Over the years many of our
clients have undergone spinal cord stimulation (SCS) and it’s now a
little over 7 years since we published the first of several articles on
this subject. At that time, although the technology had been available
for around 40 years, SCS remained a relatively novel procedure,
certainly in the UK. There was usually little or no choice of model –
you accepted what was on offer – and those that were offered were,
generally speaking, less effective than those available today.
Subsequently, two SCS veterans, Libby and Peter,
who each suffer Complex Regional Pain Syndrome in a lower limb, have
written to share their experiences. Interestingly, Peter’s stim is a
‘newer’ high frequency model, the Nevro Senza HF10.
A current client of ours, Paul, who underwent his original SCS
implantation some time ago, has recently had his low frequency stim
removed and a high frequency replacement has been recommended (see
High or low frequency?
So what exactly is the difference between high and low frequency stims?
Traditionally, stims have delivered their electrical impulses at low
frequencies, commonly 40 to 60 Hertz, for between 300 and 600
microseconds each. This results in paraesthesia, a sensation of
tingling, numbness, or sometimes even burning. The purpose of the
paraesthesia is to mask the pain. The effectiveness of low frequency
stims depends upon the accuracy of the overlap between pain and
paraesthesia, the idea being that paraesthesia is easier to endure than
On the other hand, high frequency stims, such as Peter’s HF10,
deliver impulses at a much higher frequency, usually around 10,000
Hertz, and the impulses are substantially shorter, typically around 30
microseconds. In most cases this results in the delivery of pain relief
with no corresponding paraesthesia.
Which is most effective for pain relief?
In terms of levels of pain relief, this is always subjective and, as
is to be expected, figures vary from study to study. Taking a common
example of low back pain, some studies report that the percentage
effectiveness of pain relief is as much as 30% greater for high
frequency stims – a stark difference. It should be stressed, however,
that other studies have found little or no difference between the two.
In a study reported in November 2016,
171 people suffering back and leg pain were randomly implanted with
either a high frequency (HF10) or low frequency stim. At two years
post-implantation, on average, significantly more people were still
experiencing pain relief with the high frequency stim (76.5% vs 49.3%
for back pain and 72.9% vs 49.3% for leg pain). Further, for both back
and leg pain the level of pain relief was on average significantly
greater with the high frequency stim (66.9% vs 41.1% for back pain and
65.1% vs 46% for leg pain).
The report’s authors, a number of whom, it should be noted, declared
current or past financial interests with stim manufacturers, concluded
“The advantages of HF10 therapy are anticipated to impact the
management of patients with chronic back and leg pain substantially, and
possibly other pain conditions. The superior and durable results
demonstrated in this study are anticipated to lead to improved long-term
cost effectiveness and payer acceptance, making this therapy broadly
available to patients suffering from chronic pain.”
In the case of our client, Paul, who suffers CRPS in his left foot
and ankle, following the original procedure he estimated that his low
frequency stim was providing around 30% pain relief, but as time went by
this reduced to the point where any benefit was, at best, negligible.
His pain consultant feels confident that there is “a very reasonable prospect of him achieving a good degree of pain relief”
with a high frequency stim, although for other health reasons it is not
immediately possible for him to undergo the second procedure.
Of course, even if the popularity of low frequency stims begins to wane, there remain other options to consider:
There are now MRI-friendly stims.
A client of ours with a history of recurrent spinal surgery has opted
recently for an MRI-friendly stim given the very high prospect of her
requiring further spinal imaging in the future.
There are times when stem cell
related therapies would seem to be the panacea for all ills, but could
stem cell therapy soon become commonplace in relieving the symptoms of
CRPS? As we discuss below, if you have the hard cash, there are already
private clinics offering the treatment.
San Francisco research
We have considered previously the work being undertaken at the
University of California, San Francisco, into using stem cells to
overcome the neurological effects of peripheral nerve damage, including
pain. Their method involves transplanting into the spinal cord, Cortical
GABAergic Precursor Cells, which are derived from stem cells.
In the words of their research lead, Professor Allan Basbaum, this study “is
revealing an entirely new perspective on the circuits that process the
injury messages that generate acute and persistent pain and on novel
approaches to therapy.”
Professor Basbaum describes neuropathic pain as “a disease”
of the central nervous system. Nerve damage causes pain and to alleviate
it, the nerve damage must be treated. Traditional drug therapies, he
says, often provide only a temporary benefit and usually go hand-in-hand
with side effects, which in themselves impact tremendously on a
person’s quality of life. In repairing nerve damage through stem cell
therapy, their approach is entirely different. Their research suggests
that following the transplanting of stem cell, neuropathic pain is
decreased without side effects.
In addition to CRPS, among those conditions which he believes may in
due course benefit from stem cell therapy are Trigeminal Neuralgia and
Multiple Sclerosis. However, whilst the results in San Francisco have
been encouraging, they have yet to reach the human trial stage.
“A female Registered Nurse presented to the our clinic with a
chief complaint of left lower extremity pain after suffering from a
complex, medial malleolar fracture that required operative repair and
internal fixation. Post-operatively she experienced allodynia and was
diagnosed with CRPS/RSD. Despite many months of aggressive therapy she
was still unable to ambulate with any weight bearing on the left leg. In
addition to using a knee scooter for mobility she had clear trophic
skin changes. Both vaso and sudomotor findings were present.
“As a result of the findings local injection including posterior
tibial nerve block, sciatic nerve block, lumbar epidural steroids, and
L5S1 facet region injections were tried. Blocks were followed with
proliferative injection into the medial deltoid and tibial-calcaneal
ligaments. Medication changes including the addition of clonidine to aid
in vasodilatation, non-narcotic analgesics, and muscle relaxers.
Nutritional recommendations were made and restorative therapy was
prescribed. Variable success was achieved.”
Following discussion, a decision was taken to proceed with stem cell
therapy. Cells were harvested from her hip and transplanted into her
calf, with a platelet rich plasma (PRP) booster given 30 days later. The
results were reported as follows:
“At two week follow up trophic skin changes already showed signs
of lessening. The patient had also begun to weight bear on the left leg
and reported less allodynia. By the time the 30 day PRP booster was
performed she was no longer using adaptive aids to walk however
compensatory gait persisted. Six weeks after the stem cell procedure
trophic skin changes, sudo and vasomotor instability, and allodynia had
Interestingly, a quick internet search reveals that a number of
private clinics have wasted no time in offering stem cell therapy for
CRPS, one of them citing this recent case study. Whilst, understandably,
this will be of huge interest to anybody suffering the torment of CRPS,
it must be remembered that, certainly as far as CRPS is concerned, stem
cell therapy remains a largely experimental treatment. There do not
seem to be any recognised treatment protocols in place.
Also, the facts available from the Pennsylvania case study indicate
that the subject’s CRPS had remained localised in the lower part of her
left leg. That does beg the question as to just how effective stem cell
therapy might prove to those whose CRPS has spread elsewhere in the
Clearly, there’s a great deal of optimism for stem cell therapy going
forward, but perhaps the outcome of more wide-ranging human clinical
trials is needed before it’s considered a mainstream ‘fix’ for CRPS.
Over recent decades smoking has
increasingly become the most high-profile medical bogeyman. Before they
can take a single and no doubt deeply satisfying drag, tobacco consumers
must now run the gauntlet of eye-watering prices, prophetical messages
of doom, explicit medical imagery and social ostracisation.
Twenty years ago the publicised danger was focused on a number of
heart and lung conditions and a handful of cancers. Nowadays, you don’t
have to dig too deep to discover that the list of conditions for which
smoking is an established risk factor has grown exponentially.
So what about CRPS? Is smoking a risk factor for developing the condition? And for those suffering CRPS, can smoking exacerbate the symptoms/spread?
Thirty years ago, based upon data collected between 1978 and 1985, a small-scale study encompassing only 53 patients was published. This concluded that “smoking is statistically linked to” CRPS, with 68% of those in the study diagnosed with CRPS being smokers.
However, as a substantially higher proportion of the population
smoked in those days, did coincidence simply skew the data?
Interestingly, subsequent studies
have failed to reproduce these results. Nevertheless, many in the
medical profession, including medical experts in litigation, continue to
list smoking as a risk factor, always citing this one, frankly
Whether or not smoking is a risk factor for developing CRPS, do
smokers suffering the condition fair more badly in terms of both their
symptoms and the risk of it spreading?
The one specific study on this issue
found no relationship between smoking and levels of pain in CRPS. The
only positive relationship found was a statistically higher pain-related anxiety score among those with CRPS Type 1 who both smoked and consumed caffeine.
With a dearth of available evidence, I decided to take a sounding
direct from a clinical CRPS researcher, who has asked not to be named.
“We actually have no data at all to suggest that stopping smoking
actually helps the condition. Stopping smoking does improve wound
healing which is independently impaired by CRPS. Therefore, it’s not a
good idea to smoke if you suffer from CRPS and are recovering from surgery.
However, whilst smoking carries a host of significant health risks of
which we are all aware, I cannot say that there is any evidence that
smokers with CRPS fair any more badly than non-smokers in terms of the
symptoms of CRPS or its spread.”
Of course, in the interest of their overall health smokers should be
encouraged to desist. That said, I have seen no persuasive evidence that
smoking is either a risk factor per se for CRPS or that smokers with
the condition fair more badly than non-smokers.
I though it might be of interest to leave the final words to a client of mine with CRPS, who is also a smoker:
“I only smoke about three a day now on average, sometime one or
two more particularly if I’m having a pain flare. That’s a hell of a lot
less than I smoked before I had CRPS. I’ve tried to kick it altogether
but when I do, on top of everything else, it just makes my stress go
through the roof. It really is my little stress reliever. Even my doctor
says he can understand that and has stopped nagging me to quit,
although I doubt he’d say it officially! It just helps me to cope. To be
honest, I really don’t care these days about all the risks of smoking.
When you suffer with CRPS, life can’t get much worse anyway.”
In two years of blogging about
anything and everything to do with living with CRPS, this is probably
the most exciting article I’ve ever written. Truly. This is news that
could potentially be life-changing for CRPS sufferers everywhere.
Some history first: almost exactly two years ago, I wrote about a new
CRPS treatment available in Italy that those doctors described as the cure for CRPS.
That article was hopeful, with a few caveats: there was little data out
there beyond the anecdotal to suggest that this drug really was as
effective as claimed, and crucially, the treatment was only available in
Italy and only accessible to those who could afford thousands of Euros
to pay for it.
Well, that’s not the case any more. Neridronate infusions are now
available, for free, in the UK as part of a large-scale clinical trial.
Read on to find out how you can get this treatment.
The major pharmaceutical company, Grünenthal, has now started its Phase III trial of neridronate for CRPS that was announced earlier this year.
Neridronate was given a Breakthrough Therapy Designation for CRPS back
in 2017 by the American Food and Drug Administration; this means that
neridronate is viewed as a potentially revolutionary treatment for this
formerly largely untreatable condition and therefore it’s been put on
the fast track for approval.
What does the initial stage of the trial involve for participants?
Everyone who signs up to the trial will initially be randomly
allocated to a group where they either receive a placebo or the real
medicine. No-one will know which group they’re in; not the patients nor
the doctors. This is so the researchers can ensure that reactions to the
medicine are genuine and not influenced by expectation.
Participants will then receive 4 infusions over 10 days of either
placebo or neridronate, where the medicine is administered through a
drip into a vein. These infusions will happen in a hospital or clinic
with constant monitoring from medical personnel. You’ll be asked to keep
a detailed diary of how you feel for six months afterwards, covering
pain levels and any other effects you may experience. You’ll be asked to
take supplements of Vitamin D and calcium too, as a precaution because
neridronate has an effect on bones, and you’ll be given paracetamol to
take after the first infusions as occasionally they can cause flu-like
symptoms, but these should pass fairly quickly.
What’s the next phase?
After six months, you’ll be reassessed and then may have the option
to have further infusions. This will likely happen if you’ve been given
the dummy medicine in phase 1, or if the doctors think you might benefit
from further neridronate infusions. What this means is that everyone
will have the chance to experience the real medicine, regardless of
whether you receive placebo in the first phase.
If you do go into this next phase, you’ll again receive 4 infusions
over 10 days, but these will definitely be of the real medicine. You’ll
once again need to keep a diary for the next six months to monitor the
effects. The experience of patients who’ve had the treatment in Italy
suggests that it may take as long as six months to start feeling the
benefits of the medicine, hence the long follow-up period. Don’t expect
that you’ll necessarily feel better overnight and don’t assume the
treatment has failed if you don’t quickly see a change in your pain
levels. Overall, participation in the trial is likely to take about 14
months so you need to be sure you can make that commitment.
This is the only piece of ‘bad’ news I have to impart: the trial is
only open to those who’ve had CRPS for less than two years. That means,
regardless of when you received a diagnosis, this trial is only open to
those who’ve had symptoms of CRPS for less than two years. Although this
is disappointing to anyone who’s suffered with the disease for longer
(like me), the rationale behind it is understandable; as many sufferers
would attest, the longer you have the condition, the more problems it
tends to cause, ranging from issues with the central nervous system to thyroid deficiency to problems with the eyes, bladder, bowel, heart
and other organs. This trial needs to understand if this treatment
works for pure, simple CRPS, unencumbered by other medical problems that
tend to arise after you’ve had CRPS for a while, and thus they’re
limiting participation to those who haven’t had it too long. Like I
said, disappointing but understandable.
Even if you don’t have a CRPS diagnosis…
Trial participants can have CRPS type 1 or 2 and they don’t even need
to have a confirmed diagnosis as yet; the trial locations can also
diagnose, so if you think you’ve developed CRPS within the last two
years, regardless of whether a doctor’s told you that’s correct, it’s
well worth getting in touch.
Are there are contraindications?
Women cannot get pregnant whilst using neridronate as it’s known to
cause birth defects, so if you’re planning a pregnancy anytime soon that
could rule you out. You have to have an average daily pain score of
more than 4 (not generally a problem for anyone with CRPS, sadly!) and
you must be taking no more than a morphine equivalent dose of 200mg
daily if you’re on an opioid painkiller. Your medications must be stable
and you’re asked to keep them that way during the trial. Throughout the
study you’ll have regular blood tests done and the infusion will be
given through a drip into your vein, so if you’re scared of needles that
might be problematic.
How do I find out more?
The UK trial is being headed up by a team from St Pancras Clinical Research in London. If you visit the linked page, you can fill in a short form and they’ll contact you to discuss the trial further.
Where is it taking place?
The trial is happening in 8 locations across the country: Liverpool,
Manchester, Barnsley, Cannock, Blackpool, Leeds, Stockton-on-Tees and
London. If you participate, then they’ll reimburse all reasonable travel
expenses and you don’t have to live locally; the St Pancras team in London, for example, stress that they’d be very happy to deal with trial participants from anywhere in the UK.
What about the rest of us?
Although it’s disappointing that those of us with longer-standing
CRPS can’t take part in the trial, I still think that overall this is
fantastic news. The truth is that this really may be the cure for CRPS;
the doctors I spoke to, whilst inevitably cautious, are very hopeful
that this may just be the case. And even though they’re limiting
participation, there’s still anecdotal evidence coming from Italy that
the treatment can be hugely beneficial to people who’ve had the illness
for a very long time.
This is the last clinical trial before the drug goes forward for
licensing, so if everything proceeds as hoped with the medicine in terms
of showing significant benefit to trial participants, we may only be a
few years away from this being available on the NHS. In a world where
all doctors can do for CRPS sufferers is attempt to manage the symptoms,
we are on the verge of having something that is truly a treatment for
this hateful illness. And that means that right now the future looks
brighter for every CRPS sufferer than it has done ever before. And
that’s amazing. Watch this space.
The word ‘sympathectomy’ has the ring of something lulling you into a false sense of security. It starts off well – ‘sympath’ – ok, it’s missing the ‘y’, yet still verging on the warm and comforting. But then you reach those final two syllables – ‘ectomy’ – yup, that means surgical removal.
So what exactly is a sympathectomy and can it be effective in reducing the pain of CRPS?
Fight or flight
It’s thought that Complex regional Pain Syndrome (CRPS) may be the
result of a problem in the sympathetic nervous system (SNS), which is
part of the autonomic nervous system.
The SNS is responsible for stimulating our ‘fight or flight’ response
– our body’s primitive, automatic, response that prepares us to ‘fight’
or ‘flee’ from a perceived threat to our survival. In response to a
stressor, the SNS triggers various physiological changes; increased
muscle blood flow and tension, dilated pupils, accelerated heart rate
and respiration, and increased perspiration and arterial blood pressure.
What is a sympathectomy?
A sympathectomy is an invasive procedure
that uses either a surgical or chemical approach to interrupt the SNS
with a view to increasing blood flow and thereby decreasing the pain of
CRPS and neuropathic pain. A chemical sympathectomy uses an injection of
either phenol or alcohol to interrupt the SNS by destroying sympathetic
nerve tissue. The surgical approach involves severing the sympathetic
A sympathectomy may be carried out near the top of the spine (a
cervico-thoracic sympathectomy) or near the bottom of the spine (a
Is there any evidence that they work?
In reality, there is exceedingly little good quality evidence on the
efficacy of sympathectomies as a treatment for CRPS and neuropathic
pain. Indeed, a Cochrane Review in 2013 could find “only one small study (20 participants) of good methodological quality”. The authors of that review concluded:
“The practice of surgical and chemical sympathectomy for
neuropathic pain and CRPS is based on very little high quality evidence.
Sympathectomy should be used cautiously in clinical practice, in
carefully selected patients, and probably only after failure of other
treatment options. In these circumstances, establishing a clinical
register of sympathectomy may help to inform treatment options on an
individual patient basis.”
The overriding suggestion seems to be that the success rate of
sympathectomy procedures are low and even where some benefit is
achieved, it is usually short-lived. And that’s without considering the
risk factors of the procedure itself, particularly for somebody
Despite these warnings, the highly worrying reality is that
sympathectomy and particularly chemical sypathectomy remains popular
with a few pain medicine consultants in the UK, both within the NHS and
privately. And despite the warnings above, I am aware from clients that
they are sometimes still offered as a treatment option in the early
stages of CRPS, not “only after failure of other treatment options.”
Clearly, anybody offered a sympathectomy for CRPS, particularly in
the early stages, needs to quiz their specialist closely on the
evidential basis for their recommendation. Certainly, in that situation
you cannot be criticised for seeking a second opinion.
It has long been accepted that
CRPS can spread from its initial presenting site to other (sometimes
remote) areas of the body. For most people with CRPS, the prospect of
their condition spreading is understandably their greatest fear.
The exact mechanism behind the spread of CRPS remains unclear but
there are two studies that have been published in the last 20 years
which purport to examine whether there is any obvious pattern to this
Before considering the results of these studies, it is worth taking a
moment to consider the types of terminology often used in describing
the spread of CRPS:
Contiguous Spread – refers to the (usually) gradual enlargement of
the area originally affected, commonly moving up the limb or body.
Contralateral or Mirror Image Spread – refers to the appearance of
symptoms on the opposite side of the body in an area closely matching
the location of the area originally affected.
Independent Spread – refers to the appearance of symptoms in an area
distant to and non-contiguous from the area originally affected.
Ipsilateral Spread – refers to spread on the same side of the body as the area originally affected.
Diagonal Spread – refers to the appearance of symptoms in the limb diagonally opposite to the one originally affected.
As mentioned above, there are principally two studies to consider.
However, identifying patterns between these studies is virtually
impossible. In addition to very small sample sizes, each study had
somewhat different objectives and criteria.
The results of the larger study
were published in the Journal of Neural Transmission in 2011 and
involved a retrospective study of 185 people with CRPS. However, this
study seems to have considered the spread of CRPS to other limbs only
and not contiguous spread or independent spread. The results were
summarised as follows:
“We set out to determine patterns of spread of CRPS and the
factors that are associated with spread. Our results show that CRPS
usually affects one limb but in some cases it spreads to another limb,
most often in a contralateral (53%) or ipsilateral (32%) pattern and
usually without secondary trauma. A diagonal pattern of spread was
nearly always triggered by a new trauma. Spontaneous spread and spread
after a separate trauma followed different patterns.”
Of interest, this study did identify that the “median interval between the occurrence in the first and second limb was 21 months.”
In a much smaller study published way back in 2000, 27 patients were studied retrospectively. It was reported that:
“Three patterns of spread were identified. ‘Contiguous spread
(CS)’ was noted in all 27 cases and was characterized by a gradual and
significant enlargement of the area affected initially. ‘Independent
spread (IS)’ was noted in 19 patients (70%)…’Mirror-image spread (MS)’
was noted in four patients (15%)…Only five patients (19%) suffered from
CS alone; 70% also had IS, 11% also had MS, and one patient had all
three kinds of spread.”
Can we learn anything useful from these studies?
The only areas where the studies overlap seems to be in relation to
mirror-image spread, but even there the percentage of those affected
differed wildly; 49% (2011) and 15% (2000). The sample size in both
studies was extremely low, particularly in the study published in 2000.
Perhaps that goes some little way to accounting for the considerable
disparity in those results.
Despite the tiny sample size of only 27, perhaps the two most worrying statistics appear in the results of the 2000 study:
“Contiguous spread was noted in all 27 cases and was characterized by a gradual and significant enlargement of the area affected initially” [my emphasis].
“Independent spread was noted in [70% of] patients”.
Even treating those figures with caution, for anybody with CRPS they will make terrifying reading.
Clearly, attaining a better understanding of both the nature and
mechanism of the spread of CRPS is hugely important. Identifying
patterns (if any) in that spread will be fundamental to achieving such
an understanding. A large scale, multi-centre study examining patterns
of spread is long overdue.
In an earlier article
we considered changes to the brain in people with CRPS solely in the
context of poor memory or ‘brain fog’. In this regard, in addition to
factors such as poor sleep and the side-effects of medication, there has
long been speculation in the medical profession that memory loss for
those suffering CRPS may also be the result of a malfunction in a part
of the brain known as the Limbic System, which is involved in the
control of our mood and instinct.
However, in recent years, more advanced medical imaging techniques
have meant that, for the first time, there is actually now visual
evidence that people with CRPS undergo significant changes in certain
areas of the brain.
The studies undertaken involve complex neuroscience, much of which
can be difficult to fathom. Before considering the results of these
studies further, a brief glossary may be helpful. My apologies to anyone
in the science community for the over-simplification, which is entirely
for my benefit!
Grey (or gray) and white matter
The brain essentially consists of grey matter and white matter, named
for their respective shades (actually pinkish-grey and white). The
shade comes down to the fat content and the presence of blood vessels.
Grey matter comprises neurons (commonly referred to as ‘brain cells’)
and glial cells, which hold neurons in place, insulate them from one
another, supply them with essential oxygen and nutrients and remove
White matter comprises the nerve fibres which connect areas of grey
matter and along which nerve signals pass. If an area of white matter is
damaged, the brain may eventually be able to rewire itself; finding an
alternative route to replace the lost connection(s).
Such rewiring is an example of brain plasticity. Brain plasticity (or
neuroplasticity) is the brain’s ability to change itself over time by
modifying its connections. These changes do not just occur in order to
repair damaged connections. They are essential to our development,
allowing us to develop from a child to an adult, as well as helping us
to adapt to new situations and environments.
But brain plasticity can also have a negative effect.
The researchers found that people newly diagnosed with CRPS showed
both reduced blood flow and a lower volume of grey matter in regions of
the brain associated with both pain and movement. This indicated the
occurrence of brain plasticity during the early stages of CRPS.
In patients with long term CRPS, whilst there did not appear to be a
further reduction in the volume of grey matter, the study found that
there was a clear negative relationship between average levels of pain
and the volume of grey matter in regions of the brain associated with
pain processing. In other words, the lower the volume of grey matter in
those areas, the higher the average levels of pain reported.
Graded Motor Imagery
However, the ability of the brain to change can provide hope in the
form of targeted therapy. Perhaps the best example of this familiar to
people with CRPS is Graded Motor Imagery (GMI).
The idea behind GMI is to train the brain to re-connect to the part
of the body affected by pain. The accepted theory is that in a person
with CRPS, their brain effectively disowns the part of the body
affected, seeing it instead as a threat. Normally, when we injure
ourselves the brain perceives this threat and, as a protection
mechanism, produces pain as an alarm signal, which allows us to deal
with and treat the injured area. However, in cases of CRPS, this alarm
system is faulty.
GMI focuses on the areas of the brain responsible for sensation and
movement. In each area there is a particular space for each part of the
body. When somebody suffers pain for a long time the space associated
with the painful part of the body can become ‘fuzzy’, creating confusion
in the brain, which in turn continues to produce pain as a protection
mechanism. In essence, this is the brain’s way of attempting to identify
the affected part of the body. GMI involves a series of steps aimed at
helping the brain to re-identify the affected part and thereby reduce
pain. The step in the GMI process that most people are familiar with is
of course mirror therapy.
Whilst there has been considerable research on the efficacy of GMI as
a treatment for CRPS, the results reported can at best be described as
variable. Interestingly, however, in terms of a reduction in levels of
pain, results for GMI have generally been more positive for people
suffering CRPS than for people suffering other chronic pain conditions.
As Libby Parfitt reported back in January 2018,
the multiple-centre trial of a seemingly promising drug for the
treatment of CRPS, Zoledronic Acid (also known as Zoledronate), was
halted by the pharmaceutical company, Axsome Therapeutics. The reason
given for this move was “futility”; in other words, the data collected to that point suggested that the trial was not going to meet its objectives.
As Libby said at the time: “It looked promising and many thought
we might finally be on the verge of a breakthrough in actually treating
CRPS as opposed to simply managing its symptoms.”
Zoldronate is a member of a family of drugs known as bisphosphonates
which, among other things, help prevent the loss of bone density and as
such are commonly used in the treatment of osteoporosis. Another
bisphosphonate, Neridronate, about which we have also written previously, is actively available in Italy for the treatment of CRPS.
In 2014, which of course was prior to the halting of the Zoledronate trial, a meta-analysis highlighted “that
bisphosphonates should be the pharmacological agents of choice in the
management of [CRPS Type I], given also the limited efficacy
demonstrated by other medications.”
Another member of the bisphosphonate family, Pamidronate, which more
often is used to treat secondary bone cancer, continues to be used to
also treat early stage CRPS.
As long ago as 2004, a small scale clinical trial concluded that “Pamidronate
may be a useful treatment option in the management of patients with
CRPS Type I. Although treatment response was variable, the majority of
patients improved. Early administration in tandem with other treatment
measures is recommended.”
In that trial it was noted that after 3 months there was an overall
improvement in both pain score and physical function compared to the
control group who were given a placebo. Despite these promising results,
since then there have been no larger scale clinical trials of
Pamidronate. However, in the UK, pain medicine consultants in some NHS
Trusts are now referring patients with early stage CRPS for a
Pamidronate infusion whilst maintaining their general regime of
medication and physical therapy. One CRPS sufferer we spoke to recently
had experienced some short term improvement in pain and function
following a Pamidronate infusion, but the treatment was not repeated.
Clearly, despite the apparent failure of Zoledronate, the medical
profession continue to have faith in bisphosphonates more generally as
an additional therapy for early stage CRPS. Interestingly, a study in 2001 expressed cautious optimism that Pamidronate may even be effective in the treatment of established CRPS, but stressed “these results need to be confirmed by a controlled placebo study.” As seems to be a common theme here, it does not appear as though such a further study has taken place.
The standard of clinical practice for most conditions varies from
country to country and this is certainly the case for Complex Regional
Pain Syndrome (CRPS). Indeed, in Europe there has long been a desire to
see a uniformity in approach to the diagnosis, treatment and management
of the condition.
What they claim to have produced is “17 standards of the
diagnosis and management of CRPS for use in Europe. These are considered
achievable for most countries, and aspirational for a minority of
countries depending on their healthcare resource and structures.”
Of these 17 standards, there are 4 in pain management, 3 each for
physical rehabilitation and care pathways, 2 each for diagnosis and
distress management and 1 each for assessment, multi-disciplinary care
Of course, these very much represent minimum standards.
Despite that, very few countries meet them already. For the majority,
the timescale for implementation is likely to be a lengthy one.
Agreement was not possible in all areas and they also concede that “research [is] needed to improve the validity and uptake of these standards”. However, at the very least they represent for the first time a benchmark for healthcare organisations at a national level.