Open Access CRPS Article: Pain Treatment Topics

Pain-Topics.org News/Research UPDATES

These UPDATES are a component of Pain Treatment Topics . Our mission is to serve as a noncommercial resource for healthcare professionals & their patients, providing open access to clinical news, information, research, and education for a better understanding of evidence-based pain-management practices.

Monday, September 9, 2013
Are Opioids Ineffective for Neuropathic Pain?

Neuropathic Pain
Neuropathic pain associated with various types of nerve involvement can be difficult to diagnose and treat. The use of opioid analgesic therapy is controversial due to concerns that this type of pain does not always respond well to these agents and there is potential for adverse effects. An updated systematic review examined 31 studies, involving 1,237 patients with neuropathic pain, and found intermediate-term effectiveness of opioids, but longer-term benefits for chronic conditions seem uncertain.

In this present study, Ewan D McNicol — of the Tufts Medical Center, Boston — and colleagues updated their original Cochrane systematic review first published in 2006 [McNicol et al. 2013]. As before, their assessment included randomized controlled trials (RCTs) in which opioid agonists were given to treat central or peripheral neuropathic pain of any etiology. Research trials were excluded if nonopioid drugs were combined with opioids or if opioids were administered epidurally or intrathecally.

This new review included 31 trials meeting inclusion criteria, studying 10 different opioids: 23 studies were from the original 2006 review and 8 additional studies were discovered for the update. Of the total, 17 studies — 392 participants with neuropathic pain, average 22 participants per study — provided efficacy data for acute exposure to opioids during less than 24 hours.

Most of these short-term studies (16) reported pain outcomes, and with contradictory results: 8 studies reported less pain with opioids than placebo; 2 reported that some but not all participants benefited; 5 reported no differences; and, 1 reported equivocal results. Six studies, with about 170 participants, found that mean pain scores with opioid were only about 15/100 points less than with placebo.
[....] [two large paragraphs are refusing to copy, please consult the original article by clicking on the title.]

COMMENTARY:
Trials included in the systematic review by McNicol and colleagues examined various painful neuropathies, but predominantly postherpetic neuralgia and peripheral diabetic neuropathy. Few trials included patients with back pain primarily of neuropathic origin, which may be common in some patient populations.
This could be important, since it often is difficult to diagnose back pain as being purely neuropathic in origin, without also including a nociceptive component that might be amenable to opioid therapy. Along with that, in the current review, there were insufficient numbers of participants diagnosed with each type of neuropathy to perform subanalysis of efficacy or safety, which lessens the precision and clinical usefulness of the conclusions.
McNicol et al. suggest several other points of some importance….

• The lack of efficacy found with short-term opioid administration should not be interpreted as predictive of whether administration of opioid analgesics could be helpful longer-term for neuropathic pain in individual patients.
• Despite study limitations and possible sources of bias, the NNT outcomes (as noted above) do suggest that opioids may reduce various forms of neuropathic pain. Therefore, McNicol and colleagues suggest that “opioids at low-to-moderate doses are suitable for use over periods of weeks to months in the treatment of neuropathic pain.”
• The use of a single dimension (eg, pain scales) for efficacy assessment in the available studies is problematic, since neuropathic pain is a multidimensional phenomenon that varies from one patient to the next. Also, it is important to demonstrate improvements in specific features of neuropathic pain (eg, evoked or burning pain, etc), in emotional or physical aspects of functioning, and/or in health-related quality of life that might be expected of truly effective analgesic therapy.
• The meta-analyses conducted in this review showed similar opioid responsiveness for neuropathic pain of central and peripheral etiologies, but data were insufficient to resolve any debate regarding the differential efficacy of opioids for these two types of pain.
• A dose-dependent analgesic effect was found in 2 studies examined in the review; however, the dose ranges tested were still in the low-to-intermediate range and may not necessarily reflect clinical practice in some countries. McNicol et al. state, “This, along with increasing concerns about opioid toxicity, especially at higher dose ranges (greater than the daily equivalent of 200 mg of oral morphine), does not support the use of high doses of opioids for the relief of neuropathic pain.”

It is always amazing, yet important, that so many persons with pain are willing to participate in placebo-controlled trials, knowing (due to informed consent) that there is a chance they will not be administered active-drug therapy. Despite this, only 12% of participants receiving placebo withdrew due to a lack of analgesic efficacy, which suggests a considerable placebo effect in such trials. At the same time, NcNicol et al. concede that participants willing to enter these trials may not always be typical of those in everyday clinical practice.
Furthermore, the researchers observe, “intermediate-term studies are more clinically relevant than short-term studies because they assess the benefits and risks associated with opioid treatments for weeks to months; that is, they reflect how opioids are administered for neuropathic pain in clinical practice.” They conclude that intermediate-term opioid treatment has a beneficial effect over placebo for spontaneous neuropathic pain as measured by both number of participants with at least 33% and at least 50% pain relief and in mean differences in post-intervention pain intensity.
At present, however, there are inadequate data to demonstrate improvements in many aspects of emotional or physical functioning afforded by opioids in treating neuropathic pain. And, despite the favorable intermediate-term outcomes regrading pain relief, research data are lacking to verify whether opioids may provide relief of chronic neuropathic pain during administration periods longer than 6 to 12 weeks.
REFERENCE: McNicol ED, Midbari A, Eisenberg E. Opioids for neuropathic pain. Cochrane Database of Systematic Reviews. 2013, Issue 8, Art. No. CD006146 [abstract here].

PLoS and Open Access: Research is finally getting sexy

open access logo
ripped off from PLoS ONE, Open Access, and the Futureof Scholarly Publishing

Just assuming that CRPS was more of an orphan disease this year than last, I had not noticed that my MedWorm feed results were no longer arriving. Either MedWorm has gone kaput or they're renovating, but there's been nary a word of CRPS happenings since very early in January.

So while they sort that out, I'll just do the oh-so-hard work of plugging in a few terms into the Entrez cross-database search engine at NCBI. Excuse me while I wipe the sweat from my brow.

And puh-leeze, if you're tech savvy enough to search out blogs 'n such, you're plenty capable of sorting through a couple of hundred articles and thousands of abstracts to find *exactly* that aspect of CRPS you're researching.

So here is a link, an exciting one, to PMC's (that's PubMed Central, part of the US National Library of Medicine, National Institutes of Health) current listing of 719 articles "about" CRPS that are available FREE, online.  You know how I feel about FREE!

----->> PubMed Central: free, full text journal articles -- and please note that I did a simple, one-item search.  You'll be richly rewarded the more you hone your search terms, though it does help to "go large," and then narrow down.

Just to share a bit of what you can expect as a reward, the first article that pops up is titled "Complex Interaction of Sensory and Motor Signs and Symptoms in Chronic CRPS," and its introduction is very layperson friendly:

Complex Regional Pain Syndrome (CRPS), mostly regarded as a neuropathic pain disorder, is typically evolving after a minor trauma of the limb [1]. Besides pain, CRPS displays a multifaceted clinical pattern consisting of vaso- and sudomotor changes, as well as trophic and motor disturbances, edema and somatosensory changes [2]. In consequence, many patients sustain impairments of hand function persisting even many years after the initial trauma [3]. The clinical presentation, and therefore the criteria leading to the diagnosis of CRPS, are mostly applied to patients with recently emerging, “acute” CRPS [1], [4]. Much less is known about the occurrence of the respective signs and symptoms when the initial phase of the disease subsides. Furthermore, the underlying pathophysiology of CRPS is still under debate [5]. Some authors stress the role of peripheral pathomechanisms, namely peripheral neurogenic inflammation and small fiber axonal degeneration [6], [7]. In addition, autoimmune dysfunction seems to be involved in CRPS pathomechanisms [8]. Contrariwise, a distinguished body of literature supports the involvement of the central nervous system in terms of sensory as well as motor adaptive changes[9], [10]. More generally, the level of accompanying chronic stress and depression might also account for somatosensory changes and the level of ongoing or evoked pain particularly in chronic pain patients[11], [12]. However, the degree of stress and depression in patients with chronic CRPS is not well characterized. Recently, it has been suggested that the pathophysiological mechanisms of CRPS follow a distinct time course, with a preponderance of peripheral inflammation and beginning of small fiber degeneration in the acute phase, and progression of small fiber degeneration as well as central pathomechanisms dominating the chronic phase of the disease [13]. It is still unclear to which degree the underlying pathophysiological mechanisms predict the clinical presentation of CRPS and the resulting outcome of the disease, although recent studies suggest an interdependency between the clinical presentation, the underlying pathophysiology and possible consequences in terms of resulting impairments. Namely, differences in skin temperature might facilitate the discrimination between an ongoing peripheral or central pathophysiology. [14]. So far, many clinical studies focused on the characterization of different specific aspects of the disease, for example the degree of neurological changes or the description of motor impairments [15], [16]. Furthermore, many studies mixed patients with short duration of the disease with those suffering from chronic CRPS. Up to now, a comprehensive survey linking quantitative sensory changes to CRPS symptomatology and the degree of resulting impairment is still unavailable for patients with chronic CRPS. In order to expand the knowledge of clinical characteristics of chronic CRPS and the level of concomitant stress and depression, as well as to characterize the degree of resulting hand impairment and disability, this study was performed.

Published by PLoS ONE, the entire text is there.

And now a word about PLoS ONE, and why these things get me so excited, and if you are a citizen trying to advocate for yourself or a loved one, trying to help your health care professionals out when dealing with an obscure disease, or at least, a non-sexy and underfunded one, why you should be supportive of them and excited, too!

Posted on February 14, 2013 by David Knutson  

PLOS applauds the efforts of legislation sponsors Sens. Cornyn (R-TX), and Wyden (D-OR) and Rep. Doyle (D-PA), Yoder (R-KS) and Lofgren (D-CA) with the introduction of bipartisan and bicameral legislation that will maximize the impact of federally funded research. The Fair Access to Science and Technology Research act (FASTR) act states: 

”The US has a substantial interest in maximizing the impact and utility of the research it funds by enabling a wide range of reuses of the peer-reviewed literature that reports the results of such research, including by enabling computational analysis by state-of-art technology. 

The Federal Government funds basic and applied research with the expectation that new ideas and discoveries that result from the research, if shared and effectively disseminated, will advance science and improve the lives and welfare of people in the US and around the world.  The internet makes it possible for this information to be promptly available to every scientist, physician, educator and citizens at home, in school, or in a library” 

Increasing access to research outputs delivers benefits for the economy, for medical patients, for innovators and for the general public. In Tuesday’s State of the Union Speech President Barack Obama referenced the Human Genome Project, which has generated both good science and $141 dollars returned for every dollar spent. In addition, one of President Obama’s distinguished guests was Jack Andraka, a high school sophomore, who won the 2012 Intel International Science and Engineering Fair for his creation of a new method to detect early-stage pancreatic cancer. His discovery was made possible by using the research outputs he could access freely online. 

We are seeing a proliferation of increased access, from new journals to new guidelines and legislation. In the UK, PLOS strongly supports the efforts of the UK Government and Research Councils to increase access to publicly funded research. We applaud the development and implementation of policies in Ireland, Denmark, Argentina, Australia and in the European Union. We stand firmly alongside any organization or initiative that attempts to eliminate unnecessary barriers to the immediate availability, access and use of research, and we look forward to working with them in the journey towards full Open Access. 

We invite you to join us in the PLOS mission to lead a transformation in research communication for the benefit of all. We urge you to call, write or email your congressional representative and express your support for FASTR. Click here to read the Fair Access to Science and Technology Research Act.

Bipartisan, bicameral legislation, oh, excusez-moi, I've got the shivers!  If you have CRPS or any other underfunded, under-researched, and terribly depressing disease that makes you search for help and hope online at 3 AM, then support this legislation, and work to free up information.  Take a measure of control back!

Strike a blow for Quality of Life!  QOL!  ADL!  PDQ!  ASAP!  QID!  NPO!  Download and print a copy of the legislation and use it as the basis for some incredibly painful but life-affirming bit of physical therapy.  I dunno, practice turning the pages, one by one.  Lift it over your head.  Drop it and pick it up.  Throw it at some lazy, whiny person! {::ducking::} Woo hoo, life is grand!

Well, it probably shows -- I'm feeling rotten and pretending it just ain't so.  As in, seriously rotten, should probably head for the hospital rotten.  But I'm trying, also, to stick to The Plan -- minimal interventions, just putting out the 3-alarm fires, and letting this bleeping infection in my bones and the CRPS take their course.  It's a hard habit to break, wanting to call for help for every crisis.  

This is where my well-known zen-like, calm and centered self comes into play.

Oh, shut up.  I can try!

CRPS Open Access Article: BMC Neurology

Hooray, once again, for Open Access research articles from BMC Neurology.  In this instance, it's another well done bit of research that points toward... the inflammatory process. Surprise!

I'm only reproducing here the abstract and author information, so that you can decide if you'd like to pour yourself a cup or a glass of something and peruse the longer, very technical article.  This one is definitely beyond me, but there is always information to be gleaned, learning to be done.

Do you hear it?  "Tomorrow, tomorrow..." is playing somewhere nearby.  Well, I'll just crank up some Bonnie Raitt.

I'm on a Bonnie Raitt kick.

Okay, back to business.  First, a word about BMC Neurology and its publication policies:

BMC Neurology is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of neurological disorders, as well as related molecular genetics, pathophysiology, and epidemiology. 

It is journal policy to publish work deemed by peer reviewers to be a coherent and sound addition to scientific knowledge and to put less emphasis on interest levels, provided that the research constitutes a useful contribution to the field.

They have, as I said, an open-access policy to most research, as well as a freely accessible database of case reports.  It's an enlightened approach and one much appreciated by individuals and families/friends attempting to research illnesses and who are at times desperate for information that normally must be purchased on the basis of a short abstract teaser.  Just in case it hasn't sunk in yet, or you are just coming out of shock:

Open access 

All articles published by BMC Neurology are made freely and permanently accessible online immediately upon publication, without subscription charges or registration barriers... 

Authors of articles published in BMC Neurology are the copyright holders of their articles and have granted to any third party, in advance and in perpetuity, the right to use, reproduce or disseminate the article, according to the BioMed Central copyright and license agreement.

Clearly, money must change hands at some point, and this is accomplished by a system of "article-processing charges," bless their souls.  Note, however, that:  "We routinely waive charges for authors from low-income countries."

There is still time to send a Valentine!

The CRPS / RSD article in question is:

Morphological macrovascular alterations in complex regional pain syndrome type I demonstrated by increased intima-media thickness
BMC Neurology 2013, 13:14
doi:10.1186/1471-2377-13-14
Nicola Derenthal^1†, Tim Maecken^2†, Elena Krumova^1,4, Alfried Germing³ andChristoph Maier^1*

Background
Although intima-media thickness (IMT) was increased in several inflammatory diseases, studies investigating whether the inflammatory processes lead to macrovascular alteration with increased IMT in complex regional pain syndrome (CRPS) lack.


Well. Blogger HTML dislikes the Methods and Results sections of the Abstract because they come too close, in their statistical formulations, to HTML code.  Good thing this is an OPEN ACCESS research article, eh?

Conclusions

The increased IMT of peripheral arteries in CRPS suggests ongoing inflammatory process. Until now, only endothelial dysfunction has been reported. The presented morphological macrovascular alterations might explain the treatment resistance of some CRPS patients.





The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2377/13/14

Received: 14 September 2012

Accepted: 3 February 2013

Published: 6 February 2013