UK

CRPS and Smoking

Smoking
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July 10th 2018 | article by Richard Lowes

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.

CRPS

So what about CRPS? Is smoking a risk factor for developing the condition? And for those suffering CRPS, can smoking exacerbate the symptoms/spread?

Risk Factor

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 unsatisfactory, study.

Exacerbation

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. They said:

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.

Final words

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.

Source: article published with permission of BLB Solicitors

Potential CRPS cure now available in the UK

Pamidronate
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July 10th 2018 | article by Richard Lowes

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.

What’s happening?

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.

Who’s eligible?

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.

Source: article published with permission of BLB Solicitors

What is a sympathectomy and can it reduce the pain of CRPS?

Sympathectomy
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July 10th 2018 | article by Richard Lowes

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 nerve chain.

A sympathectomy may be carried out near the top of the spine (a cervico-thoracic sympathectomy) or near the bottom of the spine (a lumbar sympathectomy).

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.

Further, in one often cited article by Drs Hooshmand and Phillips, the warnings are even starker:

Complex Regional Pain Syndrome (CRPS) patients should not be exposed to aggravation of pain due to sympathectomy, chemical sympathectomy or radiofrequency sympathectomy.

and

Surgical procedures have no place in treatment of CRPS.

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 suffering CRPS.

Popularity

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.

This also seems entirely at odds with the new Royal College of Physicians UK “guidelines for diagnosis, referral and management in primary and secondary care” for CRPS which, tellingly, are silent with regard to the use of sympathectomy.

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.

Source: article published with permission of BLB Solicitors

How does CRPS spread and is there a pattern?

Patterns
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July 10th 2018 | article by Richard Lowes

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 spread.

Terminology

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.

Studies

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.

Source: article published with permission of BLB Solicitors

Evidence of brain changes in people suffering CRPS

Amygalda
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July 10th 2018 | article by Richard Lowes

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 science

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 waste.

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).

Brain plasticity

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.

CRPS

Research published recently in the Journal of Pain is just the latest to suggest that people with CRPS undergo significant brain plasticity resulting in marked structural and functional changes in certain areas of the brain.

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.

Source: article published with permission of BLB Solicitors

Keeping faith in bisphosphonates: Pamidronate for CRPS

Pamidronate
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July 10th 2018 | article by Richard Lowes

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.

Bisphosphonates

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.

Pamidronate

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.

Source: article published with permission of BLB Solicitors

Report of European Pain Federation task force on CRPS published

Europe
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Jan 13th 2019 | article by Richard Lowes

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.

With that in mind, this week saw the publication of a paper, “Standards for the diagnosis and management of Complex Regional Pain Syndrome: results of a European Pain Federation task force”. The task force was formed from some of the leading clinical researchers across the continent including, from the UK, Dr Andreas Goebel of the University of Liverpool. They were challenged to “produce mandatory quality standards worded as grammatically imperative (must‐do) statements.” In other words, to be as clear and unambiguous as possible.

Have they succeeded?

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 and information/education.

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.

In the UK, in 2018 the Royal College of Physicians published their own new and detailed guidelines on the diagnosis and management of CRPS.

Source: article published with permission of BLB Solicitors

Vitamins and supplements for Chronic Pain

Vitamins
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Feb 11th 2019 | article by Richard Lowes

Quite rightly, the first port of call for most people suffering chronic pain in any of its many guises are mainstream treatments and medications. However, many sufferers, particularly those whose chronic pain condition has become well-established and possibly resistant to therapy, turn for some symptomatic relief to certain vitamins and other supplements. This is usually as an adjunct (add-on) therapy rather than as a primary treament. Although viewed with a healthy degree of scepticism in some quarters, there is in fact scientific evidence supporting the benefit of some supplements.

Those set out below do not form a complete list and the benefit or otherwise of some is the matter of (in some instances considerable) scientific debate.

If you are considering taking any vitamins or supplements you are strongly recommended to discuss their possible efficacy or otherwise with your doctor before taking them. This is particularly important as even seemingly innocuous supplements may in fact interfere negatively with the action of your prescription and/or other mainstream medication.

Vitamins B9 (Folic Acid) and B12

Folic acid, which is also known as vitamin B9 or folate, is most commonly associated with pregnant women, who take it as a supplement during pregnancy to reduce the risk of birth defects in the developing child.

Vitamin B12 plays an important role in ensuring the normal function of the brain and the nervous system.

It has long been known that folic acid and vitamin B12 can boost the function of our immune system and are important for our overall health. However, research has shown that taking folic acid in conjunction with vitamin B12 can improve the symptoms of those suffering Fibromyalgia (FM) and Chronic Fatigue Syndrome (CFS or ME).

The vast majority of people diagnosed with ME suffer widespread and persistent pain. Similarly, people suffering FM have many symptoms common to those suffering ME and it is not uncommon to be diagnosed with both conditions concurrently. For this reason, much of the more recent research into FM has explored the role of central sensitisation, which may underlie a host of chronic pain conditions and suggests that ME and FM are simply different manifestations of the same underlying problem.

In fact, research has demonstrated that the benefits of taking folic acid in conjunction with vitamin B12 were particularly beneficial to those diagnosed as suffering both ME and FM. It was also found that higher doses of these supplements led to a greater reduction in symptoms.

But…

It was also found that those who took folic acid and vitamin B12 in addition to daily doses of certain medications such as Duloxetine, Pregabalin and opiate-based painkillers, benefitted less from taking the supplements. Despite that, doctors treating both ME and FM are increasingly exploring with their patients ways of incorporating these supplements into their daily medication regime.

Vitamin B complex

Research has shown the potential role of vitamin B complex as an additional therapy for those taking nonsteroidal anti-inflammatory drugs (NSAIDs) such as Ibuprofen, Naproxen and Aspirin for low back pain.

Vitamin B complex is a cocktail of B vitamins defined as 1 mg of vitamin B12, 50 to 100 mg of vitamin B1 and 50 to 100 mg of vitamin B6. Its addition to an NSAID drug regime seems to intensify the pain-relieving effect of the NSAID(s), although the exact reason for this is the subject of some debate.

Vitamin C

We have considered in an earlier article the role that vitamin C, also known as ascorbic acid, may play as a Complex Regional Pain Syndrome (CRPS)-preventative following limb fractures or limb surgery. As a result of a considerable amount of research, it is now widely accepted among the medical profession that there is at least some correlation between taking vitamin C and the chance of developing CRPS following limb fractures or limb surgery. In one study, 2.4% of the group taking vitamin C developed CRPS compared to 10.1% taking a placebo.

These results were replicated in another study where 1.7% of the group taking vitamin C developed CRPS compared to 9.6% of the placebo group.

Whilst a subsequent analysis of these results has cast some doubt over their reliability of both studies, as vitamin C is both inexpensive and safe, the advice received by most people following limb fracture or surgery is to take 500 mg of vitamin C daily for at least 50 days.

There are also conflicting studies as to whether vitamin C can help to reduce levels of pain in people suffering other chronic pain conditions such as arthritis.

Vitamin D

Whilst there is no conclusive evidence that taking vitamin D supplements can help to relieve chronic pain, it has been established that for reasons which are not fully understood, levels of vitamin D in people suffering a variety of chronic pain conditions are lower than in those not suffering chronic pain. For this reason, as maintaining levels of levels of vitamin D is vital to our health, supplements have been recommended to some people suffering chronic pain.

Magnesium

Back in 2009, research published into the use of intravenous magnesium as a treatment for CRPS Type 1, concluded that “The results of this pilot study show significant benefits of intravenous magnesium treatment on complaints and quality of life in CRPS 1 patients. Pain reported by patients was significantly decreased.

For most participants in that study the reported reduction in pain seemed startling, occurring within 20 to 30 minutes, with levels of pain remaining “significantly reduced” for up to 12 weeks. Participants also reported reductions in levels of hyperalgesia and allodynia. Researchers thought that magnesium was acting as a NMDA receptor antagonist, in a very similar way to intravenous ketamine.

Despite those promising results, a further study published in 2013 concluded that “Administration of the…[NMDA] receptor antagonist magnesium in chronic CRPS provides insufficient benefit over placebo.

This trial did not write off magnesium entirely, but recommended that any further research on magnesium for CRPS Type 1 should be limited to the acute phase only.

A classic example of hope to despondency following one research paper. Or is it?

Certainly in the UK magnesium, intravenous or otherwise, does not form part of the mainstream treatment portfolio for CRPS Type 1. There are, however, numerous anecdotal accounts to be found online of people with CRPS embracing magnesium in a variety of forms – intravenous, supplement tablets, topically-applied oil and magnesium flakes for foot baths.

Of course, the scientists will say that any benefit experienced may be down to chance or even the placebo effect and they may well be correct. However, what magnesium does have in its favour is that, in whatever form it’s taken, not only is it relatively inexpensive but, if the recommended dose is not exceeded, it is reasonably safe – certainly a lot safer than Ketamine!

Fish oil

There is evidence that certain types of chronic pain can be eased by consuming omega-3 essential fatty acids. Omega-3s, are often referred to as ‘fish oil’ as this is their main source.

The two most important types of omega-3 fatty acids found in fish oil are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which convert into compounds that reduce inflammation within the body. It is this anti-inflammatory action that is responsible for reducing pain. In one study, people dependant on NSAIDs for pain relief for chronic non-specific neck or back pain were able to reduce or even dispense entirely with those drugs after taking 1,200 to 2,400 milligrams of omega-3 daily as a supplement. This is very roughly the same amount of omega-3 found in a 125 gram serving of salmon, but of course supplements work out considerably cheaper!

Bromelain

Bromelain is an enzyme which comes from the pineapple plant. It appears to have anti-inflammatory and pain relieving properties, particularly in osteoarthritis and knee pain. However, considerably more research is required.

Conclusion

As the name makes clear, ‘supplements’ should only be consumed in addition to, not in place of, a healthy and well-balanced diet, including our proverbial 5-a-day. Over and above that it is apparent that some vitamins and other supplements can have a role to play in the long-term management of a variety of chronic pain conditions, particularly if they can help to reduce a person’s overall medication intake.

Fortunately, in recent years the medical profession have become a little more open-minded than once they were to the possibility of using certain supplements as an adjunct therapy to more mainstream treatment. That has been helped by the publication of a steady trickle of research papers on this subject.

Of course, a judgement must be made on a case-by-case basis but, if their doctor is happy for them to give a supplement a go, there may be little to lose and possibly much to gain.

Source: article published with permission of BLB Solicitors

New non-addictive drug may be better painkiller than morphine

Nanotechnology
(c) BLB Solicitors

Feb 15th, 2019 | article by Richard Lowes

We have considered in an earlier article how nanotechnology – science and engineering on an extremely small scale – may help to revolutionise medicine, including the way that drugs act within the body.

We have considered in an earlier article how nanotechnology – science and engineering on an extremely small scale – may help to revolutionise medicine, including the way that drugs act within the body.

The increased focus in recent years on opioid dependency among people suffering chronic pain has served to intensify the race among nanotechnologists to find new types of drugs and delivery systems which are as effective as opioids but with less risk of addiction. One particular direction which has been explored is the possibility of harnessing substances that occur naturally in the human body, thereby reducing the possibility of addiction.

Enkephalin

One such substance is a peptide called enkephalin, a naturally occurring opioid-like substance which is released by neurons in the central nervous system. It has the potential to be a very potent painkiller, but on its own it has a significant limitation – it struggles to cross the crucial blood-brain barrier to bind with its corresponding opioid-receptor system. So that’s where nanotechnology is coming to the rescue.

Promising results

Researchers in France have been successful in coating enkephalin in nanoparticles, likened to a type of biological fat. This coating makes it far easier for enkephalin to cross the blood-brain barrier to locate its corresponding receptor system.

Early results seem extremely promising and an additional benefit is that the painkilling effect seems longer lasting than morphine. The researchers say:

Although further studies are needed to more precisely determine how dosage, administration frequency, and timing of treatment with [coated enkephalin] may affect the clinical outcome, this study opens a new exciting perspective for an efficient treatment of intense pain, which evades the severe side effects associated with morphine or related synthetic opioids.

In addition, the versatility of this technology means that there is huge potential to use it as a delivery system for other types of naturally occurring substances which may have a pharmaceutical value.

The increased focus in recent years on opioid dependency among people suffering chronic pain has served to intensify the race among nanotechnologists to find new types of drugs and delivery systems which are as effective as opioids but with less risk of addiction. One particular direction which has been explored is the possibility of harnessing substances that occur naturally in the human body, thereby reducing the possibility of addiction.

Enkephalin

One such substance is a peptide called enkephalin, a naturally occurring opioid-like substance which is released by neurons in the central nervous system. It has the potential to be a very potent painkiller, but on its own it has a significant limitation – it struggles to cross the crucial blood-brain barrier to bind with its corresponding opioid-receptor system. So that’s where nanotechnology is coming to the rescue.

Promising results

Researchers in France have been successful in coating enkephalin in nanoparticles, likened to a type of biological fat. This coating makes it far easier for enkephalin to cross the blood-brain barrier to locate its corresponding receptor system.

Early results seem extremely promising and an additional benefit is that the painkilling effect seems longer lasting than morphine. The researchers say:

Although further studies are needed to more precisely determine how dosage, administration frequency, and timing of treatment with [coated enkephalin] may affect the clinical outcome, this study opens a new exciting perspective for an efficient treatment of intense pain, which evades the severe side effects associated with morphine or related synthetic opioids.

In addition, the versatility of this technology means that there is huge potential to use it as a delivery system for other types of naturally occurring substances which may have a pharmaceutical value.

Source: article published with permission of BLB Solicitors

Ambroxol: a wonder drug for neuropathic pain?

Ambroxol
(c) BLB Solicitors

Feb 15th, 2019 | article by Richard Lowes

Ambroxol is a drug that breaks up phlegm. As such it is used in medicines for the treatment of conditions which result in airway congestion such as asthma, bronchitis, coughs and colds. More recently, however, studies have shown that it may also be an effective drug for the treatment of the symptoms of neuropathic pain.

Ambroxol is a drug that breaks up phlegm. As such it is used in medicines for the treatment of conditions which result in airway congestion such as asthma, bronchitis, coughs and colds. More recently, however, studies have shown that it may also be an effective drug for the treatment of the symptoms of neuropathic pain.

CRPS

In a 2018 study, eight patients who had suffered Complex Regional Pain Syndrome (CRPS) for less than 12 months were treated with ambroxol as a topical cream in a concentration of 20%. The researchers found that “Following treatment we found a reduction of spontaneous pain (6 patients), pain on movement (6 patients), edema (seven patients), allodynia (six patients), hyperalgesia (seven patients), reduction of skin reddening (four patients), improvement of motor dysfunction (six patients) and improvement of skin temperature (four patients).

Unsurprisingly, this led them to conclude that “Topical treatment with ambroxol cream may ameliorate symptoms of CRPS.

Fibromyalgia

2017 saw the publication of two studies into the effect of ambroxol on the symptoms of Fibromyalgia.

The first study involved 25 patients taking ambroxol orally, three times a day for a month. This was a very small-scale, short-term pilot study and researchers warned additionally that the open nature of the study did not allow them to rule out the possible role of the placebo effect in the results. However, the drug was said to be “well tolerated” and “side effects were minor”. The conclusion was that “the use of ambroxol was associated to decreased fibromyalgia pain and improved fibromyalgia symptoms.

In the second study, which was entitled “Ambroxol for the treatment of fibromyalgia: science or fiction?”, the authors concluded that “fibromyalgia treatment with ambroxol should be systematically investigated, since this compound is the only treatment option used thus far that has the potential to address not just individual but all of the aforementioned aspects of pain.

That’s quite a statement! However, they were swift to stress that it’s still early days and that “at this point, the evidence base for ambroxol is currently not strong enough for clinical recommendation.

Trigeminal Neuralgia

January 2019 saw the publication of another small-scale study involving the use of ambroxol as a topical cream. This time, “clinically significant pain relief” was seen within 15 to 30 minutes in patients suffering Trigeminal Neuralgia who applied the cream following a pain flare. Pain relief was said to last between 4 and 6 hours and “in one case pain was eliminated after 1 week.

In fact, so impressed were the researchers that they concluded “In view of the positive side effect profile, topical ambroxol for patients with such a highly impaired quality of life should be investigated further as a matter of urgency.

How does ambroxol work?

It is thought that ambroxol’s analgesic properties arise from its action as a potent sodium and calcium channel blocker. It is these channels within the peripheral nervous system that carry pain signals. Other studies also note its anti-inflammatory properties.

Preliminary conclusions

Clearly, researchers in all of the small-scale studies published so far believe that ambroxol shows real promise as a treatment for the symptoms of a variety of types of neuropathic pain. However, the reality is that the current absence of large-scale clinical trials means that it is years from reaching the market. This is a huge shame because, as far as can be determined currently, unlike so many other drugs used in the treatment of neuropathic pain, ambroxol seems to be both non-addictive and to have very few side-effects. An added benefit is that, in certain situations, it can be applied topically.

Fortunately, at the very least there does seem to be a desire among the research community to push forward with larger-scale studies. Unfortunately, as with so many other promising treatments and therapies for chronic pain, it is yet another example of ‘watch this space’!

CRPS

In a 2018 study, eight patients who had suffered Complex Regional Pain Syndrome (CRPS) for less than 12 months were treated with ambroxol as a topical cream in a concentration of 20%. The researchers found that “Following treatment we found a reduction of spontaneous pain (6 patients), pain on movement (6 patients), edema (seven patients), allodynia (six patients), hyperalgesia (seven patients), reduction of skin reddening (four patients), improvement of motor dysfunction (six patients) and improvement of skin temperature (four patients).

Unsurprisingly, this led them to conclude that “Topical treatment with ambroxol cream may ameliorate symptoms of CRPS.

Fibromyalgia

2017 saw the publication of two studies into the effect of ambroxol on the symptoms of Fibromyalgia.

The first study involved 25 patients taking ambroxol orally, three times a day for a month. This was a very small-scale, short-term pilot study and researchers warned additionally that the open nature of the study did not allow them to rule out the possible role of the placebo effect in the results. However, the drug was said to be “well tolerated” and “side effects were minor”. The conclusion was that “the use of ambroxol was associated to decreased fibromyalgia pain and improved fibromyalgia symptoms.

In the second study, which was entitled “Ambroxol for the treatment of fibromyalgia: science or fiction?”, the authors concluded that “fibromyalgia treatment with ambroxol should be systematically investigated, since this compound is the only treatment option used thus far that has the potential to address not just individual but all of the aforementioned aspects of pain.

That’s quite a statement! However, they were swift to stress that it’s still early days and that “at this point, the evidence base for ambroxol is currently not strong enough for clinical recommendation.

Trigeminal Neuralgia

January 2019 saw the publication of another small-scale study involving the use of ambroxol as a topical cream. This time, “clinically significant pain relief” was seen within 15 to 30 minutes in patients suffering Trigeminal Neuralgia who applied the cream following a pain flare. Pain relief was said to last between 4 and 6 hours and “in one case pain was eliminated after 1 week.

In fact, so impressed were the researchers that they concluded “In view of the positive side effect profile, topical ambroxol for patients with such a highly impaired quality of life should be investigated further as a matter of urgency.

How does ambroxol work?

It is thought that ambroxol’s analgesic properties arise from its action as a potent sodium and calcium channel blocker. It is these channels within the peripheral nervous system that carry pain signals. Other studies also note its anti-inflammatory properties.

Preliminary conclusions

Clearly, researchers in all of the small-scale studies published so far believe that ambroxol shows real promise as a treatment for the symptoms of a variety of types of neuropathic pain. However, the reality is that the current absence of large-scale clinical trials means that it is years from reaching the market. This is a huge shame because, as far as can be determined currently, unlike so many other drugs used in the treatment of neuropathic pain, ambroxol seems to be both non-addictive and to have very few side-effects. An added benefit is that, in certain situations, it can be applied topically.

Fortunately, at the very least there does seem to be a desire among the research community to push forward with larger-scale studies. Unfortunately, as with so many other promising treatments and therapies for chronic pain, it is yet another example of ‘watch this space’!

Source: article published with permission of BLB Solicitors