Successful Treatment of Primary Erythromelalgia with Ziconotide (Prialt)

Dear Pain Matters blog readers,

Here is an interesting case:

Primary Erythromelalgia Treated with Intrathecal Ziconotide:

A 31-year old woman suffered from primary erythromelalgia for most of her life.  Symptoms included:

• Painful reddish skin and swelling in both feet and lower legs;
• Loss of vision in right eye and severely impaired vision in left eye (due to bilateral congenital glaucoma, exophthalmos/abnormally protruding eyeballs and megalocornea);
• Constant erythema and excessively warm lower legs;
• Severe pain including:
  • Intense burning throughout both the lower legs;
  • Allodynia near the perimalleolar regions in both ankles; and
  • Hyperalgesia in bilateral gastrocnemius and instep (arched part of feet).

Physical examination confirmed warmer skin temperatures in the lower legs, very strong burning pain (10/10, when lying very still) and swollen ankles.  The skin on her feet was thickened, red and ulcerated, due to her habit of immersing her feet in cold water as often as possible (as part of self-medication).  Refer to (a) in first photo.  

March 2010 –

After trying ‘almost everything’, a decision was made to trial and implant an intrathecal pump drug delivery system in March 2010.

A low titration schedule from 0.3 mcg/die to 1.2 mcg/die of ziconotide was commenced.  This resulted in complete resolution of both allodynia and hyperalgesia.

Dosage was increased to 1.8 mcg/die.

It is noteworthy that the severe swelling and oedema in both lower legs and feet was significantly improved after 1 week of ziconotide treatment.  Refer to (b) in first photo.

Source:   Russo et al, 2015

April 2013 (3 Years Later) –

In April 2013, the patient presented 4 days late for pump recharging.  This delay resulted in both legs and feet being swollen with burning pain.  Refer to (a) in below photo.  

Following (4-day-delayed) refill, her legs and feet were no longer swollen 2 days later, and there was nil burning pain 1 week later.  Refer to (b) in below photo.  

Source: Russo et al, 2015

Summary:

The woman no longer had to immerse her feet in cold water resulting in improved skin appearance.  She was able to rest in a bed now (instead of staying up in a chair for months).  Overall, ongoing intrathecal ziconotide treatment offered an improved quality of life for the patient.

Long-term use of intrathecal ziconotide does not lead to addiction or tolerance.

Mechanisms:

Ziconotide exerts its analgesic effects by potently and selectively blocking neuronal N-type voltage-sensitive calcium channels at the presynaptic level, hence inhibiting neurotransmitter release.

Conclusion:

It is promising to see that severe pain including burning pain, hyperalgesia and allodynia, as well as swelling, redness and excessive warmth of lower legs and feet in patients with primary erythromelalgia may be managed by intrathecal ziconotide treatment in some cases.

Sabina Walker

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

Galen, 130-200 C.E.

REFERENCE:

Russo R, Caroleo MC, Cione E, Perri M, Paparo MT, Russo A.

Dual Effect of Ziconotide in Primary Erythromelalgia.

Case Reports in Medicine (2015); Volume 2015, Article ID 592170, 4 pages.

doi:10.1155/2015/592170

https://www.hindawi.com/journals/crim/2015/592170/

 

 

 

 

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

 

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:

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 the ‘best 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/

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 al; Ziconotide 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 Ziconotide; J Pain Symp Man (Dec 2006); 32(6):509-11.

doi:10.1016/j.jpainsymman.2006.08.002

Click to access 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