Good News! Chronic Migraines/Headaches Exceeding 25 Years Have Finally Ended For Eva – After Only 2 Consultations with a ‘Gonstead’ Chiropractor!

Dear Pain Matters blog readers,

Two days ago, my American friend and I went to a cafe where we were served by a nice woman named Eva.

Our conversation with Eva started because I was admiring her 21 earrings, 10 in one ear and 11 in the other ear!  As we discussed her 21 beautiful earrings, the topic of ‘earrings and X-Rays’ (somehow) came up.

Eva told us that she used to endure frequent, painful, and disabling migraines/headaches (that lasted many days at a time) for more than 25 years (until August 2013).  Eva does not know how these painful migraines/headaches started, although she does remember that they first started when she was only 15 or 16 years old.

Eva literally tried everything (without success) in her bid to get rid of her painful and disabling migraines/headaches including:

– Prescription drugs (costing more than $1,000 per year);

– CT scans;

– MRI scans;

– Stress clinics;

– Homeopathy;

– Acupuncture (that did help with nausea and vomiting due to her migraines, but that did not reduce migraine pain); and

– Psychologist (for stress caused by painful migraines/headaches).

Sadly, nothing helped with the painful and disabling migraines/headaches for more than 25 years.

Six (6) years ago, she gave birth to a beautiful and healthy baby girl.  However, even as she lovingly nurtured and fed her baby girl, her painful migraines/headaches persisted.

Eva’s chronic and painful migraines/headaches robbed her of 25 years of her life including her youth, health, sleep, career, and social life, including 5 years’ quality time with her daughter (now 6).

Eva spent up to 5 consecutive days and nights in a dark and quiet bedroom, lying very still (but unable to sleep due to migraines), right next to ‘her vomit bowl’ – that was often used for vomiting.  As a result, she missed many days at work, and her social life was severely affected.  She added that often, she recorded 23 to 25 days of debilitating migraines per month, following the birth of her daughter.

‘What kind of life is this?’, she asked.  Finally, on a Thursday in August 2013, Eva couldn’t take it anymore.  She decided that she had to try something new and different for her painful migraines/headaches (for her and her family’s sake).

As she walked past the local Chiropractor/Exercise Physiologist’s practice (near her home in the eastern suburbs of Sydney, Australia), she stopped and walked in for the very 1st time (after having passed by here many times before).  She asked the staff whether she needed a Referral to see the Chiropractor/Exercise Physiologist (also a Gonstead Chiropractor), and the staff replied ‘no’.  Eva added that she desperately and urgently needed help for her migraines/headaches, as she couldn’t take her migraines anymore.  Fortunately for her, the Gonstead Chiropractor was available to see her that very same day.  She was requested to bring in copies of all her imaging reports.

Here is the best part of Eva’s 25-year long, painful and unpleasant journey with migraines/headaches:  It finally ended that same week in August 2013!!  After only 2 consultations with this Gonstead Chiropractor (and a 3rd Follow-Up Visit, 2 days later), Eva’s painful migraines/headaches disappeared FOR THE VERY FIRST TIME, AFTER MORE THAN 25 YEARS OF PAIN AND SUFFERING!  Imagine that!

At Eva’s 1st Consultation in August 2013, her Gonstead Chiropractor took a detailed clinical history including a review of her imaging reports.  As part of his thorough physical examination, he also used a Nervoscope instrument.

Quoting from the Gonstead Chiropractic Society Australia website:

“The Nervoscope detects uneven distributions of heat along the spine which can be indicative of inflammation and nerve pressure. This instrument is guided down the length of your back and feels like two fingers gliding down each side of your spine.”

https://www.gonstead.com.au/what-gonstead

Thereafter, her Gonstead Chiropractor gently treated her neck region with his hands (consistent with the ‘Gonstead System of Chiropractic’ approach).  Eva added that her Gonstead Chiropractor never exerted any strong force nor any painful manipulation during his treatment.

Even after Eva’s 1st (45-minute) consultation/treatment, Eva already knew ‘something was working’.  Her dizziness was gone!  And her vision (that was affected during her severe migraine attacks) was now clear!

The Gonstead Chiropractor suggested that Eva see him again in 2 days (on Saturday).  After this 2nd treatment (15-minutes) on Saturday, Eva confirmed that ALL the nasty and unpleasant symptoms of her painful migraines/headaches had finally disappeared altogether.

With only 1 exception, Eva has not had a single migraine/headache since these 2 consultations in August 2013 with her Gonstead Chiropractor.  Eva’s migraine briefly returned while on a recent holiday in Europe (where she had slept on very large, firm European pillows).  As soon as Eva returned to Sydney, she promptly went back to her Gonstead Chiropractor for treatment.  After only 1 short session (that included very gentle treatment of her neck), she was ‘as good as new’ again.  Importantly, her migraines/headaches have not returned since, and she is now living a pain-free life, without migraines nor headaches.

Eva has routine Follow-Up Appointments with her local Gonstead Chiropractor every 6 months, ‘just to make sure everything is OK’.  So far, so good…..no further treatments are necessary…..and no more painful migraines for Eva.

It is important to note that pain mechanisms vary from one migraine sufferer to the next.  In Eva’s case, the migraines were structural/anatomical in origin, and related to her neck region (that was virtually impossible to detect without the aid of a Nervoscope).

While Eva’s solution for her 25-year painful migraines/headaches may not work for everyone, her decision to see an experienced, qualified and gentle Gonstead Chiropractor is certainly worthwhile.

Different pain treatments may work for different people with chronic pain/migraines/headaches.  It may take a while to find the correct and effective pain treatment(s).

The moral of this story is:

Never, ever give up hope!  After all, Eva never gave up, even after 25 years!

If you have chronic migraines/headaches, please try different treatments … including Eva’s approach.

Thanks to 2 treatments by her Gonstead Chiropractor, Eva was finally able to stop her 25-year long chronic migraines/headaches.

Now in her very early 40’s, Eva is finally able to enjoy her life as a mother and wife, without also enduring constant debilitating and painful migraines/headaches.

One thing is certain to Eva:  The joys of motherhood without painful migraines is a true gift that words can never fully describe.  Her migraine nightmare is finally over.

On behalf of all Pain Matters blog readers, thank you, Eva, for sharing your story about your 25-year long journey with painful migraines – that finally ended in August 2013, after 2 visits within 2 days with a Gonstead Chiropractor (Eva’s own guardian angel).

I hope you all enjoyed today’s feature story about Eva, that may offer hope and inspiration to many migraine sufferers.!

Sabina Walker (Blogger of Pain Matters;  Master Appl. Sc. (Neurosc.))

REFERENCES

(1) What is Gonstead?

Gonstead Chiropractic Society Australia

https://www.gonstead.com.au/what-gonstead

Advertisements

Stem Cells in the Olfactory Bulb for Certain Neurological Conditions Including Spinal Cord Injury

Dear Pain Matters blog readers,

It is worth adding more to Friday’s blog post dated 21 November 2014.

https://painmatters.wordpress.com/2014/11/21/stem-cell-treatment-of-spinal-cord-injury-one-case/

A QUESTION WHETHER STEM CELL TREATMENT COULD ALSO REDUCE NERVE PAIN IN SOME SPINAL CORD INJURY PATIENTS?

Many patients with spinal cord injury also suffer severe nerve pain.  Could stem cell treatment for spinal cord injury (potentially) result in:

(1) enhanced motor and sensory function; and

(2) reduced nerve pain

in some patients?

A recent Review Paper suggested that stem cells may have the following 2 beneficial effects:

(1) regenerative effects that may enhance motor and sensory functions (eg in spinal cord injury patients); and

(2) decreased pro-inflammatory response that may lead to reduced nerve pain.

It is possible that a reduced pro-inflammatory response (consequently, reduced nerve pain) may be a prerequisite before the stem cells’ regenerative effects can take place.  Thus, the mechanisms that underlie the stem cells’ beneficial effects on nerve pain may be different from those that underlie their regenerative effects (Franchi et al, 2014).

It would be useful to include spinal cord injury patients that also have spinal cord injury pain in upcoming stem cell trials.

If research can show that stem cell treatment can, at times, result in BOTH: 

(1) enhanced motor/sensory function; as well as

(2) reduced nerve pain,

this would be a immense breakthrough for medical science.

MORE ON STEM CELLS IN THE OLFACTORY BULB

Stem cells are available in different parts of your body.  Recently, it was shown that the olfactory bulb (in the upper nasal cavity, used in the sense of smell) can be a rich source of olfactory ensheathing cells and olfactory nerve fibroblasts.

Specifically, researchers reported that olfactory ensheathing cells and olfactory nerve fibroblasts were taken from the olfactory bulb, placed in a culture for 2 weeks, and subsequently transplanted into an injured spinal cord of a paralysed patient named Darek Fidyka, a 38-year old man who suffered paralysis from the chest down following a stabbing in 2010.

https://painmatters.wordpress.com/2014/11/21/stem-cell-treatment-of-spinal-cord-injury-one-case/

Given the amazing regenerative capacity of these olfactory bulb stem cells, ongoing research into the transplantation of these stem cells into injured or diseased body/brain regions is warranted.

One day, perhaps, the ‘miracle of stem cells’ may be a standard medical treatment option, and the transplantation of stem cells will be as normal as ‘planting seeds in a garden’.

WHERE TO FROM HERE?

Other questions arise.  For example, can the regenerative stem cells from the olfactory bulb also be transplanted (via autologous stem cell transplant) into different parts of the body including spinal cord and brain?

If yes, could autologous stem cell transplant (using stem cells from one’s own olfactory bulb) be used one day to treat people with:

Diabetes (Kuwabara & Asashima, 2012);

Spinal cord injury; and/or

– Other neuronal diseases including Amyotrophic Lateral Sclerosis (aka Lou Gehrig’s Disease, or Motor Neurone Disease), Parkinson’s Disease, and some Post-Stroke conditions (eg Locked-In-Syndrome)?

Research into non-embryonic sources of stem cells is warranted (Franchi et al, 2014).  Permanent damage does not occur when stem cells are removed from the olfactory bulb (that is also relatively accessible via surgery).

The possibilities of stem cell research are endless.

I hope that stem cell research offers hope and inspiration to all people suffering from pain, limited mobility, and reduced sensory function.

Sabina Walker

“Imagination is more important than knowledge. For knowledge is limited to all we now know and understand, while imagination embraces the entire world, and all there ever will be to know and understand.” 

Einstein

REFERENCES

(1) Kuwabara, Asashima (Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Japan)

Regenerative medicine using adult neural stem cells: the potential for diabetes therapy and other pharmaceutical applications; J Mol Cell Biol (2012):4(3):133-139.

doi: 10.1093/jmcb/mjs016

http://jmcb.oxfordjournals.org/content/4/3/133.full.pdf+html

(2) Olfactory Bulb Stem Cells And Lou Gehrig’s Disease
Johns Hopkins Medical Institutions
27 October, 2004

http://www.sciencedaily.com/releases/2004/10/041025121323.htm

(3) Franchi et al; Adult Stem Cell as New Advanced Therapy for Experimental Neuropathic Pain Treatment; BioMed Research International (2014); Article ID 470983, Pages 1-10 (10 pages).

doi: 10.1155/2014/470983

PMCID: PMC4147203

http://www.hindawi.com/journals/bmri/2014/470983/

MORE REFERENCES

(FOR READERS WHO WANT TO LEARN MORE ABOUT STEM CELLS IN THE OLFACTORY BULB….OTHERWISE JUST IGNORE THE FOLLOWING PAPERS)

(4) Pagano et al; Isolation and characterization of neural stem cells from the adult human olfactory bulb. Stem Cells. 2000;18(4):295-300.

http://www.ncbi.nlm.nih.gov/pubmed/10924096

(5) MacKay-Sim; Stem cells and their niche in the adult olfactory mucosa. Archives Italiennes de Biologie (2010):148:47-58.

http://www98.griffith.edu.au/dspace/bitstream/handle/10072/35444/64019_1.pdf?sequence=1&isAllowed=y

(6) Moreno-Estellés et al; Symmetric expansion of neural stem cells from the adult olfactory bulb is driven by astrocytes via WNT7A. Stem Cells (Dec 2012);30(12):2796-2809.

doi: 10.1002/stem.1243.

http://www.ncbi.nlm.nih.gov/pubmed/22987443

(7) Gritti et al; Multipotent neural stem cells reside into the rostral extension and olfactory bulb of adult rodents. J Neurosci (Jan 2002);22(2):437-445.

http://www.jneurosci.org/content/22/2/437.full.pdf

(8) Liu & Martin; Olfactory bulb core is a rich source of neural progenitor and stem cells in adult rodent and human. J Comp Neurol (May 2003);459(4):368-91.

http://www.ncbi.nlm.nih.gov/pubmed/12687705

Partial Recovery from Paralysis Following Stem Cell Treatment – A Case Study

Dear Pain Matters blog readers,

Here’s some positive news for patients with spinal cord injury!  It was recently reported that stem cell treatment in a patient with spinal cord injury resulted in partial recovery.  

While more studies are needed, a 3-minute video (see BBC News link) introduces Darek Fidyka, a 38-year old man who suffered paralysis from his chest down after being repeatedly stabbed in his back in 2010.  The knife attack left Darek with a completely severed spinal cord, leaving him with a mere thin strip of scar tissue on the right side of his spinal cord, and unable to walk.

Pre-stem cell treatment, Darek was paralysed for almost 2 years after the knife attack, with virtually no hope for recovery despite intensive physiotherapy.

Post-stem cell therapy, and in collaboration with UK scientists, Polish surgeons removed 1 of Darek’s 2 olfactory bulbs (used in the sense of smell) from his upper nasal cavity to make a culture of olfactory ensheathing cells and olfactory nerve fibroblasts.  After 2 weeks, the cells in this culture were directly transferred into his spinal cord (via 100 micro-injections, both above and below the injured site).

The olfactory bulb offers the greatest source of olfactory ensheathing cells.  Importantly, these olfactory ensheathing cells provide a pathway for the continual regeneration of the olfactory nerve fibres throughout adult life.

Nerve tissue was removed from Darek’s ankle (4 thin strips) and grafted into an 8mm gap on the left side of his spinal cord (to ‘bridge the gap‘ between the top and bottom of his severed spinal cord).

The researchers hypothesized that the transplanted (and regenerative) olfactory ensheathing cells can help nerve fibres to reconnect.  In other words, these olfactory ensheathing cells stimulated the spinal cord cells to regenerate/repair.  The ankle nerve tissue was auto-grafted into the 8 mm gap of the spinal cord, like a ‘bridge’.

There was nil risk of rejection of the ankle nerve tissue, olfactory ensheathing cells, nor olfactory nerve fibroblasts (as they were his own), hence no need for immunosuppressive drugs.

Darek took his first assisted steps 6 months after stem cell therapy.  Two years post-therapy, Darek is now able to walk with a walking frame.  He has improved trunk stability, partial recovery of voluntary leg movements, partial recovery of sensation, as well as increased muscle mass in, and improved vascular function of, the left leg (consistent with left-sided stem cell treatment).

MRI scans confirmed that the 8mm gap in the spinal cord was closed, post-stem cell therapy.

While moderately successful, walking with a walking frame is (quoting Darek) “an incredible feeling.  When you can’t feel almost half your body, you are helpless, but when it starts coming back it’s like you were born again.

Quoting Dr Tabakow, consultant neurosurgeon, It’s amazing to see how regeneration of the spinal cord, something that was thought impossible for many years, is becoming a reality.” 

Prof Geoff Raisman stated that this is “more impressive than man walking on the moon“.

Follow-up studies are needed before any final conclusions can be made.  It is hoped that 10 patients with comparable injuries can be similarly treated in the next year(s).

http://www.bbc.co.uk/news/health-29645760

The patient, Darek Fidyka, offers a small glimmer of hope and inspiration to many patients with spinal cord injury including Daniel Nicholls.  His father, David Nicholls, contributed generously to this ground-breaking research (via The Nicholls Spinal Injury Foundation), together with the UK Stem Cell Foundation.

Daniel Nicholls was only 18 on 30 December 2003 when he broke his neck and became paralysed from the neck down after diving into a wave and hitting a sandbank on Bondi Beach in Sydney, Australia (where I regularly swim and snorkel).

http://www.bbc.co.uk/news/health-29686709

QUESTION:

Many patients with spinal cord injury also suffer from nerve pain.  It would be interesting to find out if targeted stem cell therapy for spinal cord injury could also lead to reduced nerve pain in these patients.   

Until next week,

Sabina Walker, Blogger of Pain Matters blog

A journey of a thousand miles begins with a single step…..
(Lao-tzu, Chinese philosopher)

REFERENCES

(1) Tabakow et al. Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging. Cell Transplantation (21 Oct 2014).

doi: http://dx.doi.org/10.3727/096368914X685131

http://www.ncbi.nlm.nih.gov/pubmed/25338642

(2) Fergus Walsh. Paralysed man walks again after cell transplant.

BBC News Health (21 October 2014).

http://www.bbc.co.uk/news/health-29645760

http://www.bbc.co.uk/news/health-29686709

(3) Callaghan, Greg. Australian of the Year Alan Mackay-Sim on the advantage of being ‘an interested scientist’.

Sydney Morning Herald (Good Weekend) (8 April 2017): 18-21.

http://www.theage.com.au/good-weekend/australian-of-the-year-alan-mackaysim-on-the-advantage-of-being-an-interested-scientist-20170404-gvdcqe.html

Oxytocin for Migraine and Headache?

Dear Pain Matters blog readers,

Oxytocin is a natural hormone made by the hypothalamus and released by the posterior pituitary gland.  Nicknamed the ‘love hormone’, or the ‘cuddle hormone’, oxytocin helps induce labor (during childbirth), as well as promote lactation, maternal care, and couple bonding.

The word oxytocin is derived from Greek for quick birth (‘oksys’ = quick and ‘tokos’ = birth).

Oxytocin for Migraine and Headache?

Did you know that oxycontin may also relieve pain in some chronic migraine and headache sufferers?

Nasal-administration of oxytocin bypasses the Blood-Brain Barrier and directly activates the oxytocin receptors in the trigeminal nerve.  These oxytocin receptors are increased during inflammation.

In a study involving 40 chronic migraine sufferers, half were given a nasal oxytocin agent called ‘TI-001’, while the other half were given placebo.  This study reported that 4 hours after nasal oxytocin (‘TI-001’) treatment, 27% of the migraine sufferers had nil pain. 

Interestingly, nasal oxytocin (‘TI-001’) is most effective in the presence of pain-evoking inflammation.

‘TI-001’ is now being developed for chronic and long-lasting headaches, migraines, trigeminal neuralgia, and other chronic facial and head pains.

http://trigemina.com/category/press-releases/

http://trigemina.com/product-pipeline/

Oxytocin’s Effects on the Autonomic Nervous System

A study found that intranasal oxytocin spray was able to increase heart rate variability in healthy men during rest (compared to placebo) (Kemp et al, 2012).  

A study showed that oxytocin enhances parasympathetic activity without affecting the sympathetic nervous system (Gamer and Büchel, 2012).

Summary

In summary, nasal oxytocin leads to:

(1) Activation of the trigeminal nerve and reduced pain in some migraine sufferers; and

 (2) Increased heart rate variability due to increased parasympathetic (vagal) activity. 

For more information, please listen to Psychologist Kelly McGonigal’s 14-minute speech on stress and oxytocin’s role in modulating the stress response.  Note: While pain is not discussed, oxytocin is specifically discussed by Kelly McGonigal from 7:50 on:

How to make stress your friend

Here’s to oxytocin…..that may help reduce pain and suffering caused by chronic migraines, headaches, etc!

Sabina Walker

REFERENCES

OXYTOCIN’S POSSIBLE PAIN-RELIEVING EFFECTS ON CHRONIC MIGRAINES AND HEADACHES

(1) Megan Talkington; New Possibilities for Pain Treatment
7th Annual Pain Therapeutics Summit showcases therapies in development (20 Feb 2014).

http://www.painresearchforum.org/news/37432-new-possibilities-pain-treatment

(2) Yeomans et al; Abstract P59 Therapeutic Effect of Nasal Oxytocin in Chronic Migraine: Dependence on Cytokines (in ‘Abstracts of the 2013 International Headache Congress’); Cephalalgia (June 2013); 33(8 Supplement); pages 58-59.

(3) Yeomans; In the Pipeline: Nasal Oxytocin Explored for Migraines- Can migraine patients trust the “trust drug” to heal their pain? Practical Neurology (May/June 2013); 29-31.

http://practicalneurology.com/pdfs/PN0513_Pipeline.pdf

(4) Phillips et al; Relief of acute migraine headache with intravenous oxytocin: report of two cases. J Pain Palliat Care Pharmacother (2006); 20(3):25-8.

http://www.ncbi.nlm.nih.gov/pubmed/16931475

(5) Wang et al; The interaction between the oxytocin and pain modulation in headache patients. Neuropeptides (April 2013);47(2):93-7.

doi: 10.1016/j.npep.2012.12.003.

http://www.ncbi.nlm.nih.gov/pubmed/23375440

OXYTOCIN’S EFFECTS ON THE AUTONOMIC NERVOUS SYSTEM AND INFLAMMATION

(6) Kemp, Quintana, Kuhnert, Griffiths, Hickie, Guastalla; Oxytocin Increases Heart Rate Variability in Humans at Rest: Implications for Social Approach-Related Motivation and Capacity for Social Engagement; PLOS One (28 August, 2012); 7(8); e44014 (pages 1-6).

DOI: 10.1371/journal.pone.0044014

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0044014

(7) Gamer, Büchel; Oxytocin specifically enhances valence-dependent parasympathetic responses. Psychoneuroendocrinology (Jan 2012);37(1):87-93.

doi: 10.1016/j.psyneuen.2011.05.007. Epub 2011 Jun 8.

http://www.ncbi.nlm.nih.gov/pubmed/21641726

(8) Szeto et al; Oxytocin administration attenuates atherosclerosis and inflammation in Watanabe Heritable Hyperlipidemic rabbits; Psychoneuroendocrinology (May 2013); 38(5):685-93.

doi: 10.1016/j.psyneuen.2012.08.009.

http://www.ncbi.nlm.nih.gov/pubmed/22998949

Can Vagus Nerve Stimulation Decrease Inflammation, Hence Reduce Inflammatory Pain in Some Chronic Pain Patients?

Dear Pain Matters blog readers,

One of the most under-appreciated nerves of our body is the vagus nerve.  In Latin, the word ‘vagus nerve’ literally means ‘wandering nerve’.  (In fact, the words vagrant, vagabond, and vague are all based on the same word, ‘vagus’.)

So what does this vagus nerve do?

Answer:  Too much to answer in a single blog post, that’s for sure!

As such, I will only focus on one function of the vagus nerve (from an ‘inflammation/pain’ perspective).

Persistent localised inflammation is a key component of, and contributes to pain in, many chronic pain conditions including CRPS, rheumatoid arthritis (joint inflammation), and inflammatory bowel disease (Crohn’s disease, ulcerative colitis).

Dr Kevin Tracey’s research –

Dr Kevin Tracey’s team found that stimulation of the efferent vagus nerve (motor branch of the vagus nerve) can significantly curtail, and even block, the release of potentially damaging pro-inflammatory cytokines.  Not only can activation of the efferent vagus nerve protect against organ and tissue damage, but it may also reduce pain caused by inflammation.

Specifically, stimulation of the ‘Cholinergic Anti-Inflammatory Pathway’ including the efferent vagus nerve leads to decreased release of pro-inflammatory mediators including tumor necrosis factor alpha (TNF), hence reduced localised inflammation.

So what??  (you may ask)

In November 2012, Dr Kevin Tracey’s lab reported the first successful clinical trial that showed that stimulation of the vagus nerve can be effective for decreasing inflammation and pain in Rheumatoid Arthritis patients.

This is very exciting news….and it raises further questions….

For example, if stimulation of the vagus nerve can be effective in Rheumatoid Arthritis patients, could stimulation of this same vagus nerve also offer certain relief from inflammatory pain to other chronic pain patients with persistent localised inflammation (including some patients with CRPS, inflammatory bowel disease, etc)?

If yes, could vagus nerve stimulation be offered in addition to, or as an alternative to, current pain treatments?

I look forward to further updates of Kevin Tracey’s clinical study involving stimulation of the vagus nerve in Rheumatoid Arthritis patients.

Any benefits to Rheumatoid Arthritis patients may offer hope and inspiration to some chronic pain patients with persistent inflammation (eg CRPS, inflammatory bowel disease, etc).

Here’s to ‘less chronic pain, more gain’.

Sabina Walker

REFERENCES

Dr Kevin Tracey

(1)  http://www.feinsteininstitute.org/faculty/kevin-j-tracey-md/

(2)  “SetPoint Medical Presents Positive Clinical Results for First Human Study of Implantable Neuromodulation Device for Rheumatoid Arthritis” (12 Nov, 2012).

http://www.businesswire.com/news/home/20121112005932/en/SetPoint-Medical-Presents-Positive-Clinical-Results-Human#.VGQLh4fN6-I

(3A) The Body Electric

http://www.huffingtonpost.com/dr-kevin-j-tracey-md/the-body-electric_b_5396922.html

(3B) …Or click here for interview with Dr Kevin Tracey (if above link does not work):

Dr. Kevin Tracey Explains How A Nerve Stimulator Could Change Arthritis Treatment

http://www.huffingtonpost.com/2014/05/30/nerve-stimulator-arthritis-treatment_n_5420248.html

(4) Can the Nervous System Be Hacked?

By Michael Behar; 23 May, 2014; The New York Times (Magazine)

http://www.nytimes.com/2014/05/25/magazine/can-the-nervous-system-be-hacked.html

(5) Fox, Douglas. The Shock Tactics Set to Shake Up Immunology. Nature (04 May 2017); 545: 20–22.

doi: 10.1038/545020a

http://www.nature.com/polopoly_fs/1.21918!/menu/main/topColumns/topLeftColumn/pdf/545020a.pdf

Academic papers by Kevin J Tracey (there are now over 315 published papers):

(6) Koopman FA, Chavan SS, Miljko S, Grazio S, Sokolovic S, Schuurman PR, Mehta AD, Levine YA, Faltys M, Zitnik R, Tracey KJ, Tak PP. Vagus Nerve Stimulation Inhibits Cytokine Production And Attenuates Disease Severity In Rheumatoid Arthritis. PNAS (2016); 113(29): 8284-8289.

doi: 10.1073/pnas.1605635113

http://www.pnas.org/content/113/29/8284.abstract

(7) http://www.researchgate.net/profile/Kevin_Tracey/publications

Other References

(8) Bonaz B, Sinniger V, Hoffmann D, Clarençon D, Mathieu N, Dantzer C, Vercueil L, Picq C, Trocmé C, Faure P, Cracowski J-L, Pellissier S. (2016), Chronic Vagus Nerve Stimulation in Crohn’s Disease: A 6-Month Follow-Up Pilot Study. Neurogastroenterol Motil (2016); 28: 948–953.

doi: 10.1111/nmo.12792

https://www.ncbi.nlm.nih.gov/pubmed/26920654

(9) 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.

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

(Our 24-page Review Paper includes extensive discussion of Kevin Tracey’s research and whether this research may be relevant to CRPS.)  

 

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

Adverse Changes in the Brain Caused by Chronic Pain – Is this Reversible If Pain is Eliminated?

Dear Pain Matters blog readers,

It is now known that chronic pain (eg nerve pain) changes the brain.  This is true regardless whether the pain mechanisms are peripherally and/or centrally mediated.

Thus, regardless whether the pain mechanisms reside in the periphery (e.g. in a limb) and/or centrally (in the spinal cord/brain), the brain undergoes significant, adverse changes as a result of severe and persistent pain.  This is called pain-induced cortical reorganization.

The good news is that IF this nerve pain can be blocked, via Nerve Block, pain medicine, surgery, and/or another effective treatment, the brain can change back to normal.

Several studies show this including an important study by Birbaumer et al (1997) involving 6 Phantom Limb Pain patients.

Not only was Birbaumer’s team able to show that:

(1) severe, unrelieved nerve pain (Phantom Limb Pain) causes pain-induced changes in the brain,

(2) but they also showed that these brain changes were reversible,

but only in those patients who ‘experienced a virtual elimination of current phantom pain attributable to anesthesia (quoting from Abstract).   

In other words, the successful, pain-relieving effects of the Nerve Block (Regional Anaesthesia via Brachial Plexus Blockade) was simultaneously reflected by (quoting from Abstract)a very rapid elimination of cortical reorganization‘ in the brain in 3/6 patients.

The most impressive results were observed in a 56 year old patient with severe Phantom Limb Pain who lost his upper limb 28 years earlier.  This man (‘Subject Pr3‘) underwent both:

(1) reversal of pain-induced cortical reorganization; and

(2) complete elimination of Phantom Limb Pain

within only 20 minutes after complete anaesthesia in his stump and shoulder!

NB  It is likely that the pain mechanisms were peripherally mediated in the 3 patients who had pain relief from the Nerve Block.

In summary, the Nerve Block was effective for 3/6 patients with Phantom Limb Pain.  Thus, pain-induced brain changes were rapidly reversed as a direct consequence of the pain-relieving effects of the Nerve Block in these 3/6 patients.  However, this did not happen in the latter 3/6 who did not obtain relief from the Nerve Block.

Thus, the brain appears to change ‘for the worse’ to reflect persistent pain.  On the other hand, the brain is also able to change back to normal if/when persistent pain is finally successfully blocked.

ANOTHER PATIENT WITH PHANTOM LIMB PAIN (‘TREVOR’)

Here is another patient with Phantom Limb Pain named ‘Trevor’:

While Trevor suffered from severe Phantom Limb Pain prior to his Nerve Block, his residual pain is now managed, post-Nerve Block.  Quoting (go to 27:43 in the video link):

“….At that moment, it was instant pain relief for me.”

While this video does not show images of Trevor’s brain, I would bet 2 cents that Trevor’s brain also changed, both ‘before’ and ‘after’ his Nerve Block.

 

Here’s to less chronic pain in the world,

Sabina Walker

REFERENCES

(1) Birbaumer et al; Effects of regional anesthesia on phantom limb pain are mirrored in changes in cortical reorganization; J. Neurosci (1997); 17(14), 5503-5508.

http://www.jneurosci.org/content/17/14/5503.full.pdf