Category Archives: Lumbar Radicular Pain Including Severe Sciatica

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).


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).


(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).


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);


– 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



(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.

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

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

(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.


(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.

(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.

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


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

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

doi: 10.2174/0929867043363884.

(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.



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


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

Magnificent Conotoxins – Expanded (27 July 2014)

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

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



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

Dear Pain Matters blog readers,

Chronic Pain and Anti-TNF Drug Therapy

Infliximab and other selective anti-TNF drugs have been used to treat Lumbar Radicular Pain including severe Sciatica, Rheumatoid Arthritis, and Crohn’s disease (refer to first 8 papers in References)….and more recently, for Complex Regional Pain Syndrome (CRPS) (refer to all remaining References).


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

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

(1) Infliximab Treatment for 2 CRPS Patients –

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

– 1st Patient (Female, 50):  Chronic CRPS, Duration ~ 5 years

– 2nd Patient (Female, 55): Acute CRPS, Duration ~ 2 months, caused by left arm Colles’ fracture

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

More importantly (to the 2 patients anyway), there were:

– Reduced pain;

– Decreased vascular disturbances;

– Less swelling/edema;

– Enhanced motor function; and

– Improved symptoms (Huygen et al, 2004).

(2) Infliximab Treatment for 1 CRPS Patient –

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

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

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

(4) Perispinal Etanercept (A Back Pain Patient) –

The Institute of Neurological Recovery in Florida published an 8-minute YouTube on 25/11/2009 of a female patient with constant and severe back and leg pain for 2 years. Several minutes after a single dose of perispinal Etanercept, she enjoyed pain relief and leg movement.

‘Immediate relief after 2 years of severe constant pain 480p’


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

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

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


Wishing all pain patients less pain,

Sabina Walker



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

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

Ongoing trials are warranted including analysis of side effects.

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


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

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

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

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

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

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

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

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

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

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

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

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

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

DOI: 10.1111/papr.12078

(11B) Nederlands Trial Register 449 ISRCTN 75765780

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

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