Guest Post: CRPS Animal Models Explained

I’ve been terribly slack updating this blog recently, so here’s a reblog of a post I originally wrote for Burning Nights, a CRPS support forum, looking at the different animal models researchers use to try and understand the condition.

Speaking of Research

The following guest post is by Dr Rosie Morland. Dr Morland recently completed a PhD in neuroscience and pain studies at Imperial College, London, and she has a particular interest in how animal models can help increase understanding of complex pain disorders. You can read more from her on her blog. The article was originally published on the Burning Nights website which seeks to raise awareness about Complex Regional Pain Syndrome (CRPS) in the UK and Worldwide. It is republished with permission from the original author and Burning Nights website. CRPS, formerly called Reflex Sympathetic Dystrophy (RSD) is a chronic pain condition which usually affects the limbs and can result in prolonged pain. More information on CRPS can be found in this leaflet.

Developing Animal Models of CRPS/RSD Explained

In the last 20 years, research into Complex Regional Pain Syndrome (CRPS) has seen huge advances, taking it from…

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Creating arrows and arrowheads in Illustrator CS6

Ah! So that’s how you do double headed arrows! Brilliant!

Photography & Illustration

There are several ways to create an arrow using Illustrator CS6. Here are five different methods that will give you a wide variety of arrows to choose from:

  • Using the Stroke Panel
  • Using Symbols
  • Using Glyphs
  • Using Brushes
  • Using Shapes

Using the Stroke Panel

In Illustrator CS6, turning any line into an arrow with arrowheads and tails is easy.

  1. Create any line (straight or curved) with two end points.
  2. With the line selected, open the Stroke panel by choosing Window > Stroke.
  3. Find the section titled “Arrowheads” and select your arrowhead and tail sections!

Below are some examples of arrows created using the Stroke panel:

Using Symbols

  1. To use the preset symbols in Illustrator CS6, open the Symbols panel by choosing Window > Symbols.
  2. In the Symbols panel, open the fly-out menu, choose “Open Symbols Library” and open the Arrows Library.
  3. From there, just drag and drop your arrows onto your artboard.

Here are some examples…

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F1000 Research, an open science journal

Very interested in this – currently preparing a paper and trying to decide between PlosOne (which is more established) and F1000 (who have approached us about showcasing our proposed publication) , and leaning towards F1000, despite the lack of impact factor (really, do they still matter? Are individual citation metrics not more useful?).

Will keep you guys posted!

Ideas for Sustainability

By Joern Fischer

Some of you may know of the Faculty of 1000. It’s a bunch of supposed “experts” who recommend papers that might be interesting to others in the field.

The Faculty of 1000 has recently launched its own research journal for the life sciences (i.e. including things like conservation biology but not including truly broad conceptions such as sustainability science) — it’s called F1000 Research. This journal is pretty different to most (all?) others out there at the moment.

When you submit your paper, it immediately goes online. All data that was part of the work (when reasonable/ethical/legal) needs to be provided, too. Next, after it’s already online people can review the papers and say they are basically sound or not sound. If something does not get any “basically sound” ratings, it gets taken off again. If it gets “basically sound” assessments, it is then possible to…

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My favourite Mendeley CSL

So, here I am, tantalizingly close to finishing my PhD thesis. The last few days I have been dealing with the Hell that MS Word becomes when you ask it to deal with formatting a document as complex as a thesis, full of citations, table and figure references, and a bunch of formatting weirdness.

I use Mendeley to manage my references, and I’ve always found it easy to use. However, when making sure my references were formatted exactly as I wanted, I had to dip my toe into CSL and make some tweaks.

So in-case anyone else out there might have use for it, here is my customised citation style:

Example of inline citation:

(Carlsson, 1983; Price et al., 1983)

Example of Bibliography:

Whishaw, I.Q., Gorny, B., Foroud, A. & Kleim, J.A. 2003. Long-Evans and Sprague-Dawley rats have similar skilled reaching success and limb representations in motor cortex but different movements: some cautionary insights into the selection of rat strains for neurobiological motor research. Behavioural brain research, 145, 221–232 Available at: [Accessed August 2, 2012].

WHO. 2013. Model Lists of Essential Medicines. World Health Organisation Publications Available at: [Accessed September 7, 2014].

Additional features include:

*Disambiguation override – Keeps initials out of inline citations (Mendley does this to distinguish multiples uses of the same citation)

*Alternate Date Options – using the ‘short name’ field, you can add your own non-date descriptor, such as “In Press/Manuscript in Preparation”

How to use multilevel numbered headings in Word 2007

For anyone who has ever wanted to throw their computer out the window when trying to deal with numbered headings in a huge document (i.e. my thesis!)… salvation is here!

MS Word Know How

Creating and fixing multi-level numbered headings in Word might seem to be a bit tricky for the first time users. Nevertheless, if you know the correct procedure, this would cease to be a problem. The following procedure may help you in this regard:

The Procedure

Firstly, we will define the multilevel numbering for the heading levels using Multilevel List feature.

1.     Open the Word document in which you want to apply numbered headings.

2.     From the Word Ribbon menu, under the tab Home and within the group Paragraph, click the Multilevel List icon multi list button .  A drop-down menu appears.

(Click the image to view in full screen)

define new multi level list

2.     From the drop-down menu, select the option Define New Multilevel List (at the bottom of the menu). The “Define New Multilevel List” dialog box pops up.

3.     Click the More button  (Picture1)  available at…

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Botox and Complex Regional Pain Disorder

One of the many things I’m involved with online is running the London Pain Consortium twitter account, and recently someone got in touch asking about botox treatment for complex regional pain syndrome (CRPS), so I decided to write a wee post summarising what is published on the subject. Please note: I am not a doctor, or a CRPS specialist! Just a bog standard pain researcher, with experience in systematic reviews…

I found 4 publications, 2 case study format, and the other 2 involving between 14 and 37 patients. 3 of these reported that botulinum A toxin (Botox) improved symptoms when injected into trigger points and other areas affected by CRPS… sounds promising, but it’s important to also look at the quality of the study before deciding to trust what it is claiming. I have an inherent distrust in case studies – for one thing, they rarely feature qualitative outcomes measures, relying more on subjective descriptions of patient condition, and for another, they are a good example of publication bias, i.e. people prefer to share the positive rather than negative. It’d be very unusual to read a published case study describing a failed treatment – the fact is, pain is such a complex condition that many treatments will only work in very narrowly defined populations, so without good information on who was treated (age, sex, weight, medical history), how they were treated (dose, injection spot, frequency), and how any changes were assessed (pain & quality of life questionnaires, sensory testing, VAS scales), it’s difficult to say how relevant or accurate their statements are.

Looking at the 4 publications again, taking into account quality of evidence presented by the study, as well as whether they said it worked or not, shows a different picture. As I mentioned, 2 were case studies:

  • The first, published in 2009, described 4 teenage patients in good detail, but failed to mention the dose, or use objective measures in reporting changes after the treatment 
  • The second, published in 2010, described 2 adult patients, and used VAS scales to objectively measure the effect of the treatment 

The third paper, is from the authors of the second case study above, and was the only study to involve a control group, or use multiple methods of assessing pain. They looked at 14 patients, with 5 different tests, but had to call the study short due to poor tolerance of the treatment. (I imagine they planned the pilot study on the basis of the case study reported above.)

The final paper, published in 2011, was completely upfront in stating its limitations – it was done retrospectively from patient records, and had no control group, meaning it’s impossible to exclude the possibility that the reported positive results are due to the placebo effect (a well known issue in clinical trials for pain conditions), or say how it compares to another, more established drug. 

In summary, my evaluation of the literature above suggests caution – although many seem positive, the quality of the studies is low, but until someone does a high quality study, it won’t be used as a standard treatment. One of the problems in the pain field in general, and with CRPS in particular, is that clear diagnosis is often difficult, and results in patient populations which may have little in common.

I’m going to look at the evidence from the pre-clinical studies next, and do a follow-up blog to see whether that has anything to add to this discussion.

As always, questions & comments welcome 🙂

Articles Cited:

  1. Syndrome of fixed dystonia in adolescents-short term outcome in 4 cases. Majumdar et al., 2009
  2. Botulinum toxin A (Botox) for treatment of proximal myofascial pain in complex regional pain syndrome: two cases. Safarpour & Jabbari 2010
  3. Botulinum toxin A for treatment of allodynia of complex regional pain syndrome: a pilot study. Safarpour et al., 2010
  4. Intramuscular botulinum toxin in complex regional pain syndrome: case series and literature review. Kharkar et al., 2011



The Science of Shotlogging

This is what happens when you let a scientist shot-log a film…

Fighting Badgers

When I first became involved with Fighting Badgers, one of the main things I did was spreadsheets. It’s a large part of my job as a research scientist, so it seemed a natural to do as the information started piling up. Contact details, scheduling information, script breakdowns… it was all there, colour coded, formatted, and gorgeous – I can’t say how glad we were for them when it did come time to start scheduling for The Ipanema File – not having the resources to use commercial scheduling software, having it all accessible by pivot table made it a lot less terrifying!

During the shoot, I was happy to take on the job of shotlogging – I knew from previous experience during the editing of Jagoda how vital accurate logs were, and as our editor was not present during the pre-production or shoot, I felt it was only fair to make…

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Object of the month: Shrunken Heads (real and fake)

Wellcome Collection Blog

As part of our development project, the tsantsa (or, shrunken head) normally on display in Medicine Man is in storage. Our replica tsantsa, however, which forms part of our cross-gallery handling collection, can still be seen. This month Charlie Morgan delves into the history and controversy of this erstwhile cultural practice.

Shrunken head, Shuar Shrunken head, Shuar

At some point in the mid-16th century, Spanish Conquistadors entered the Amazon rainforest and came into contact with the Shuar people. In the epic colonisation of Latin America, one more indigenous group would not have made much of an impact if it had it not been for two factors: gold and tsantsas. To gain the former, the Spanish Empire tore up its initial peace agreements and subjugated the Shuar in a brutal mining system. In 1599, The Shuar – amongst other Jivaroan tribes – revolted against the Spanish, sacked their towns and –…

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Will distinguishing between exploratory and confirmatory research aid translation??

This paper makes me ranty. It’s open access – take a look, and be prepared to read it more than once to get the gist of their arguments.

Published in May 2014 in PLOS Biology (who incidentally also published the ARRIVE guidelines, which, although never mentioned by name are the clear target), it focuses on the concept that there are fundamentally two types of pre-clinical research: Exploratory and Confirmatory.

Exploratory research is described as being flexible, which sounds great until you realise what the authors mean by flexible is involving minimal pre-planning, no requirement for statement of experimental parameters which can influence outcome, and an emphasis on small samples sizes, and multi-technique or conceptual confirmation of results. These techniques, incidentally, do not need to be validated or established in any way. They argue that the use of multiple techniques negates the effect of small samples sizes, without acknowledging the fact that if the initial study is underpowered and biased, then all those that follow will be similarly afflicted. This is not the definition of robust research. Oh, and they also suggest that ‘non-informative’ data can be excluded on a whim, because, obviously you as an author know better than the readers, not to mention the fact that so-called ‘outliers’ are often worth a bit of investigation – ask why are they showing such extreme values, rather than discarding because the data is tighter without their presence.

Confirmatory studies are those which are based on robust exploratory studies, which from the above description seems somewhat contradictory. How can a study be described as robust if it is underpowered and uses unvalidated techniques? The way confirmatory research is described in this article makes it sound unimaginative and a crude approximation of how most pharmaceutical pre-clinical research is conducted.

It seems to me that instead of reducing the use of animals in research, encouraging studies with group sizes plucked out of the air will just mean more waste in attempts to replicate false positives. Seriously, why not spend a little time before starting a study working out the group sizes you will need to use inferential statistics (i.e those involving a p-value for significance)… OR simply avoid the issue and use descriptive statistics only. Makes sense, no?

There are some interesting ideas in the paper (e.g. use of multiple techniques) , but it is fundamentally flawed by its emphasis on removing so-called ‘fastidious’ methodology – be robust and respectful in your studies, or they will be worthless.

So will distinguishing between exploratory and confirmatory research aid translation? Maybe, but not the way these guys see it – true exploratory research is not that widespread (e.g. ‘trawling’ studies such as GWAS, which generate potential leads); the majority of studies are ‘confirmatory’ in some form, so really the point at which exploratory research becomes confirmatory needs to be better defined… or preferably, described differently, acknowledging the diversity of contribution to clinical understanding, not just from a drug discovery standpoint.

Official responses to this publication are in the process of being prepared, so I won’t say much more except watch this space…

I am discussing the article entitled: Distinguishing between Exploratory and Confirmatory Preclinical Research Will Improve Translation, by Kimmerman, Mogil, and Dirnagl, published by PLOS Biology in May 2014. DOI: 10.1371/journal.pbio.1001863

Adventures with Lidocaine and Amitriptyline

A few months ago, I wrote of my experiences with chronic pain and I mentioned I had started a regime of amtriptyline. Well, 6months and a referral to a pain clinic later and I feel I can report on how this is going and give a little bit of insight into how this drug, better known as an antidepressant, can help with chronic pain.

Amitryptyline was first introduced in the early 60s as a treatment for depression, and is now used to treat a range of disorders including insomnia, tinnitus, ADHD, migraine and… chronic pain. So how is it able to treat such a wide range of conditions? What does it do?

It is categorized as a tricyclic antidepressant and acts primarily as a serotonin-noradrenaline reuptake inhibitor, leading to an increase in the levels of these neurotransmitters. It also has effects on a whole range of receptors and ion channels including some which have been strongly implicated in pain such as TrKA, sodium/potassium channels, and nicotinic receptors, where is it thought to suppress activity in c-fibres, nerve fibres known to be involved in transmission of pain.

Of course, the doses used vary widely between conditions – from ~100mg in depression, to the 20mg dose I take for my pain. This low dose for pain means the side effects, which can be quite an issue in depression, are less severe. I’ve spoken to a few people who’ve tried it for pain before with mixed results – the most common issue has been drowsiness, which I agree with. I take it at night, initially before I went to bed, but have recently switched to a little earlier as I think it was making mornings even more difficult… given I already need 3-4 alarms to get my ass in gear normally! However, on the pain front, its effect is pretty minor for me. The drowsiness at night is actually the main benefit, as it smooths over the stabbing pains which made it difficult to get comfortable before… I’m struggling to notice any real effect during the day on the pain levels, but it has made a noticeable difference to my quality of life, which is the main thing really. If I’ve only learnt one thing in the past 5 years in pain research, it’s that complete removal of pain is a rarely achievable goal, and most patients (myself included) massively appreciate anything that makes the experience of chronic pain easier, be it problems sleeping, difficulty concentrating, or any of the myriad other ways pain can interfere with your day to day life

…so then I finally got myself an appointment at a pain clinic, saw a doctor who actually understood what I was feeling (woo!) and immediately prescribed me lidocaine patches… and it’s no exaggeration to say these wee guys are my favourite thing at the moment! Lidocaine is a local anaesthetic, and is often found in creams to help with sunburn and itching (not to mention its other, murkier, use as a cutting agent with cocaine due to its strong numbing effects). I currently have 5% patches, which I stick on my stomach every day to help with the post-operative abdominal pain, and they are brilliant! Completely removes the pain associated with light touch that has been adding a layer of frustration to my daily life for the last year or so (ID badge? Bouncing against you while walking? Shouldn’t be painful, no?), and it seems to also act on the shooting pains (which may, or may not be neuropathic). Unfortunately, I can only keep them on for 12hrs a day, and within 10minutes of removing them, the pain tends to return, but I’ve only been using them for 3weeks so you never know.

Lidocaine patches are actually only licensed for postherpetic neuralgia associated with shingles, but have increasingly been used ‘off-label’ for conditions such as endometriosis and other pelvic pain conditions such as those associated with adhesions, as I have. Worth speaking to your GP about, although mine was very reluctant (“too expensive“) and it was only once I saw a pain specialist that I was ‘allowed’ them, so there we go.

I was also given a TENS machine, which I’ve played with a bit, but I think I need to go back and get some advice on positioning of electrodes and the best settings to use as they’re not actually advised for use in the abdominal area for reasons I can well understand – some of my experiments with positioning have caused weird sensations all down my leg or in other areas which don’t quite feel right. If anyone reading this has experience with using TENS abdominally, I would really welcome some tips on settings and positioning!!

Anyway, that’s all from me for now – as always, feel free to ask any questions or leave any comments as I’d love to hear from you!