica

A SINGLE Perispinal Etanercept Injection by Edward Tobinick MD for Severe Nerve Pain including Sciatica and Post-Stroke Pain (2/2)

Feature Image sourced from:

https://seekingalpha.com/article/3956875-invivos-therapy-verge-becoming-de-facto-treatment-spinal-cord-injury

 

Dear Pain Matters blog readers,

Introduction

Infliximab, Etanercept and other selective anti-TNF drugs are sometimes used to treat:

  • Lumbar radicular pain;
  • Sciatica;
  • Post-stroke pain;
  • Complex regional pain syndrome (CRPS);
  • Rheumatoid arthritis;
  • Crohn’s disease; and
  • Other painful conditions.

This blog post explores the pain-relieving effects of a single perispinal Etanercept injection in certain patients with sciatica, post-stroke pain and other severe nerve pain.

An earlier blog post discussed anti-TNF drugs (Infliximab) for CRPS:

Anti-TNF Drug (Infliximab) Therapy for CRPS and Other Chronic Pain Conditions (1/2)

A Single Perispinal Etanercept Injection for Pain in Back (Sciatica), Neck and after Stroke – 9 Patient Stories

A handful of pain patient stories (N=9) were selected from the Institute of Neurological Recovery’s (INR’s) website (that has over 300 patient videos).  This website also includes media stories, a blog and countless scientific publications by Dr Tobinick and his peers (see References).

https://www.nrimed.com

Please note the following disclaimer quoted from Dr Tobinick’s Patient YouTubes: 

‘Disclaimer: Individual results vary, not all patients respond. Additional doses may be necessary to maintain the clinical response. Treatment for these indications is innovative (“off-label”). The method of off-label treatment utilized is a patented invention of the INR®.’

 

(1) Kerry and Her Single Perispinal Etanercept Injection for Severe Leg and Back Pain

‘Kerry’ (not her real name) had intense right ankle, leg and back pain including burning pain for 6 months nonstop.  She walked very slowly with an abnormal gait to prevent the pain from shooting down her leg.  Her sleep was severely compromised.

Kerry was offered a single dose of perispinal Etanercept by Dr Tobinick at the Institute of Neurological Recovery, Florida, on 11 September 2009.

Kerry was immediately pain free at rest!  When her right leg was gently lifted, there was only a little pain. She said that this was likely due to not doing enough stretching exercises.   Kerry did not have pain in her buttocks nor lower back and her gait was vastly improved.

In Kerry’s words, ‘I feel good!  Thank you.  Yeah, I feel good.’

At her follow-up 2 weeks later on 25/9/2009, Kerry said that she felt excellent.  She slept well and was able to do all her normal activities.

Kerry attributed her complete recovery from pain and mobility to her single dose of Etanercept.

For more details, please view Immediate and sustained relief from severe pain (a 4-minute YouTube dated 25/11/2009 by the Institute of Neurological Recovery, Florida).

https://www.youtube.com/watch?v=Np62fRdIo1E

 

(2) Ana and Her Single Perispinal Etanercept Injection for Severe Back and Leg Pain

‘Ana’ (not her real name), a woman with a warm Spanish accent, suffered constant severe back and leg pain for 2 years.

Ana’s unrelenting pain affected her mobility and sleep.  Her husband had to help put on her shoes and underwear.  Ana tried different pain medications including Tramadol, Vicodinand Naproxen without success.  Ultimately,Ana lost her job because of her ongoing pain.

Ana booked an appointment with Dr Tobinick at the Institute of Neurological Recovery, Florida, on 4 May 2009. While seated during the examination, Ana’s left leg was gently raised.  This resulted in increased pain in her back that spread down her left leg. It was impossible to lift her other leg due to excruciating pain.

Thereafter, Ana received a single dose of perispinal Etanercept.  Three minutes afterward, Dr Tobinick stated,

‘All right now. … The dose was at 9 minutes after 4, and this … is 3 minutes [later].  What is happening?’

Ana said, ‘I can move my legs!  [She laughs, with tears of joy in her eyes.]  Oh God! Oh God!’

Dr Tobinick asked, ‘Is this different?’

‘Oh yeah!’, she exclaimed.

He continued, ‘When was the last time you felt like this?’

Ana replied, ‘I don’t know, about 2 or 3 years ago.  Oh my God! … I can’t believe this!  Two years of pain … Oh my God!  Wow!  You’ve given my life back!

Dr Tobinick asked, ‘What do you think?’

She tearfully said, ‘Thank you!’

Dr Tobinick continued,

‘How do your legs feel? … Before, it was hurting.’

She happily replied, ‘Oh, thank you … I have legs!’

He added, ‘Can you walk?’

She said, ‘Oh my God!’

Dr Tobinick said, ‘How do you feel?  Let’s go down the hall.’

Ana said, ‘Oh my God! … This is incredible!  Oh God.’

He asked, ‘Did it work?’

She enthusiastically replied, ‘Yes!! … Thank you so much!’

Ana (and her husband) had a follow-up visit with Dr Tobinick a week later on 11 May 2009.

Ana’s husband exclaimed,

‘… This is another person.  That was not her … I got her back! … The smile! … She’s alive! … She’s getting back into the game … She’s moving!’

Ana had another follow-up visit with Dr Tobinick 3 months later on 14 August 2009.

Dr Tobinick asked,

‘What kind of difference has this [single dose of perispinal Etanercept] made for your life?’

Ana replied, ‘Tremendous! … I’m holding my grandson and playing with him … I can have him in my lap and play with him. … And enjoy it!  I wasn’t able to do that before!  I’m doing a lot better!’

Dr Tobinick said, ‘Wonderful!’

‘Thank you, Dr Tobinick!’

‘You’re welcome!’

For more details, please view Immediate relief of 2 years of constant back pain and sciatica (an 8-minute YouTube dated 25/11/2009 by the Institute of Neurological Recovery, Florida).

https://www.youtube.com/watch?v=vP6Nw1_OGIg

 

(3) Brenda’s Single Perispinal Etanercept Injection Brings Fast Relief from Severe Sciatica

A young woman named ‘Brenda’ (not her real name) had a slipped disc in her 4th vertebra and severe sciatic pain for 5 months since December 2008.  Her gait was affected and she had severe pain from the right side of her lower back and buttocks that spread down both legs.  There was unbearable pain in her right leg down to her toes and less pain in her left leg.

Brenda was given Vicodin, steroids and morphine injections for her pain, to no avail.  When she was rushed to hospital for severe back pain (several times), the neurosurgeon told her that she needed emergency back surgery.

When Brenda went to see Dr Tobinick on 21 April 2009, he confirmed that the pain on the right side of Brenda’s back worsened when her left leg was lifted.  Thereafter, Brenda was offered a single dose of perispinal Etanercept.

Within only 1 minute after her injection, Brenda’s knee no longer hurt!  There was no pain in her back even as she lifted both legs.  When she stood up to walk around, there was nil pain and her gait was normal.

Happy to finally be pain free, she started dancing!

When asked by Dr Tobinick, ‘How much pain do you have?’

She replied, ‘I don’t have any pain!’

He confirmed, ‘Your pain is all gone?’

She answered cheerfully,

‘I’m not in pain!  Nope, I’m not in pain!  Nope! I’m good!  Before, I couldn’t stand on this leg … I feel good!  I feel great!’

For more details, please view Rapid relief after 5 months of severe sciatic pain (a 5-minute YouTube dated 7 Jan 2016 by the Institute of Neurological Recovery, Florida).

https://youtu.be/2K5yLrJSq0A

https://www.nrimed.com/videos-by-category/back-neck-pain/

 

(4) Tim’s Single Perispinal Etanercept Injection Offers Relief from Sciatica in Minutes

‘Tim’ (not his real name) went to see Dr Tobinick on 4 April 2007 for severe sciatica.  The intense pain was constant and unbearable for 3 weeks and affected his work, quality of life and sleep.  He had pain in his back and buttocks that extended down his left leg to his calf.

In Tim’s words, ‘It feels like somebody took a baseball bat and hit my leg.’

The pain increased in Tim’s left (not right) leg when Dr Tobinickgently moved his right leg.  Tim’s pain was more intense when seated and it lessened when he stood up.  He was able to walk ‘with a slight limp but real slow … real gently’.

Tim had pain relief within a 1 minute after Dr Tobinickinjected Etanercept perispinally.  

In response to Dr Tobinick’s question about how he was feeling right after the injection, Tim replied,

[The pain] feels kind of pulsating right now … down my leg.  It’s not a constant pain like it was.’

Dr Tobinick replied,

‘… So [the pain has] changed in character a little bit … already’

‘Correct,’ Tim replied.  ‘I feel it in my butt still but not down the leg.’

Dr Tobinick confirmed, ‘But you feel it in your lower back and in your butt?’ 

‘Correct.’

Dr Tobinick continued, ‘But you’re starting to feel a little bit more comfortable … in general?’

‘Yeah…yes!’

 ‘… And your leg?’

‘It’s a miracle.  It’s amazing.’

‘You’re walking a lot faster … Wow!’

Tim replied, ‘Yeah I’m loving this stuff.  Once again, it worked!’

Dr Tobinick phoned Tim 3 months later on 3 July 2007 to follow up.

‘I’m wondering now how you’re feeling?’

Tim replied, ‘I am feeling like a million bucks, doctor!’

Pleased for his patient, Dr Tobinick said, ‘I love it!’

Tim continued,

‘… By the time I got back to UCLA that day [of the perispinal Etanercept injection], I was better … You would have never known I had a back problem! …’

Dr Tobinick said, ‘That’s fantastic! … You know, you had some very interesting findings. That finding of moving your right leg, making your left leg hurt, that’s a very specific finding that indicates inflammation of the nerve root.  And so, it was clear what we were treating.  And that, of course, got better, very quickly … So, it’s very interesting, scientifically … You’re better, and you didn’t have to have surgery!’

Tim replied, ‘Yes, I am too. That’s wonderful stuff you got there.’

For more details, please view Improvement within minutes in sciatica (an 8-min YouTube dated 12 Nov 2009 by the Institute of Neurological Recovery, Florida).

https://www.youtube.com/watch?v=xyfSgMoNsKY#action=share

https://www.nrimed.com/videos-by-category/back-neck-pain/

 

(5) Gerry’s Single Perispinal Etanercept Injection Offers Pain Relief in Minutes after 5 Years of Sciatica

‘Gerry’ (not his real name) suffered from sciatic pain for 5 years nonstop.  In his words, he had pain ‘every day, all day’.  Gerry tried different treatments including chiropractic and decompression treatments.

Dr Tobinick treated Gerry for sciatica via a single dose of perispinal Etanercept.  It took ‘just a few minutes’ for the Etanercept to offer lasting pain relief (as confirmed at the follow-up 2 weeks later on 9 July 2009).

For more details, please view Relief in minutes after 5 years of constant pain (a 1-min YouTube dated 6 January 2016 by the Institute of Neurological Recovery, Florida).

https://youtu.be/d0WRKmrE9Bw

https://www.nrimed.com/videos-by-category/back-neck-pain/

 

(6) Mirabelle has Improved Hand Strength After A Single Dose of Perispinal Etanercept

‘Mirabelle’ (not her real name) suffered ongoing and never-ending severe pain for 15 years.  Walking and standing up caused pain in her hips and low back.  Mirabelle had pain in both hands.  Her left hand was weaker and more painful than her right hand ever since her ski accident in 1986 or 1988.

Mirabelle was seen by nearly 30 different doctors including 10 or 11 pain specialists.

During her appointment with Dr Tobinick, Mirabelle received asingle dose of perispinal Etanercept.

When followed up 2 weeks later on 24 October 2007, Mirabelle had significantly more strength in both hands, compared to before Etanercept injection.  Her hands no longer had ‘that arthritic feeling’ (that she felt for weeks).

While there was some residual muscular pain, Mirabelle no longer had neck pain, post-Etanercept.

For more details, please view Hand improvement after treatment at the INR in 2007 (a 6-min YouTube dated 6 January 2016 by the Institute of Neurological Recovery, Florida).

https://youtu.be/6-rXP4ZEDXk

https://www.nrimed.com/videos-by-category/back-neck-pain/

 

(7) Caroline’s Sole Perispinal Etanercept Injection Relieves 25-Year Pain in 10 Minutes

At follow-up on 15 July 2009, 2 weeks after ‘Caroline’s’ (not her real name) single injection of perispinal Etanercept, Dr Tobinick asked,

‘What happened [after this injection]?’

Caroline replied, ‘… I got up … I felt … so much taller … I felt … this wonderful feeling … I stood up and it was just great … I was elated because Ihave been in pain for sooo long … [The pain was] like a knife going through you …’

Dr Tobinick continued, ‘And how long did you have the pain?’

Caroline answered, ‘Oh, I’ve had the pain … I started maybe 25 years ago …’

He asked, ‘How long?’

Caroline clarified, ‘This has been the worst, these last few years. … The last 4 years.’

Dr Tobinick asked, ‘Have you had it every day?’

She replied, ‘Just about!’

He continued, ‘Just about every day? And how many hours a day were you having the pain before you came in?’

Caroline answered, ‘Oh gosh, very, very often.’

He clarified, ‘So most of the day? …’

Caroline stated, ‘And this time when I had that injection, it’s unbelievable.’

‘How long did it take to work?’ he asked.

‘10 minutes!’

‘10 minutes,’ he confirmed.

She said, ‘Unbelievable.  It is.  It really is!

Dr Tobinick asked, ‘Has anything like this happened at all in the last few years?’   

‘No.  [Not] at all,’ she replied.  ‘It’s incredible.  I really did not believe this could happen …’

Dr Tobinick asked, ‘Have you had to take any pain medicine in the last 2 weeks?’

‘No,’ she answered.

‘Not a single … no pills?  Nothing?’ he confirmed.

‘Nothing!

‘Ok,’ he said.

‘It’s really great! …’, she said.  ‘…I’ve had … surgery … I got worse.’

Dr Tobinick asked, ‘You had surgery for your back?’

‘Yes!’

‘And you got worse?’

‘And I got worse … And yet I come to this, and it’s great! … It’s the greatest thing that’s come along. …’

‘… Alright, thank you very much,’ Dr Tobinick said.

For more details, please view the 4-minute video called Rapid pain relief after 25 years of pain July 15, 2009 (a 4-min YouTube dated 6 January 2016 by the Institute of Neurological Recovery, Florida).

https://www.youtube.com/watch?v=3ClVijm0MAA&feature=youtu.be&app=desktop

 

(8) Lola and Her Single Perispinal Etanercept Injection for Post-Stroke Pain

‘Lola’ (not her real name) suffered ongoing severe pain for almost 2 years after a stroke on 27 November 2016.  Her excruciating pain (10/10) affected the entire left side of her body including arm, breast, ribs, hip and leg.  She rarely moved her left arm nor left foot due to extreme pain.  Walking was next to impossible as her pain would only intensify with activity.

Lola tried Baclofen and Gabapentin for pain without success.

Lola booked an appointment with Dr Edward Tobinick on 20 November 2018, almost 2 years after her stroke.  After an assessment, Lola received a single perispinal Etanercept injection.

Lola enjoyed immediate pain reliefand improved left arm mobility within 10 minutes after her injection.  Her pain levels in her chest dropped to 6/10.  Lola was finally able to move her left arm without pain.  The spasticity in her left arm was also reduced.

Lola no longer had hip pain (that was 10/10 prior to injection).  The pain in her left leg and foot was gone, she was able to move her left foot for first time in 2 years and her balance was significantly improved.  Lola finally took her first steps without pain.

Overall, Lola enjoyed significantly less pain and enhanced mobility thanks to her single Etanercept injection.

According to her daughter, there was a new look in Lola’s eyes.

When Dr Tobinick asked, ‘Are you happy you’ve come?’,

Lola replied, ‘I’m very happy … And I hope I give hope to other patients too!’

For further details, please view Immediate improvement in chronic post-stroke pain nearly 2 years after stroke (a 3-minute YouTube dated 28/11/2018 by the Institute of Neurological Recovery, Florida).

https://www.youtube.com/watch?v=FLZhVil56qM

 

(9) Debbie and Her Single Perispinal Etanercept Injection for Post-Stroke Pain

‘Debbie’ (not her real name) had a massive stroke that led to mobility issues and severe, unrelenting pain in her neck, both shoulders and upper left arm.  While strong pain medication reduced some of her pain, it did not eliminate it.

Debbie was unable to get out of a chair without assistance and she required a wheelchair during shopping.  She had significant loss of function in her left hand and arm as well as loss of sensation in the left side of her body including face, hand and leg.

Debbie had her first appointment with Dr Tobinick 3 years after her stroke on 29 February 2012.

Dr Tobinick asked, ‘Do you have pain every day?’

‘Yes, every minute of every day, I’ve got pain.’

Dr Tobinick confirmed,

‘Every minute of every day?  You have constant pain?’

‘Yes’, she replied.

‘Even now, you’re in pain?’, he asked.

‘Yes, I am…’

Within only minutes after a single perispinal Etanercept injection, Debbie had significantly less pain and restored sensation to the left side of her body including face, hand and leg. The motor skills in her left hand were dramatically enhanced and she was finally able to get out of a chair without assistance.

‘How different is that from before?’

‘I can’t believe it.  It’s a miracle!’, she said with a big smile.  It’ll change my life totally!’

For further details, please view Rapid improvement in chronic post-stroke pain 3 years after stroke (a 4-minute YouTube by the Institute of Neurological Recovery, Florida).

https://www.youtube.com/watch?v=ic-6tk7MF5Y

 

Perispinal Etanercept Injections for Pain due to Bone Metastasis – Case Study (N=2)

Two patients received perispinal Etanercept injections near the site of bone metastases for pain.  This treatment led to (quoting) rapid, substantial, and sustained relief of chronic refractory pain at the treatment site’ in both patients (Tobinick, 2003).

 

Perispinal Etanercept Injections for Chronic Back and/or Neck Disc-Related Pain – A Study (N=143)

A study was done involving perispinal Etanercept injections into the spine of 143 patients with chronic back and/or neck disc-related pain.  This treatment led to significant reductions in pain, sensory dysfunction and weakness (Tobinick and Davoodifar, 2004).

 

An Australian Trial involving Perispinal Etanercept Injections for Stroke

Inspired by the outstanding results achieved after a single perispinal Etanercept injection by Dr Tobinick at the Institute of Neurological Recovery (INR), Florida, a clinical trial is now underway for stroke patients in Australia.

Quoting,

‘The project will enable more Australians of working age who have had a stroke to access new … treatment options to aid their recovery.’

 

While results are not yet finalised, further details are here:

 

  • $1 million to support the rehabilitation of stroke survivors (6 October 2018)

https://www.health.gov.au/ministers/the-hon-greg-hunt-mp/media/1-million-to-support-the-rehabilitation-of-stroke-survivors            

http://www.nrimed.com/wp-content/uploads/GH134.pdf

 

  • Australian Government designates funds to advance Perispinal Etanercept stroke research in Australia (8 October 2018)

http://www.strokebreakthrough.com/blog-posts/uncategorized/australian-government-designates-funds-to-advance-perispinal-etanercept-stroke-research-in-australia/

Summary

More research into anti-TNF drug treatment for CRPS, sciatica, post-stroke pain and other nerve pain conditions is encouraged.  Such studies should confirm whether localised TNF levels are elevated in CRPS-affected limbs and other pain-affected areas in the first place.  If yes, analysis is necessary whether any anti-TNF drug treatment leads to a significant reduction in these elevated localised TNF levels, and if yes, whether this is also accompanied by reduced pain (etc).  Induced skin blisters or skin biopsies may be necessary to confirm localised TNF levels in CRPS-affected limbs and other pain-affected regions, both ‘before’ and ‘after’ anti-TNF drug treatment.

NOTE:  If localised TNF levels are already low to begin with (prior to anti-TNF drug treatment), anti-TNF drug treatment is (likely) not indicated.

Possible adverse effects also need to be considered prior to anti-TNF drug treatment.  Medical supervision is always advised.

 

Wishing all pain patients less pain,

Sabina Walker

Masters Appl. Science (Neuroscience)

Blogger, Pain Matters (in WordPress)

painmatters.wordpress.com

and

Author of soon-to-be published book called Pain Matters 

Twitter

@SabinaWalker18

 

For more information about Dr Tobinick’s treatment involving perispinal Etanercept for nerve pain, please see:

https://www.nrimed.com

Patient videos (N=307) by the Institute of Neurological Recovery, Florida:

https://www.nrimed.com/videos-by-category/

https://www.nrimed.com/videos-by-category/back-neck-pain/

https://www.nrimed.com/videos-by-category/stroke-pain-videos/

Scientific publications by Dr Tobinick and his peers:

https://www.nrimed.com/inr-scientific-publications/

Media stories:

http://www.nrimed.com/about/media-stories/

Blog by the Institute of Neurological Recovery, Florida:

https://www.nrimed.com/blog/

Please note that treatment involving perispinal Etanercept injection is protected by multiple patents owned by Edward Tobinick MD including U.S. patents 6 015 557; 6 177 077; 6 419 944; 6 537 549 and Australian patent 758 523 (Tobinick and Davoodifar, 2004).

 

PS YOU DON’T HAVE TO READ THE FOLLOWING UNLESS YOU ARE INTERESTED IN THE UNDERLYING SCIENCE 

POSSIBLE MECHANISMS OF ANTI-TNF DRUG THERAPY IN CRPS NERVE PAIN

Anti-TNF drugs (e.g. InfliximabEtanercept) are TNF monoclonal antibodies that selectively block TNF, hence limiting the pro-inflammatory process.

The reduction of TNF and other pro-inflammatory mediators (via anti-TNF drug therapy or otherwise) may alleviate certain painful symptoms in CRPS, sciatica, post-stroke pain and other severe nerve pain conditions.

Ongoing trials are warranted including analysis of side effects.

For further details, please refer to all papers by Edward Tobinick MD and his peers.

Other papers are also available in the References including 24-page Review Paper by Sabina Walker and Prof. Peter Drummond. In particular, please see pages 1790 – 1791, plus related references on page 1804 (included below).

 

REFERENCES

Selected Scientific Publications by Dr Tobinick and His Peers

https://www.nrimed.com/inr-scientific-publications/

(1A) Ignatowski TA et al. Perispinal Etanercept for Post-Stroke Neurological and Cognitive Dysfunction: Scientific Rationale and Current Evidence.CNS Drugs(August 2014); 28(8): 679-697.

https://www.strokebreakthrough.com/wp-content/uploads/PSE.post-stroke.Scientific-Rationale.August2014.pdf

(1B) Tobinick E and Davoodifar S.Efficacy of etanercept delivered by perispinal administration for chronic back and/or neck disc-related pain: a study of clinical observations in 143 patients. Davoodifar S. Curr Med Res Opin(July 2004); 20(7): 1075-85.

https://www.ncbi.nlm.nih.gov/pubmed/15265252

(1C) Tobinick, Edward et al. Immediate Neurological Recovery Following Perispinal Etanercept Years After Brain InjuryClin Drug Investig(May 2014); 34(5): 361-6.

https://www.ncbi.nlm.nih.gov/pubmed/24647830

(1D) Tobinick, Edward et al.On Overcoming Barriers to Application of Neuroinflammation Research. In: Abreu GEA, ed. Mechanisms of Neuroinflammation: InTechOpen; 2017.

https://www.nrimed.com/wp-content/uploads/Chapter7.overcoming.barriers.pdf

(1E) Tobinick, Edward. Perispinal Delivery of CNS Drugs. CNS Drugs (2016); 30(6): 469-80.

https://www.ncbi.nlm.nih.gov/pubmed/27120182

(1F) Tobinick, Edward. Perispinal etanercept advances as a neurotherapeutic.Expert Review of Neurotherapeutics (2018); 1-3.

https://www.nrimed.com/wp-content/uploads/Perispinal-etanercept-advances-as-a-neurotherapeutic-1.pdf

(1G) Tobinick, Edward. Perispinal etanercept: a new therapeutic paradigm in neurology.

Expert Review of Neurotherapeutics (June 2010); 10(6): 985-1002.

https://www.strokebreakthrough.com/wp-content/uploads/PSE.ERN2_2.pdf

(1H) Tobinick, Edward. Perispinal etanercept for neuroinflammatory disorders.Drug Discovery Today(Feb 2009); 14(3-4): 168-77.

https://www.ncbi.nlm.nih.gov/pubmed/19027875

(1I) Tobinick, Edward et al.Perispinal Etanercept for Traumatic Brain Injury.Chapter 7, pp. 109-29, in New Therapeutics for Traumatic Brain Injury, Cambridge, Mass.: Academic Press. 2017.

https://www.sciencedirect.com/science/article/pii/B9780128026861000079

(1J) Tobinick, Edward et al.Rapid intracerebroventricular delivery of Cu-DOTA-etanercept after peripheral administration demonstrated by PET imagingBMC Res Notes(27 Feb 2009); 2: 28.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651903/pdf/1756-0500-2-28.pdf

(1K) Tobinick, Edward L. Targeted etanercept for treatment-refractory pain due to bone metastasis: two case reports. Clinical Therapeutics. (Aug 2003); 25(8): 2279-88.

https://www.ncbi.nlm.nih.gov/pubmed/14512134

(1L) Tuttolomondo et al.Studies of Selective TNF Inhibitors in the Treatment of Brain Injury from Stroke and Trauma: A Review of Evidence to Date. Drug Design, Development and Therapy(Nov 2014); 8: 2221-2239.

https://www.ncbi.nlm.nih.gov/pubmed/25422582

Other Scientific Publications 

(2) Karppinen et al; Tumor necrosis factor-alpha monoclonal antibody, infliximab, used to manage severe sciatica. Spine 2003;28:750–4.

(3) Manning; New and emerging pharmacological targets for neuropathic pain. Curr Pain Headache Rep 2004;8:192–8.

(4) Korhonen et al; The treatment of disc-herniation-induced sciatica with infliximab: One-year follow-up results of FIRST II, a randomized controlled trial. Spine 2006;31:2759–66.

(5) Burnett, Day; Recent advancements in the treatment of lumbar radicular pain. Curr Opin Anaesthesiol 2008;21:452–6.

(6) Cohen et al; Randomized, double-blind, placebo-controlled, dose-response, and preclinical safety study of transforaminal epidural etanercept for the treatment of sciatica. Anesthesiology 2009;110:1116–26.

(7) Lipsky et al; Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study group. N Engl J Med 2000;343:1594–602.

(8) Emery, Buch; Treating rheumatoid arthritis with tumor necrosis factor alpha blockade. BMJ 2002; 234:212–213.

(9) Blam et al; Integrating anti-tumor necrosis factor in inflammatory bowel disease: current and future perspectives. Am J Gastroenterol 2001;96:1977–1997.

Scientific Publication by Sabina Walker (Blogger of Pain Matters) and Professor Peter Drummond

(10) Sabina Walker, Peter D. Drummond; Implications of a Local Overproduction of Tumor Necrosis Factor-α in Complex Regional Pain Syndrome [Review Paper, 24 pages]; Pain Medicine (Dec 2011), 12 (12), 1784–1807.

In particular, please refer to pages 1790 – 1791, plus related references on page 1804 (also listed above).

http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4637.2011.01273.x/abstract

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Ziconotide (Prialt) for Nerve Pain Including CRPS?

Dear Pain Matters blog readers,

For some pain sufferers, pain relief may be offered (in part or in full) by a component of the venom of an ocean-dwelling cone snail called Conus magus.

Before continuing, I would like to take a moment to celebrate the beauty, power, and energy (while also respecting the dangers) of our oceans with all its amazing creatures (including, of course, deadly cone snails).  I took this photo from BELOW the ocean waves (while snorkelling yesterday).

ZICONOTIDE (PRIALT) AND SEVERE PAIN

Today’s blog post is on Ziconotide (Prialt).  Ziconotide is the synthetic equivalent of a naturally-occurring conopeptide called SNX-111 (or omega-conotoxin MVIIA), a component of the venom of the marine cone snail, Conus magus.

Ziconotide, a novel non-opioid drug, can be used to treat patients with severe chronic pain.  It works by selectively and potently blocking the neuronal N-type calcium channel.

Some patients with severe chronic pain may receive significant pain relief from Ziconotide, either as sole treatment (monotherapy) or with other treatments.  Ziconotide is able to maintain its analgesic effects for month(s), even after a single infusion treatment.

Ziconotide treatment does not result in tolerance, dependence, nor respiratory depression (unlike opioids).  However, there can be adverse effects, especially if dosages are too high, or titrated too quickly (see below).

SUCCESSFUL CASE STUDIES INVOLVING ZICONOTIDE (PRIALT) AND SEVERE PAIN 

(1) Severe Intractable Deafferentation Pain Plus Phantom Limb Pain –

A 43-year old male patient suffered (quoting) ‘refractory, severe deafferentation pain’ and phantom limb pain for 23 years, following brachial plexus avulsion and consequent amputation.

Following  administration of SNX-111 (Ziconotide) via continuous intrathecal infusion via a cervical catheter, this patient had complete pain relief as well as (quoting) ‘elimination of hyperesthesia and allodynia‘.

Complete pain relief was still provided to this patient even after dosages were reduced to eliminate side effects.  Thus, SNX-111 (Ziconotide) may offer potent pain relief for both malignant and nonmalignant pain conditions (Brose et al, 1997).

(2) Three (3) Nerve Pain Patients and Ziconotide Infusion –

The 1st patient, with chronic complex regional pain syndrome (CRPS) in the leg, received a single Ziconotide infusion treatment.  This resulted in temporary and complete pain relief.  (There were adverse effects, however.)

The 2nd patient (with painful lumbar radiculitis) received complete (albeit temporary) pain relief following a test dose of Ziconotide infusion.  (There were also side effects.)

The 3rd patient, with persistent bilateral leg and foot nerve pain due to AIDS and related drug therapy, obtained significant pain relief following long-term continuous intrathecal infusion (Wermeling et al, 2006).

(3) Ziconotide in a 16-year-old Male With CRPS in Both Legs –

A 16-year-old boy with CRPS in both legs was given Ziconotide for 3 years.  Pain was reduced at 6 weeks, and a normal gait was achieved at 7 months.  The patient reported NIL pain after 3 years of Ziconotide therapy.  Side effects included urinary retention and depression (Webster, 2005).

(4) Ziconotide in a 17-year-old Female With Chronic CRPS in Right Lower Leg (Initiated by an Ankle Sprain at 13) –

A 17-year-old girl, who was wheelchair-bound due to chronic CRPS in her right lower leg, was given Ziconotide (and other medications) via intrathecal catheter.  As dosages were increased, the swelling in her leg and foot decreased.  At greater dosages, pain levels further decreased and the ‘desquamating skin’ receded toward her right foot.  At times, the edema disappeared completely.

As dosages were further increased, most of her skin scales had disappeared and her foot appeared pink.  Foot movement was regained, as was her quality of sleep that now included a bed cover.  By now, she had also progressed from a wheelchair to crutches.

Further months of Ziconotide therapy brought her VAS Pain Score down to 4 (from 8, pre-Ziconotide).  By now, ambulation and function was greatly improved, with little or no allodynia nor hyperalgesia.

Significant side effects were not observed, and this was attributed to a slow titration of Ziconotide (Stanton-Hicks et al; 2006). 

(5) Ziconotide for 7 CRPS Patients –

Five (5) of 7 CRPS patients had (quoting) ‘substantial improvement in pain, edema, skin abnormalities, and/or mobility with ziconotide therapy’.

In fact, 2 patients had complete pain relief and as such, discontinued Ziconotide treatment altogether.  

A 3rd patient had significantly reduced edema as well as decreased skin trophic changes, following Ziconotide infusion.

Adverse events (including depression, anxiety, hallucinations, and urinary retention) were managed via dose reductions/discontinuation, or otherwise (Kapural et al, 2009).

DRAWBACKS/ADVERSE EFFECTS OF ZICONOTIDE (PRIALT) 

Several drawbacks and possible adverse effects must be noted including:

Ziconotide requires intrathecal administration.

NB  A properly performed trial of ziconotide infusion should always be done first before consideration is made whether to surgically implant an intrathecal device on a permanent basis, or not.  This trial phase is absolutely necessary to ascertain whether a patient will obtain pain relief from ziconotide in the first place (Knight et al, 2007);

and

– There is a risk of one or more adverse effects including dizziness, nausea, ataxia, abnormal gait, headache, abnormal sensations, nystagmus (involuntary eye movement), and/or confusion.

To minimise adverse effects while also maximising pain relief, initial dosages should be low, titrated slowly, and gradually increased as necessary.  It may a month (or more) to achieve a fine balance between minimal adverse effects and maximal pain relief (Webster, 2005).

Wishing all pain patients hope, inspiration, and less pain.

Sabina Walker

REFERENCES

SUCCESSFUL CASE STUDIES INVOLVING ZICONOTIDE (PRIALT) AND SEVERE PAIN

(1) Brose et al; Use of intrathecal SNX-111, a novel, N-type, voltage-sensitive, calcium channel blocker, in the management of intractable brachial plexus avulsion pain; Clin J Pain (Sep 1997);13(3):256-9.

http://www.ncbi.nlm.nih.gov/pubmed/9303259

(2) Wermeling et alZiconotide Infusion for Severe Chronic Pain: Case Series of Patients With Neuropathic Pain; Pharmacotherapy (Mar 2006); 26(3):395-402.

http://www.ncbi.nlm.nih.gov/pubmed/16503720

(3) Webster; Ziconotide in Complex Regional Pain Syndrome (2005)

http://www.rsds.org/Research_Articles/Ziconotide.htm

(4) Stanton-Hicks et al;  An Effective Treatment of Severe Complex Regional Pain Syndrome Type 1 in a Child Using High Doses of Intrathecal ZiconotideJ Pain Symp Man (Dec 2006); 32(6):509-11.

doi:10.1016/j.jpainsymman.2006.08.002

http://www.rsds.org/pdfsall/J_Pain_Symp_Man_2006_32_6_pg509.pdf

(5) Kapural et al; Intrathecal ziconotide for complex regional pain syndrome: seven case reports; Pain Pract (Jul-Aug 2009); 9(4):296-303.

doi: 10.1111/j.1533-2500.2009.00289.x.

http://www.ncbi.nlm.nih.gov/pubmed/19500276

(6) Smith, Deer; Safety and efficacy of intrathecal ziconotide in the management of severe chronic pain; Therapeutics and Clinical Risk Management (Jun 2009); 5(3):521–534.

http://www.ncbi.nlm.nih.gov/pubmed/19707262

(7) Caraway et al; Intrathecal Therapy Trials with Ziconotide – A Trialing Protocol Before Initiation of Long-Term Ziconotide Intrathecal Therapy is Presented.

http://www.practicalpainmanagement.com/treatments/interventional/pumps/intrathecal-therapy-trials-ziconotide

MORE ON ZICONOTIDE (PRIALT)

(8) Knight et al; Implantable Intrathecal Pumps for Chronic Pain: Highlights and Updates; Croat Med J (Feb 2007); 48(1):22-34.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2080496/

(9) Miljanich; Ziconotide: Neuronal calcium channel blocker for treating severe chronic pain. Curr Med Chem (2004); 11:3029–3040.

doi: 10.2174/0929867043363884.

http://www.ncbi.nlm.nih.gov/pubmed/15578997

(10) Bowersox, Luther; Pharmacotherapeutic potential of omega-conotoxin MVIIA (SNX-111), an N-type neuronal calcium channel blocker found in the venom of Conus magus. Toxicon (Nov 1998); 36(11), 1651–1658.

(11) Rauck et al; Intrathecal Ziconotide for Neuropathic Pain: A Review; Pain Practice (2009); 9:327–337.

doi:10.1111/j.1533-2500.2009.00303.x

http://onlinelibrary.wiley.com/doi/10.1111/j.1533-2500.2009.00303.x/abstract

CONOTOXINS IN GENERAL  

(12) Holmes, David; Conotoxins: how a deadly snail could help ease pain; The Lancet Neurology (Sept 2014); 13(9):867-868.

doi:10.1016/S1474-4422(14)70183-8

http://download.thelancet.com/pdfs/journals/laneur/PIIS1474442214701838.pdf?id=gaa2FpnFy-oV877zjnrMu

(13) Blog post by another blogger, ‘Baldscientist’

Magnificent Conotoxins – Expanded (27 July 2014)

http://baldscientist.wordpress.com/2014/07/27/magnificent-conotoxins-expanded/

The blog post by ‘Baldscientist’ includes these References: 

(13A) Brady, Baell, Norton; Strategies for the development of conotoxins as new therapeutic leads; Mar Drugs (Jul 2013); 11(7): 2293–2313.

doi: 10.3390/md11072293

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736424/

(13B) Essack, Bajic, Archer; Conotoxins that confer therapeutic possibilities. Mar Drugs (2012); 10(6):1244-65.

doi:10.3390/md10061244

http://www.mdpi.com/1660-3397/10/6/1244/htm

Anti-TNF Drugs for CRPS and Other Chronic Pain Conditions (1/2)

Dear Pain Matters blog readers,

Introduction

Infliximab, Etanercept and other selective anti-TNF drugs are sometimes used to treat:

  • Complex regional pain syndrome (CRPS);
  • Lumbar radicular pain;
  • Sciatica;
  • Post-stroke pain;
  • Rheumatoid arthritis;
  • Crohn’s disease; and
  • Other painful conditions.

This blog post will explore anti-TNF drugs for CRPS.

A second blog post will explore a single perispinal Etanercept injection for some patients with sciatica, post-stoke pain and other painful conditions.

A SINGLE Perispinal Etanercept Injection Offers Relief from Severe Chronic Pain including Sciatica and Post-Stroke Pain (2/2)

Complex Regional Pain Syndrome (CRPS) and Anti-TNF Drug Trial

Several European studies showed promising results following anti-TNF drug (Infliximab) trials in CRPS patients.

(1) Infliximab Treatment for 2 CRPS Patients 

In the 1st Infliximab paper, pain decreased in 2 CRPS patients.

  • 1st Patient (Female, 50):  Chronic CRPS, Duration ~ 5 years
  • 2nd Patient (Female, 55): Acute CRPS, Duration ~ 2 months, caused by left arm Colles’ fracture

Blister fluid from the CRPS limbs of both patients showed significant reductions in localised tumor necrosis factor-alpha (TNF) and IL-6 following Infliximab treatment.

More importantly (from the patients’ perspective), there was:

  • Reduced pain;
  • Decreased vascular disturbances;
  • Less swelling/edema;
  • Enhanced motor function; and
  • Improved symptoms (Huygen et al, 2004).

(2) Infliximab Treatment for 1 CRPS Patient –

In the 2nd Infliximab paper, pain decreased in 1 patient with acute CRPS.  Specifically, a female patient (62) with acute CRPS for 3 months, caused by left hand Colles’ fracture, showed near-complete remission following Infliximab treatment for 8 weeks (Bernateck et al, 2007).

(3) Infliximab Trial for CRPS (7 Cases, Plus Placebo Group) –

Six (6) CRPS patients were treated with Infliximab, while another 7 CRPS patients were given placebo.  There was greater reduction in TNF levels in the Infliximab-treated patients (compared to placebo).  However, for various reasons, this study was discontinued (Dirckx et al, 2013; Nederlands Trial Register 449 ISRCTN 75765780).

Summary

More research into anti-TNF drug treatment for CRPS is warranted.  Such studies should confirm whether localised TNF levels are elevated in CRPS-affected limbs in the first place.  If yes, analysis is necessary whether any anti-TNF drug treatment leads to a significant reduction in these elevated localised TNF levels, and if yes, whether this is also accompanied by reduced pain (etc).  Induced skin blisters or skin biopsies may be necessary to confirm localised TNF levels in CRPS-affected limbs, both ‘before’ and ‘after’ anti-TNF drug treatment.

NOTE:  If localised TNF levels are already low to begin with (prior to anti-TNF drug treatment), anti-TNF drug treatment is (likely) not justified.

Possible adverse effects also need to be considered prior to anti-TNF drug treatment.

 

Wishing all pain patients less pain,

Sabina Walker

PS YOU DON’T HAVE TO READ THE FOLLOWING UNLESS YOU ARE VERY INTERESTED IN SCIENCE –

POSSIBLE MECHANISMS OF ANTI-TNF DRUG THERAPY IN CRPS NERVE PAIN

Anti-TNF drugs (e.g. InfliximabEtanercept) are TNF monoclonal antibodies that selectively block TNF, hence limiting the pro-inflammatory process.

The reduction of TNF and other pro-inflammatory mediators (via anti-TNF drug therapy, or otherwise) may alleviate certain painful symptoms in CRPS , sciatica and other nerve pain conditions.

Ongoing trials are warranted including analysis of side effects.

For further details, please refer to 24-page Review Paper by Sabina Walker and Prof. Peter Drummond. In particular, please see pages 1790 – 1791, plus related references on page 1804 (listed below).

REFERENCES:

Anti-TNF Drug Therapy For Lumbar Radicular Pain Including Severe Sciatica, Rheumatoid Arthritis, and Crohn’s disease

(1) Karppinen et al; Tumor necrosis factor-alpha monoclonal antibody, infliximab, used to manage severe sciatica. Spine 2003;28:750–4.

(2) Manning; New and emerging pharmacological targets for neuropathic pain. Curr Pain Headache Rep 2004;8:192–8.

(3) Korhonen et al; The treatment of disc-herniation-induced sciatica with infliximab: One-year follow-up results of FIRST II, a randomized controlled trial. Spine 2006;31:2759–66.

(4) Burnett, Day; Recent advancements in the treatment of lumbar radicular pain. Curr Opin Anaesthesiol 2008;21:452–6.

(5) Cohen et al; Randomized, double-blind, placebo-controlled, dose-response, and preclinical safety study of transforaminal epidural etanercept for the treatment of sciatica. Anesthesiology 2009;110:1116–26.

(6) Lipsky et al; Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study group. N Engl J Med 2000;343:1594–602.

(7) Emery, Buch; Treating rheumatoid arthritis with tumor necrosis factor alpha blockade. BMJ 2002; 234:212–213.

(8) Blam et al; Integrating anti-tumor necrosis factor in inflammatory bowel disease: current and future perspectives. Am J Gastroenterol 2001;96:1977–1997.

Anti-TNF Drug Therapy For Complex Regional Pain Syndrome (CRPS)

(9) Huygen et al. Successful treatment of CRPS 1 with anti-TNF. J Pain Symptom Manage 2004;27:101–3.

http://www.ncbi.nlm.nih.gov/pubmed/15157033

(10) Bernateck et al. Successful intravenous regional block with low-dose tumor necrosis factor-a antibody infliximab for treatment of complex regional pain syndrome 1. Anesth Analg 2007;105:1148–51.

http://www.rsds.org/pdfsall/Bernateck_Rolke.pdf

(11A) Dirckx, Groeneweg, Wesseldijk, Stronks, Huygen; Report of a Preliminary Discontinued Double-Blind, Randomized, Placebo-Controlled Trial of the Anti-TNF-α Chimeric Monoclonal Antibody Infliximab in Complex Regional Pain Syndrome; Pain Practice (Nov 2013); 13(8):633–640.

DOI: 10.1111/papr.12078

http://onlinelibrary.wiley.com/doi/10.1111/papr.12078/abstract

(11B) Nederlands Trial Register 449 ISRCTN 75765780

http://www.controlled-trials.com/ISRCTN75765780/crps

(12) Sabina Walker, Peter D. Drummond; Implications of a Local Overproduction of Tumor Necrosis Factor-α in Complex Regional Pain Syndrome [Review Paper, 24 pages]; Pain Medicine (Dec 2011), 12 (12), 1784–1807.

In particular, please refer to pages 1790 – 1791, plus related references on page 1804 (also listed above).

http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4637.2011.01273.x/abstract