Category Archives: Complex Regional Pain Syndrome (CRPS)

Let’s Talk To An Inspirational Young Canadian Woman, Paula Orecklin, About CRPS, Sativex, Physiotherapy and Neuroplasticity

Featured Image provided by Paula Orecklin.

Sativex

Sativex is a cannabis-based mouth spray that is used for nerve pain relief in various painful conditions including cancer, complex regional pain syndrome (CRPS) and multiple sclerosis (MS).  It may also reduce spasticity, muscle spasms and sleep disturbances in MS patients (similar to the benefits of medical cannabis).

For more on Sativex, please see my blog post called ‘Medical Cannabis (Medical Marijuana) And Nerve Pain’.

For information about a cannibinoid called cannabidiol (CBD), please go to my blog post called ‘Chronic Pain and Cannabidiol (CBD) – ‘Cannabis With the Fun Bit Taken Out:  

https://painmatters.wordpress.com/2018/04/06/cannabidiol-cbd-oil-for-severe-chronic-pain-including-arthritis-osteoarthritis-and-ankylosing-spondylitis-in-the-back

A CRPS Patient, Paula Orecklin 

You may remember Paula Orecklin from my older blog post called ‘CRPS Video On CRPS By PARC’ (26/10/14).

I recently invited Paula to share more of her inspiring story including her challenges with severe chronic pain and her positive experiences with Sativex, physiotherapy and neuroplasticity work.  Paula immediately replied:

“I like being able to do something positive with all of this pain. If this can help other patients, I’m all over it. Sharing my story, talking to other people…I have to make something good out of all of this pain, you know? And I do have a lot of experience, I guess.”

Paula Orecklin (29) from Winnipeg, Manitoba, Canada, has complex regional pain syndrome (CRPS) that involves constant, severe pain in her right knee and lower right leg as a result of twisting her right ankle back in 2001 when she was only 13 years old. Thereafter, Paula couldn’t even put her right foot to the floor without triggering one vicious blast of pain after another, leaving her bedridden and literally screaming in bed for the next 2 weeks. Following this tragic and life-altering event, Paula had to resort to crutches (and later on, canes) for mobility and due to excess pain. She was wheelchair-dependent for a few months during 2004 – 2005 (caused by ‘blowing out her left knee’) and also for 3 years from 2013 to 2015 (due to unbearable pain leading to monthly ER visits for half a year).

Quoting from Paula’s 2013 YouTube (pre-Sativex treatment):

‘…Every single second, I am in pain, from my knee down to my toes. On my right leg, all there is is pain…there is always solid pain from my knee down. On top of that pain, I have other kinds, all different forms [of pain]…stabbing, shooting, burning, visceral, aching, throbbing…This is with all of my medications…’

See YouTube called ‘Paula Orecklin – UNE Patient Case Study – April 4, 2013’:

https://www.youtube.com/watch?v=_aAVOCGW5ac

Following 3 years in a wheelchair due to severe pain, Paula was offered Sativex for the first time in 2015.  In 2016, thanks to Sativex (and other medications), the support of a fantastic physiotherapist and neuroplasticity work with an excellent pain psychologist, Paula was finally able to trade in her wheelchair and crutches for walking canes!

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Image provided by Paula Orecklin.

However, despite Sativex, Paula still has constant, severe pain every single second of her life. In her words:

[CRPS] still has all sorts of horrible kinds of pain [despite Sativex]. I can be doing well and suddenly ‘a giant poker’ has been stabbed through my leg. I was at a meeting on Saturday and in the middle of it, my foot set on fire. I’m always in pain and then on top of that, there are all sorts of different kinds of pain that come on extraordinarily suddenly. What I said in the video [3 – 4 years ago] is exactly what [still] happens today.’

Thus, while Sativex does not eliminate Paula’s base level of constant and severe pain nor her initial sudden pain attacks from occurring, it can block the repetitive flare cycles. By preventing these ongoing vicious pain cycles in 5 minutes, Sativex enabled Paula to finally undergo physiotherapy to improve her function and mobility. In Paula’s words:

“…Sativex is good at keeping the huge flare cycles down… I’m doing better functionally, so much better. But it doesn’t really work on my constant level of pain.”

Before Sativex, Paula suffered from out-of-control pain levels due to sudden and repetitive waves of pain spikes that would combine with her initial pain spike. One pain spike would lead to another pain spike, and on and on it went. This vicious and ongoing pain spike cycle often led to extremely high pain levels until finally her other medications kicked in.

Paula started using Sativex sublingual mouth spray 2 years ago. While it ‘tastes pretty disgusting, like spraying mosquito repellent into your mouth’, Paula said that she was doing very well as Sativex helps her manage her pain levels better. Being a mouth spray, Sativex has the advantage of gaining faster access directly into the blood capillaries via diffusion through the tissues under the tongue.

Paula has a prescription for a refill bottle of Sativex every 8 days. Sativex is not covered by public healthcare where Paula lives in Manitoba, and at CDN256.05 a bottle, Sativex is not cheap. Even though Paula’s private insurance helps defray most of the cost, Paula is still left out-of-pocket CDN60 per bottle. Using up to 12 sprays a day (and even up to 15 sprays on very painful days), a bottle of 90 sprays can go very quickly.

Despite its costs, Paula finds Sativex’s ability to block the repetitive flare cycles worthwhile. For the first time in her life, Paula has finally found a way to stop the vicious and ongoing cycles of pain spikes before they even start. This enables Paula to do physiotherapy and neuroplasticity training despite ongoing, unrelenting and severe pain. For example, she is now able walk between 1 to 2.4 miles with the aid of 2 walking canes.

Paula does not have any side effects from Sativex other than feeling ‘fuzzy everywhere’ on ‘really bad days’ when more than 9 – 10 sprays and increased hydromorph IR are required.

While Paula has tried medical marijuana (medical cannabis), she found it ineffective against her painful flare-ups. In contrast, Sativex is able to stop her pain flares in 5 minutes hence preventing a vicious circle of painful flare-ups. Furthermore, because Sativex looks like a regular inhaler, it is easier for Paula to be seen using Sativex than, say, medical marijuana. In other words, Sativex is not associated with the social stigma associated with using medical marijuana for pain management.

[I’ve gone from being] forced … to leave university, to carrying the Olympic torch [see photo below], to helping found a local CRPS support group, to creating my own Disability holiday….that after 15 years I …still [attend]. I’m going to celebrate it again this March…after 16 years I’m actually going somewhere now.  I’ve managed to make as much of a life out of my circumstances as I can.”

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Image provided by Paula Orecklin.

On behalf of all Canadians with chronic pain, Paula was formally honoured and selected to be an Olympic torchbearer for the 2010 Vancouver Olympic Winter Games. Paula had to practice walking and holding up one of her old crutches (in lieu of the Olympic torch) for 6 – 7 months beforehand.

One very early morning on a cold wintry day at -30C in January 2010 in Virden, Manitoba, Paula successfully fulfilled her pledge to carry the Olympic torch for 500 meters without mobility aids! Needless to say, being chosen as an Olympic torchbearer for the 2010 Winter Olympics to represent all Canadians living with chronic pain was one of Paula’s proudest achievements.

Thanks to a multi-disciplinary approach to CRPS that involved:

  • Sativex treatment;
  • Hydromorph IR and other conventional pain medication;
  • Physiotherapy;
  • Neuroplasticity work (with her pain psychologist); and
  • Various other pain strategies,

Sativex made a huge difference to Paula’s quality of life by opening the door for the first time to physiotherapy, regular exercise and neuroplasticity work, leading to a dramatic improvement in her CRPS symptoms including repetitive painful flares.

In her own words:

‘I’ve found in the past few months that not only have I been able to do more, be out and see people, exercise and still not fall apart, but I’ve also been increasing my tolerance to everything. I’ve actually been using less breakthrough medication, both Sativex and my hydromorph IR. I’m genuinely doing better. I think I’m down to about a bottle every 13 days right now.’

‘Without Sativex, I would never have been able to get to where I am today.

The neuroplasticity would have helped with my own depression due to pain and my understanding of pain and just generally improved my mental state.

But no real improvement physically would have been possible without Sativex.’

‘I’m doing better than I have in a very long time. Sativex is absolutely critical to this upswing. With Sativex, I can give myself medication with every flare of pain. It kicks in in only 5 minutes. The pain doesn’t have a chance to build on itself but is cut down quickly. I can also give myself another spray in 5 minutes if the pain keeps getting worse or doesn’t go down enough.

I can take up to 12 sprays a day and there aren’t really any side effects. I can get a kind of drugged feeling, but it’s not a high nor is it particularly strong. I have to be careful to spray under different parts of my tongue (ie sometimes my tongue’s left side, sometimes up front in the middle, sometimes on the right) so I don’t get wounds under my tongue. However I’ve never had a single one develop. It’ll sting a little when I’ve used a ton of sprays in one spot, but that’s just a reminder to be sure to move it around. And this might be of clinical significance since my skin is very delicate and develops wounds from my CRPS. ….

I mean, the drug is no magical cure, but it’s been absolutely essential to my progress. Without it, I might have gotten some psychological benefit from the neuroplasticity, but I definitely couldn’t be able to move any better. I’d never have ever been in a place where I could work with my physiotherapist. Before Sativex, I was in my wheelchair for nearly everything. I was finally able to walk again because of [Sativex].’

‘I’ve been working with an amazing physiotherapist since this spring. I was finally able to start walking, but was doing it so unevenly I was hurting my good side’s hip. She’s made a big impact on getting me moving.’

‘…I just came home from the gym, did really well I was powering around the track, listening to music, just … moving. And that kind of feels like a medical miracle. I was in such horrible shape for so long, and it just feels so good. And painful of course, but that’s just a given.’ 

‘I’m doing better now than I have in so many years … I’ve never in my life been able to have sustained progress like this.  I’m still disabled, and there are so many things I still can’t do, but that’s not really what I’m concerned with right now. I’m just happy to see where I am now.’ 

‘Sativex has been really important in my life over the past two years, but I just don’t want it to come off like it’s a … well, miracle. It isn’t. It’s made a massive impact on my life, but I’d say that my massive improvement over the past year is only a third down to the spray.’

Paula added, ‘None of anything would have been possible without hydromorphone IR, nor the rest of my medications. Nothing would be possible without my pain specialist at the pain clinic. It really has been a team effort, and that’s not even counting my other physicians, or the essential support network I have. My parents support me 100%, and that’s both emotional and financial. My mother, in particular, is my caregiver and is a huge part of my life. I’m very lucky to have friends who understand and care too. My best friend’s support over the years has meant so much to me too.’ 

‘Now none of those other things helps in the same ways Sativex does. Without it, I wouldn’t be able to move forward and make sustained progress for what is literally the first time in my life since hurting my leg. I’d never managed to go forward at all, ever; plateauing was all I could hope for. But I still feel like all of those other things are coming together to really help me in way that Sativex alone couldn’t. In fact, what’s really amazing is that I’m actually not using as much Sativex as I used to. Everything’s coming together much better than I ever could have expected. My leg is actually dealing with things better, not needing the same amount of as-needed medications. For the first time too, I’m actually finding other non-medicinal things like heat packs are actually helping. Before, it was just way worse when I didn’t have them, but it didn’t lower the pain exactly. So you can say it is kind of a holistic thing – but one that needed Sativex to open the door to it, if that makes sense…’

Having said all of the above, Paula emphasized:

‘[I am] actually never without pain … Sativex helps to stop the vicious circle of escalating pain cycles in 5 minutes.’

‘…I’m still in rough shape. But when that rough shape is so much better than the rougher shape I was in [before Sativex]…

‘[CRPS] is still incredibly disabling. But when you start so low, every few inches up makes a big difference.

Paula’s positive experience with Sativex may offer hope and inspiration to other pain patients to also add Sativex into their overall pain management therapy.

Thank you, Paula, for sharing your beautiful story with us! Despite living with constant, severe pain, your strength and inner beauty never cease to amaze me! People like you are the inspiration and main driving force behind this blog.

With positive thoughts coming your way from everywhere and everyone,

Sabina Walker

Blogger, Pain Matters

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Patching up Pain with a Lidocaine 5% Patch

Dear Pain Matters readers,

Treatment via a lidocaine 5% patch may offer significant pain relief for patients including cancer patients with focal nerve pain.

Specifically, patients with severe and localised nerve pain including one of the following painful conditions may benefit from a lidocaine 5% patch that topically delivers lidocaine:

  • Postherpetic neuralgia and herpes zoster (shingles);
  • Non-diabetic and diabetic peripheral neuropathy;
  • Trigeminal (orofacial) neuropathic pain;
  • Erythromelalgia;
  • Chronic low back pain (Hines et al, 2002);
  • Post-surgical neuropathic pain (e.g. following surgery for cancer or otherwise); and
  • Neuropathic pain directly attributable to cancer.

Lidocaine works by blocking sodium channels including Nav1.7 that underlie many nerve pain conditions (and other mechanisms).  The release of very small amounts of lidocaine transdermally via the patch ensures that motor and cardiac functions remain unaffected.

While topical lidocaine patches leads to pain relief in 29%-80% of treated patients, likely via small-fiber block, it is not clear why lidocaine patches may work better in some patients than in others (Krumova et al, 2012).

The topical lidocaine patch, measuring 10 cm X 14 cm, should only be applied on top of unbroken skin and where the pain is the greatest.  Patches should only be used by patients who are not allergic to local anaesthetics including lidocaine and who are not sensitive to the adhesive material itself.

The recommended maximum daily dose is 3 patches worn simultaneously for 12 hours at a time.  Since the lidocaine patch can only be worn for 12 hours at a time each day, other pain medications may be necessary, especially during sleep.

Lidocaine 5% Patch Treatment for Severe Chronic Pain – Successful Cases

Four Patients with Severe Low Back Pain

Four (4) patients aged 30 to 64 had successful lidocaine 5% patch treatment for severe low back pain as well as leg pain, foot pain (including CRPS, left foot) and/or neck pain.  Their pain included burning and stabbing nerve pain.  Specifically:

(1) A 53-year old woman had severe low back pain since a motor vehicle accident in July 2000.  She also endured right leg pain and some right foot numbness.  The patient said that the lidocaine 5% patch treatment ‘helped about 80%’.

(2) A 30-year old woman suffered low back pain, neck pain and right leg pain including burning and stabbing nerve pain.  She had a lifting and twisting injury in 1996.  The patient stated that her pain had dropped from ‘8’ to ‘5’ thanks to lidocaine 5% patch treatment.

(3) A 64-year old man suffered low back pain after a lifting injury in 1987.  He also suffered CRPS in his left lower leg and foot.  Lidocaine 5% patch treatment offered effective pain relief for his CRPS, left foot, and his painful lower back.  Furthermore, he was able to stop all other pain medication.

(4) A 50-year old woman suffered low back pain and right leg pain including aching and burning pain for 22 years.  Lidocaine 5% patch treatment offered effective pain relief.

There were no adverse effects resulting from lidocaine 5% patch treatment (Hines et al, 2002).   

A Young Patient With Episodic Erythromelalgia In Both Feet

A 15-year old Caucasian girl who suffered disabling pain during episodes of erythromelalgia in both feet derived complete pain relief almost immediately after applying lidocaine 5% patches to the top of both of her feet, both at rest and during almost normal levels of activity.  

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Post-lidocaine patch treatment, the young patient was able to run around the track at school, play soccer, return to her physical education class, march in the school band and walk around the shopping mall for almost an hour.  As long as she did not overdo her activities, she was able to obtain 100% relief during the 12 hours of lidocaine patch use, plus another 2-3 hours after patch removal.  The patient slept without the patches.

Whilst offering complete local pain relief and no side effects, the lidocaine patch was unable to prevent the other symptoms of erythromelalgia from occurring including bright red skin and over-heated feet following physical exertion.

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(Davis & Sandroni, 2002, including both images).

Two (2) Patients With Nerve Pain       

1st Patient – A 74-Year Old Female Patient With Herpes Zoster (Shingles)

Despite prompt treatment for a herpes zoster skin rash, a 74-year old woman developed stabbing and burning pain in her rash-affected area.  The patient was offered 2 lidocaine patches daily to cover the painful region.  Within 4 weeks treatment, the patient obtained 75% relief from pain caused by her herpes zoster skin rash.  Most of her systemic pain medications were stopped.

2nd Patient – A 56-Year Old Man With Severe Neuropathic Pain Syndrome Following Microsurgery For A Neuroma in Right Foot 

A 56-year old man suffered severe nerve pain shortly after microsurgery to his right foot due to an interdigital neuroma.  His painful symptoms included severe burning pain, mechanical hyperalgesia and allodynia, together with other symptoms.  As a result, he could no longer work, was unable to wear socks and shoes (only sandals) and withdrew from his family and friends.

After applying half of a lidocaine 5% patch daily onto his painful skin region, the patient reported positive results.  After 8 weeks of lidocaine patch treatment, the patient enjoyed an 80% reduction in overall pain levels and consequently returned to work.  There were no side effects and the patients was able to stop all other analgesics (Hans et al, 2010).

Trigeminal (Orofacial) Neuropathic Pain And Lidocaine Patch Treatment

A British study revealed that lidocaine 5% patch treatment led to improved pain levels in 12 of 14 trigeminal pain patients including oral surgery patients.  Nine (9) of the 12 patients were able to reduce or stop their intake of other pain medications.  Given that the majority (12/14) patients with trigeminal nerve pain benefited from lidocaine 5% patch treatment, further studies are warranted (Khawaja et al, 2013).

Cancer Patients And Lidocaine Patch Treatment

A large Australian study in a comprehensive cancer centre revealed that lidocaine 5% patch treatment had a ‘potent analgesic effect’ in 24 of 95 (25%) patients while another 23 patients (24%) reported a ‘partial effect’.  Given that almost half (47/95, or 49%) of all cancer patients with nerve pain benefited from lidocaine 5% patch treatment, further research is warranted (Fleming and O’Connor, 2009).

Current Study Involving Lidocaine Patch for Lower Limb Amputation Pain

A Belgium-based trial is currently recruiting up to 20 patients with pain following above- or below-knee amputation to assess the effectiveness of lidocaine patch treatment for peripherally-mediated phantom limb pain and/or stump scar hyperalgesia (Hatem, 2016).  Stay tuned for updates…

Summary

While lidocaine 5% patch treatment is expensive and there is a small risk of a skin rash, many patients with focal nerve pain obtain significant pain relief from the lidocaine 5% patch, a targeted peripheral analgesic that is non-addictive and safe for long-term use.  

Now that’s a good way to patch up pain!

Sabina Walker

Blogger, Pain Matters

REFERENCES

(1) Davis, Mark D P; Sandroni, Paola. Lidocaine Patch for Pain of Erythromelalgia; Arch Dermatol. Jan 2002;138(1):17-19

doi:10.1001/archderm.138.1.17

http://jamanetwork.com/journals/jamadermatology/fullarticle/478622

(2) Fleming JA, O’Connor BD.

Use of lidocaine patches for neuropathic pain in a comprehensive cancer centre.

(Utilisation des timbres de lidocaïne pour la douleur neuropathique dans un centre d’oncologie)

Pain Research & Management : The Journal of the Canadian Pain Society. 2009;14(5):381-388

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779156/#!po=28.7879

(3) Hans G, Robert D, Verhulst J, Vercauteren M. Lidocaine 5% patch for localized neuropathic pain: progress for the patient, a new approach for the physician. Clinical pharmacology : advances and applications. 2010;2:65-70

doi: 10.2147/CPAA.S9795

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262358/

(4) Hines R, Keaney D, Moskowitz MH, Prakken S. Use of Lidocaine Patch 5% for Chronic Low Back Pain: A Report of Four Cases. Pain Med 2002; 3 (4): 361-365

doi: 10.1046/j.1526-4637.2002.02051.x

https://academic.oup.com/painmedicine/article-lookup/doi/10.1046/j.1526-4637.2002.02051.x

(5) Khawaja N, Yilmaz Z, Renton T. Case studies illustrating the management of trigeminal neuropathic pain using topical 5% lidocaine plasters. British Journal of Pain. 2013;7(2):107-113.

doi:10.1177/2049463713483459

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590123/#!po=23.6842

(6) Hatem, Samar; A Trial of Lidocaine Patch for Lower Limb Amputation Pain (Trial ongoing since 2016); Brugmann University Hospital

https://clinicaltrials.gov/ct2/show/study/NCT02696720?view=results

(7) Krumova EK1, Zeller M, Westermann A, Maier C. Lidocaine patch (5%) produces a selective, but incomplete block of Aδ and C fibers. Pain. 2012 Feb;153(2):273-80.

doi: 10.1016/j.pain.2011.08.020.

https://www.ncbi.nlm.nih.gov/pubmed/21995882

(8) Devers A, Galer BS. Topical lidocaine patch relieves a variety of neuropathic pain conditions: an open-label study. Clin J Pain. 2000 Sep;16(3):205-8.

https://www.ncbi.nlm.nih.gov/pubmed/11014393

(9) Many Other Lidocaine Patch/Pain Studies Can Be Found Here:

http://www.druglib.com/druginfo/lidoderm/abstracts/

Ziconotide (Prialt) and Complex Regional Pain Syndrome – 2 Successful Cases

Dear Pain Matters blog readers,

Almost 2 years ago, I wrote a Blog Post called:

Ziconotide (Prialt) for Nerve Pain Including CRPS?

https://wordpress.com/post/painmatters.wordpress.com/344

Quoting from my older Blog Post:

“….Ziconotide for 7 CRPS Patients ….. 2 patients had complete pain relief and as such, discontinued Ziconotide treatment altogether…… (Kapural et al, 2009).”

I find it fascinating that intrathecal (IT) ziconotide treatment resulted in complete pain relief for these 2 patients.

It is worthwhile elaborating further on these 2 former CRPS1 patients here:

(1) Patient 1 –

A male patient (Patient # 1, 16 years old, male) had CRPS1 in both of his legs following an Achilles tendon tear 2 years earlier.  He suffered burning pain, hypersensitivity to touch/temperature changes and loss of proprioception in both feet.  Pain management treatments including lumbar sympathetic blockade and various oral medications were unsuccessful.  The patient used a wheelchair for mobility.

During a ziconotide trial, dosages were titrated from 2.4 mcg/d to 24 mcg/d over 3 months.  His VAS score reduced from 100 mm to 40 mm by the 4th month of the ziconotide trial, and he was able to upgrade from a wheelchair to a cane for mobility.

The patient underwent IT pump implantation, and dosages were titrated from 5 mcg/d to 7.5 mcg/d over a 7 month period (with some side effects that were treated).

During the 2nd year, ziconotide dosage was reduced to 4.5 mcg/d.  The patient was finally pain-free, and he was able to resume normal activities.

By the 3rd year, ziconotide dosage was further reduced to 1.2 mcg/d, and he stopped taking oral medications altogether.  The patient continued ziconotide treatment (ranging from 1.2 to 1.4 mcg/d) for another 4 years, and this enabled him to be pain-free and active.

Post-7 years ziconotide treatment, during which he remained pain-free, (quoting from page 299) ‘his IT pump was filled with normal saline in preparation for an explanation’ (Kapural et al, 2009).

(2) Patient 2 – 

A female patient (Patient # 2, 32 years old, female) had CRPS1 in both of her legs due to a fall 5 years earlier.  The patient suffered burning pain and hypersensitivity to touch/temperature changes, and she preferred to use a wheelchair for mobility.  Pain management treatments had failed her completely including multiple oral medications, lumbar sympathetic blockade and spinal cord stimulator, SCS (VAS score, 100 mm).

Following a successful ziconotide trial, she agreed to IT pump implantation.  Dosages were gradually titrated upwards from 10 mcg/d to 145.5 mcg/d over 2 years, with no adverse events.  The patient continued at this dosage of 145.5 mcg/d for another 6 years.

After 8 years of ziconotide treatment, the IT pump no longer worked.  While waiting for a new IT pump, the patient noticed that she no longer had any pain.  As such, she stopped taking systemic opioid medication.  She was also able to walk without an assistive device.  Her defective IT pump and SCS were surgically removed one month later.

A year following removal of her IT pump and SCS, the patient remained pain free (VAS score, 0 mm) and had returned to college (Kapural et al, 2009).

Summary:

Ziconotide treatment (via a spinally-implanted pump) can offer significant pain relief, and may even, at appropriate dosages, lead to full recovery from CRPS1 for selected CRPS patients.  

It is paramount that ziconotide be titrated to avoid serious side effects.  The importance of correct dosage was discussed at great length in an earlier Blog Post:

https://painmatters.wordpress.com/2015/08/07/ziconotide-prialt-user-reviews-is-dosage-an-issue/.

Sabina Walker

“Sedare dolorem divinum opus est”
“It is divine to alleviate pain”

Galen, 130-200 C.E.

PS For those of you who want to learn more about cone snails (that inspired medical research into ziconotide), here is a 2 – 3 minute YouTube called ‘Killer Cone Snails’.  

NB If you find aggressive animal behaviour disturbing, please refrain from watching this YouTube:

REFERENCES:

(1) Kapural L, Lokey K, Leong MS, Fiekowsky S, Stanton-Hicks M, Sapienza-Crawford AJ, Webster LR (2009)

Intrathecal Ziconotide for Complex Regional Pain Syndrome: Seven Case Reports.

Pain Practice (2009), 9: 296–303.

doi:10.1111/j.1533-2500.2009.00289.x

http://onlinelibrary.wiley.com/doi/10.1111/j.1533-2500.2009.00289.x/abstract;jsessionid=6C89A05D226657327BD3D4FEF4221488.f04t04

More on Intrathecal Delivery of Ziconotide –

(2) Palca, Joe

Snail Venom Yields Potent Painkiller, But Delivering The Drug Is Tricky

3 August 2015

http://www.npr.org/sections/health-shots/2015/08/03/428990755/snail-venom-yields-potent-painkiller-but-delivering-the-drug-is-tricky

 

Restoration of Tactile Performance in the Affected Hand via High-Frequency Repetitive Sensory Stimulation May Lead to Reduced Pain in some CRPS Patients

Dear Pain Matters blog readers,

Prof. Dr. Christoph Maier and team recently found that restoration of sensation (i.e. tactile performance) in the affected hand via high-frequency repetitive sensory stimulation (HF-rSS) may result in significantly decreased pain in patients with complex regional pain syndrome (CRPS).

Specifically, the Current Pain Intensity decreased by more than 30% in 4 of 16 CRPS patients who underwent HF-rSS of the CRPS-affected hand for 45 minutes a day for 5 consecutive days only.

Significantly improved tactile discrimination in the CRPS-affected hand also occurred in all 16 CRPS patients following HF-rSS intervention.

There were no medication changes in the 16 CRPS patients who had HF-rSS  intervention.

Univ.-Prof.-Dr.-med.-Christoph-Maier.jpg

Prof. Dr. Christoph Maier

Featured Image and Above Image:

Sources:  

http://bergmannsheil.bg-kliniken.de/behandlungsspektrum/anaesthesie-intensivmedizin-palliativmedizin-schmerzmedizin/schmerzmedizin.html

http://www.schmerzfreies-krankenhaus.de/kooperationspartner.html

The Study Including Results:

The study involved 20 CRPS patients, 16 who underwent HF-rSS treatment for 45 minutes a day for 5 consecutive days, while another 4 had low-frequency repetitive sensory stimulation.

Targeted electrical stimulation was applied to all the fingertips in the CRPS-affected hand by a custom-made hand pad.

Four (4) of 16 enjoyed significant pain reduction (more than 30% pain reduction) following HF-rSS treatment for 5 consecutive days.  

According to Table 1 in the study by Maier and his team, the following 4 patients had significantly reduced pain intensities immediately following HF-rSS treatment for 5 days (compared to their average pain levels, 4 weeks preceding this treatment):

  • Patient #2 (46 years, male; CRPS, right hand, duration = 5 months; fracture/surgery)
    • Average Pain (prior) = 7
    • Current Pain (after) = 0
  • Patient #8 (58 years, male; CRPS, left hand, duration = 4 months; surgery)
    • Average Pain (prior) = 6
    • Current Pain (after) = 1
  • Patient #9 (60 years, female; CRPS, left hand, duration = 2 months; fracture/surgery)
    • Average Pain (prior) = 10
    • Current Pain (after) = 1
  • Patient #15 (60 years, male; CRPS, right hand, duration = 8 months; fracture/surgery)
    • Average Pain (prior) = 9
    • Current Pain (after) = 2

The same Table 1 also listed 2 additional patients with significantly reduced pain following low-frequency repetitive sensory stimulation:

  • Patient #19 (58 years, female; CRPS, right hand, duration = 9 months; surgery)
    • Average Pain (prior) = 7
    • Current Pain (after) = 3
  • Patient #20 (58 years, male; CRPS, left hand, duration = 4 months; fracture/surgery)
    • Average Pain (prior) = 5
    • Current Pain (after) = 0

It is not known how long these pain reductions lasted.

Summary:

High-frequency repetitive sensory stimulation (HF-rSS) to all fingertips in the CRPS-affected hand:

  • to improve sensory loss (i.e. restore sensation including tactile performance); and/or
  • to reduce pain in the CRPS-affected hand

may be a useful non-pharmacological (add-on) treatment for some CRPS sufferers.

Maier and his colleagues conceded that while CRPS patients were only tested for 5 consecutive days, greater pain reductions for more CRPS patients may have resulted had the testing period been significantly longer.

This is a fair comment given that a study involving 2 amputees with phantom limb pain resulted in restoration of sensation as well as nil phantom limb pain following ‘prosthetic system treatment’ for (up to) 2 years.

https://painmatters.wordpress.com/2016/08/11/restoration-of-sensation-may-lead-to-reduced-phantom-limb-pain-in-amputees/

Sabina Walker

“Sedare dolorem divinum opus est”
“It is divine to alleviate pain”

Galen, 130-200 C.E.

REFERENCE

(1) David M, Dinse HR, Mainka T, Tegenthoff M, Maier C.

High-Frequency Repetitive Sensory Stimulation as Intervention to Improve Sensory Loss in Patients with Complex Regional Pain Syndrome I.

Frontiers in Neurology. 2015;6:242.

doi:10.3389/fneur.2015.00242.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648023/pdf/fneur-06-00242.pdf

(2) High Frequency Stimulation in Pain Medicine

Kalus, Annegret

Ruhr-University Bochum (No. 163 – 20.11.2015)

http://aktuell.ruhr-uni-bochum.de/pm2015/pm00163.html.en

(3) Hochfrequente Stimulation Hilft Menschen Mit Schmerzsyndrom

Schubert, Christine

CRPS Bayern Morbus Sudeck Selbsthilfegruppe (19.2.2016)

https://by.crps-netzwerk.org/cms/blog/2016/02/19/hochfrequente-stimulation-hilft-menschen-mit-schmerzsyndrom/

Ziconotide (Prialt) User Reviews – The Fine Line Between Maximizing Pain Relief and Minimizing Severe Adverse Effects

Source of Featured Image:

https://en.wikipedia.org/wiki/Conus_magus

Dear Pain Matters blog readers,

Many nerve pain sufferers say they have tried EVERYTHING, to no avail.

The good news is that some patients with severe, intractable nerve pain obtain pain relief following Ziconotide (Prialt) treatment (while, sadly, others don’t).

Ziconotide (Prialt) is synthesized based on the venom of a marine snail called Conus magus.

For further details on Ziconotide (Prialt), please refer to literature including a paper by McGivern (2007).  You are also welcome to go to my earlier blog post, here:

https://painmatters.wordpress.com/2014/11/10/ziconotide-prialt-for-nerve-pain-including-crps/

BRIEF ANALYSIS OF ‘PRIALT USER REVIEWS’

An internet site called ‘Prialt User Reviews’ offers a collection of patient reviews:

http://www.rxlist.com/script/main/rxlist_view_comments.asp?drug=prialt&questionid=fdb92576_pem

The ‘Prialt User Reviews’  show that Prialt treatment may be a ‘hit-or-miss’ treatment for many patients with severe nerve pain.  Thus, while some severe nerve pain sufferers obtained significant pain relief from Prialt (that outweighed its side effects), many others were worse off due to Prialt’s severe side effects.

SOME POSITIVE ‘PRIALT USER REVIEWS’ 

A patient with low back pain commented:

“I did not realise how much this new drug helped me until I had to come off of it for a short period of time.”

Another pain patient wrote:

“I developed a BAD reaction to this med, even though it worked great for my pain.  Now I have all kinds of allergies and having trouble finding a med that is as effective without side effects.

A pain patient with 2 spinal operations wrote:

“Since I’ve had the pump, the pain is no longer in my legs.  I will be ever thankful to that little snail and its ooze.  God bless researchers.” 

A patient with chronic pain for over 10 years had a positive experience with Prialt.  In her own words, “…since I have been on these meds, things have turned around for the good….I thank God every day that I have my life back….”

Another pain patient stated:

“This for me has been a “life changing” positive experience.  I have been on the drug well over six years with NO side effects whatsoever….This has changed my life for the better as I am now able to do volunteer work…I had my occipital nerves sectioned as well as steroid-induced osteoporosis, so totally endorse this drug for neuropathic pain.”

A cancer survivor with chronic pain stated:

“My pain was due to cancer which is now in remission.  My first pain clinic pushed me too hard to increase Prialt and side effects were bad!  I heard music and it felt like my teeth were melting!  I kept reducing my Prialt until it was mixed w/a narcotic and that combination made my pain level from a constant 9 … to a livable 5-7!  This is the lowest my pain level has been in 9 yrs! … I am finally pleased with my Prialt and my Life.  After 8 years of trying different combinations and Prialt Levels and 1 pump reposition and 1 pump replacement, I am finally able to Live.  I can meet my husband for lunch most days ….Yes, it took several years to get the level just right and the side effects lower, but it was totally worth it to finally have a more normal and happy life!”

SOME NEGATIVE ‘PRIALT USER REVIEWS’ 

A patient with CRPS (RSD) for 8 years stated that Prialt is thebest at relieving pain BUT it’s not worth the side effects I get….several bad experiences and I always stuck it out since the relief was so good.  It’s no longer worth it.  I have no life, hardly leave the house and spend most of the time talking to myself’.

A former user said This medicine did help my nerve pain (moderately) but the memory loss is horrible.  I lost 50 lbs in 6 months.  I can’t concentrate well, agitated, no motivation, have extreme anxiety……I started having a pungent perfumey-like smell constantly, which started to become an obsession…..led up to a full blown manic episode …no sleep….thoughts of not wanting to live anymore….border-line psychosis….I’ve been off this medication for over 2 weeks now but still suffer from some of these side effects…..”

A pain patient who unsuccessfully underwent a Prialt trial wrote:

“…I started an IT pump trial with Prialt…..and the med was increased slowly (started out with about 4 mcg/day.  Increased eventually to about 7 mcg/day).  With the first increase, my pain improved (decreased).  With each successive increase of Prialt, my pain increased and so did side effects.  I became extremely dizzy, nauseated (with vomiting), confused, lethargic, my vision blurred, and I was unable to do anything but lie in bed and wonder what Prialt was doing to my brain…..”

IS DOSAGE AN ISSUE?

I find it very interesting that nerve pain levels did improve in several patients following Prialt treatment, despite severe side effects (see above).

Is it possible that the intrathecally-administered (spinally-administered) dosages were simply too high for those who suffered severe side effects, post-Prialt treatment?

Would nerve pain patients benefit from lower Prialt dosages for longer periods (before deciding to increase dosages)?  

Consider this example:

A 59-year old female with severe pain due to chronic trigeminal neuralgia (TN) pain underwent a single-shot trial of intrathecal ziconotide.  To reduce any adverse effects, the ziconotide dosage was intentionally kept very low, at only 1 mcg.  The patient’s TN pain levels dropped from ‘9’ to ‘6’ (that, unfortunately, returned to her original pain levels of ‘9’, 4 hours-post-ziconotide).  As such, 1 mcg/day ziconotide was added to her intrathecal combination of morphine and clonidine.  At this low dosage, the patient reported significant relief from TN, and (importantly!) no side effects (Michiels et al, 2011).

According to Webster (2005), to minimise adverse effects while also maximising pain relief, initial dosages must be very low and titrated very slowly.  Thus, for many patients, there is a fine balance between minimal adverse effects and maximal pain relief (Webster, 2005).

Ongoing studies are warranted to ascertain why Prialt treatment offers pain relief (with minimal side effects) for some nerve pain patients, but not for others.

Many patients had to stop using Prialt due to extreme, horrific, and intolerable side effects that included severe mental impairment, psychosis, personality changes, memory loss, hallucinations, minor to severe swelling of joints, tremors, paranoia, pain, bad mood swings, problems with sleeping, hearing loud music 24/7, confusion, anxiety attacks, depression, suicide risk, severe sinus infection, slurring speech, severe neurological symptoms, vision problems, severe weight loss, burning skin/electric shock sensations and allergies.  NB It is not clear whether some of the aforementioned side effects were solely caused by Prialt and/or due to other unknown factors.  Further studies of Prialt’s side effects are warranted.

Many studies into other novel drugs are underway (more later).

Wishing all pain patients less suffering and more hope.

Sabina Walker

PS  Please read the entire Prialt Patient Information Including Side Effects sheet before deciding to use Prialt.

http://www.rxlist.com/prialt-drug/patient-images-side-effects.htm

Also (quoting):

“Patient Comments are not a substitute for professional medical advice, diagnosis, or treatment…..”

http://www.rxlist.com/script/main/rxlist_view_comments.asp?drug=prialt&questionid=fdb92576_pem

PPS  It is important to note that not all Prialt users will offer feedback (positive or otherwise).  Furthermore, human nature tends to focus on the negative, rather than on the positive.  It is possible that many who obtain pain relief from Prialt choose not to post comments, while others who suffered severe side effects due to Prialt may offer feedback (to help others).

REFERENCES

(1) McGivern; Ziconotide: a review of its pharmacology and use in the treatment of pain; Neuropsychiatr Dis Treat. 2007; 3(1): 69–85.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654521/

(2) RxList – The Internet Drug Index

Prialt User Reviews

http://www.rxlist.com/script/main/rxlist_view_comments.asp?drug=prialt&questionid=fdb92576_pem

(3) For more information on Prialt, please refer to:

http://www.rxlist.com/prialt-drug/consumer-uses.htm

http://www.rxlist.com/prialt-drug/patient-images-side-effects.htm

http://www.prialt.com

(4) Michiels et al; Trigeminal neuralgia relief with intrathecal ziconotide; Clin J Pain 2011; 27:352-354.

http://www.researchgate.net/publication/51052321_Trigeminal_neuralgia_relief_with_intrathecal_ziconotide

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

http://rsds.org/ziconotide-in-complex-regional-pain-syndrome/

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