CRPS Case Study: Recurrence After Use of Capsaicin patch

This is not me... but I've closely resembled this highly inflamed "red stage" in both hands and feet. The skin in CRPS' red phase can radiate heat that can be felt from a foot away.  This is close to how my extremities react to applications of lotions, medicated creams and patches.

Although this article has the limitations inherent to any case report, I am grateful to see it.  Just by coincidence, I've been inundated with suggestions from well-intentioned curious medical types about what lotions or patches I should apply to my legs and hands.  My response, that applying anything beyond the special antibiotic soap (a 2% solution of Hibiclens), any lotion, oil, or capsaicin cream/patches, lidocaine patches, cause an extreme, immediate, and long-lasting inflammatory response.  My entire lower leg or forearm immediately swells, turns boiled-lobster red, with what almost seems a boiled-lobster temp, and -- just for giggles -- breaks out in... welts.  Welts?  (I don't really know what to call them... maybe they're bubonic plague bullae or maybe they're more akin to a mess o'flea bites, whatever is ugliest or über gross.  Fluid-filled and not itchy, oh no, that would be too pleasant -- because they burn.)

Anyway, it's hard to explain why I cannot lather my extremely dry skin with soothing emollients... so as I said -- I'm grateful to see this case study!

Yes, damn it, I did recently praise myself to High Heaven for my circumspect descriptions of CRPS' impact on my body.  Be divine, and forgive the occasional slip-up?

In other news, I am multi-tasking my efforts at distraction for pain relief, and that's meant excessive television viewing these past few days.  Did you know there is an Amish Mafia?  Live and learn.  The episode blasting in the background right now features Big Bad Lebanon Levi and the "fights" -- they have MMA matches.  Good Wikipedia warns me, however, that the whole show may be nothing but lies, legends, and nonsense.  Whew.  Back to the norm for "reality" television.

Ahem, without further ado, here's the abstract of the case study in question:


Der Schmerz. 2012 Dec 9.

Pronounced symptom deterioration in complex regional pain syndrome type II after isolated application of a highly concentrated capsaicin patch : A case report.

[Article in German]

Girtler R, Kloimstein H, Gustorff B.

Abteilung für Anästhesie, Intensiv- und Schmerzmedizin, Wilhelminenspital der Stadt Wien, Montleartstr. 37, 1160, Wien, Österreich, richard.girtler@wienkav.at.

Abstract
Topical 8 % capsaicin is an established therapeutic option for the treatment of peripheral neuropathic pain. In accordance with the internationally accepted definition, complex regional pain syndrome (CRPS) type II is a form of neuropathic pain so that capsaicin plasters represent a treatment option. However, for the treatment of CRPS it is recommended that painful stimuli should be avoided but capsaicin induces a strong nociceptive stimulation and so its use is at present controversial.We report on the course of such an application in a patient who developed CRPS type II with intractable neuropathic pain after hallux surgery. As a result of a single treatment with capsaicin a pronounced recurrence developed with central nervous symptoms.


Further Resources:
First two pages of text (the second has several photos)

References:

1. Anand P, Bley K (2011) Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. Br J Anaesth 107:490–502 CrossRef
2. Cheshire WP, Snyder CR (1990) Treatment of reflex sympathetic dystrophy with topical capsaicin. Case report. Pain 42:307–311 CrossRef
3. Harden RN (2005) Pharmacotherapy of complex regional pain syndrome. Am J Phys Med Rehabil 84:17–28
4. Harden RN (2010) Validation of proposed diagnostic criteria (the „Budapest criteria“) for complex regional pain syndrome. Pain 150:268–274CrossRef
5. Lanz S, Maihöfner C (2009) Symptome und pathophysiologische Mechanismen neuropathischer Schmerzsyndrome. Nervenarzt 80:430–444CrossRef
6. Mackey S, Feinberg S (2007) Pharmacologic therapies for complex regional pain syndrome. Curr Pain Headache Rep 11:38–43 CrossRef
7. Perez RS, Zollinger PE, Dijkstra PU et al (2010) Evidence based guidelines for complex regional pain syndrome type 1. BMC Neurol 10:20CrossRef
8. Ribbers GM, Stam HJ (2001) Complex regional pain syndrome type I treated with topical capsaicin: a case report. Arch Phys Med Rehabil 82:851–852 CrossRef
9. Ribbers GM, Geurts AC, Stam HJ et al (2003) Pharmacologic treatment of complex regional pain syndrome I: a conceptual framework. Arch Phys Med Rehabil 84:141–146 CrossRef
10. Robbins WR, Staats PS, Levine J et al (1998) Treatment of intractable pain with topical large-dose capsaicin: preliminary report. Anesth Analg 86:597–583
11. Eisenhart-Rothe R von, Rittmeister M (2004) Medikamentöse Therapie des komplexen regionalen Schmerzsyndroms Typ I. Orthopade 33:796–803
12. AWMF-Leitlinien-Register Nr. 030/116 (2008) Diagnostik und Therapie komplexer regionaler Schmerzsyndrome (CRPS). Leitlinien für Diagnostik und Therapie in der Neurologie, 4. überarbeitete Aufl. Georg Thieme, Stuttgart

Description of Journal Der Schmerz

ISSN: 0932-433X (Print) 1432-2129 (Online)
Description
Zielsetzung der Zeitschrift Der Schmerz ist ein international angesehenes Publikationsorgan und wendet sich an Ärzte aller Fachgebiete sowie an Allgemeinmediziner und Psychologen, die mit der Behandlung von Schmerzpatienten oder in der Schmerzforschung beschäftigt sind. Das Ziel der Zeitschrift ist es, die Versorgung von Schmerzpatienten langfristig zu verbessern. Praxisorientierte Übersichtsarbeiten greifen ausgewählte Themen auf und bieten dem Leser eine Zusammenstellung aktueller Erkenntnisse aus allen Bereichen der Schmerzforschung und Symptomkontrolle bei Schmerz. Neben der Vermittlung von relevantem Hintergrundwissen liegt der Schwerpunkt dabei auf der Bewertung wissenschaftlicher Ergebnisse unter Berücksichtigung praktischer Erfahrung. Frei eingereichte Originalien ermöglichen die Präsentation wichtiger klinischer Studien und dienen dem wissenschaftlichen Austausch. Kasuistiken zeigen interessante Fallbeispiele und ungewöhnliche Krankheits- bzw. Behandlungsverläufe. Beiträge der Rubrik „CME: Weiterbildung – Zertifizierte Fortbildung“ bieten gesicherte Ergebnisse wissenschaftlicher Forschung und machen ärztliche Erfahrung für die tägliche Praxis nutzbar. Nach Lektüre der Beiträge kann der Leser sein erworbenes Wissen überprüfen und online CME-Punkte erhalten. Die Rubrik orientiert sich an der Weiterbildungsordnung des Fachgebiets.
Aims & Scope Der Schmerz is an internationally recognized journal and addresses all scientists, practitioners and psychologists, dealing with the treatment of pain patients or working in pain research. The aim of the journal is to enhance the treatment of pain patients in the long run. Review articles provide an overview on selected topics and offer the reader a summary of current findings from all fields of pain research, pain management and pain symptom management. Freely submitted original papers allow the presentation of important clinical studies and serve the scientific exchange. Case reports feature interesting cases and aim at optimizing diagnostic and therapeutic strategies. Review articles under the rubric “Continuing Medical Education” present verified results of scientific research and their integration into daily practice. Review All articles of Der Schmerz are peer reviewed. Declaration of Helsinki All manuscripts submitted for publication presenting results from studies on probands or patients must comply with the Declaration of Helsinki. Indexed in Science Citation Index Expanded, Medline, Neuroscience Citation Index, Research Alert, EMBASE and Scopus.

Intrathecal Baclofen in CRPS

Anesthesia & Analgesia 2013 Jan; 116(1):211-5.

Efficacy of intrathecal baclofen on different pain qualities in complex regional pain syndrome.

van der Plas AA, van Rijn MA, Marinus J, Putter H, van Hilten JJ.

Department of Neurology, Leiden University Medical Center, PO Box 9600, 2300 RC
Leiden, the Netherlands.  A.A.van_der_Plas@lumc.n.

BACKGROUND: Complex regional pain syndrome (CRPS) is characterized by severe
debilitating chronic pain. Patients with CRPS may experience various pain
sensations, which likely embody different pathophysiologic mechanisms. In this
study, we evaluated the differential effects of central γ-aminobutyric acid (B)
receptor stimulation on the different pain qualities in CRPS patients with
dystonia.

METHODS: The 10 pain qualities of the neuropathic pain scale, dystonia severity,
and changes in use of antinociceptive drugs were evaluated every 3 months for a
period of 1 year in 42 CRPS patients with dystonia receiving titrated doses of
intrathecal baclofen (ITB) treatment in an open design.

RESULTS: Using a linear mixed model analysis and controlling for global dystonia
severity and the use of supplemental analgesics, we found a significant
improvement in global intense pain, sharp pain, dull pain, and deep pain during
the first 6 months. After this period, the scores leveled off despite further
improvement of dystonia and continued ITB dose escalation.

CONCLUSIONS: γ-Aminobutyric acid (B) receptor stimulation by ITB exerts
differential antinociceptive effects on specific pain qualities in CRPS patients
with dystonia.

PMID: 23223108  [PubMed - in process]


RELATED CITATIONS (101 results)

Have you seen Scott Reuben?

Another bit of housekeeping, this related to a promise to keep half-an-eye on ex-con physician Scott Reuben.  To read my previous posts on "doctor" Reuben, click HERE.  While we wait for him to make [up] the news again, here's the obvious question on many peoples' minds:

Big Pharma's Ghostwriters
Why Are These Fraudulent Papers Unretracted?
by MARTHA ROSENBERG

According to Science Times, the Tuesday science section in the New York Times, scientific retractions are on the rise because of a “dysfunctional scientific climate” that has created a “winner-take-all game with perverse incentives that lead scientists to cut corners and, in some cases, commit acts of misconduct.”

But elsewhere, audacious, falsified research stands unretracted–including the work of authors who actually went to prison for fraud!

Richard Borison, MD, former psychiatry chief at the Augusta Veterans Affairs medical center and Medical College of Georgia, was sentenced to 15 years in prison for a $10 million clinical trial fraud[2] but his 1996 US Seroquel® Study Group research is unretracted.[3] In fact, it is cited in 173 works and medical textbooks, misleading future medical professionals.[4]


Scott Reuben, MD, the “Bernie Madoff” of medicine who published research on clinical trials that never existed, was sentenced to six months in prison in 2010.[5] But his "research" on popular pain killers like Celebrex and Lyrica is unretracted.[6] If going to prison for research fraud is not enough reason for retraction, what is? [Please read the rest of the article HERE.]



[1] http://www.nytimes.com/2012/04/17/science/rise-in-scientific-journal-retractions-prompts-calls-for-reform.html?_r=1&pagewanted=all

[2]  Steve Stecklow and Laura Johannes, “Test Case: Drug Makers Relied on Two Researchers Who Now Await Trial,” Wall Street Journal, August 8, 1997

[3] Richard Borison et al., “ICI 204,636, an Atypical Antipsychotic: Efficacy and Safety in a Multicenter, Placebo-Controlled Trial in Patients with Schizophrenia,” Journal of Clinical Psychopharmacology 16, no. 2 (April 1996): 158–69

[4] Alan F. Schatzberg and Charles B. Nemeroff, Textbook of Psychopharmacology (New York: American Psychiatric Publishing, 2009) p. 609

[5] http://www.scientificamerican.com/article.cfm?id=a-medical-madoff-anesthestesiologist-faked-data

[6] Scott Reuben et al., “The Analgesic Efficacy of Celecoxib, Pregabalin, and Their Combination for Spinal Fusion Surgery,” Anesthesia & Analgesia 103, no. 5 (November 2006): 1271–77.

Have You Seen Lindsey Baum?

All previous blog posts about missing child Lindsey Baum

There is no news about missing child Lindsey Baum but I've been remiss at keeping her name and face fresh here... The following is taken from the initial page of the Official Website for Missing Child Lindsey Baum.

At *this* moment, it has been 1290 Days, 16 Hours, 36 Minutes, and 31 Seconds since her abduction.


Lindsey Jo Baum 

Missing Since: 06/26/09
Missing From: McCleary, WA
Classification: Endangered Missing
Age at Disappearance: 10
Date Of Birth: 07/07/98
Height: 4’10
Weight: 90 lbs
Eyes: Brown
Hair: Brown/Dark Blonde
Colored fillings in her teeth
Clothing: long sleeve hooded shirt (not sweatshirt) light bluish/gray, jeans with knees cut out, black slip on american eagle shoes with white rubber soles, no socks. bathing suit under clothes red/white/blue in color for both pieces but mismatched bottoms a floral print, top stripes and polka dots.

Details of Disappearance:

Lindsey disappeared on June 26,2009 while walking home [from a friend's home] in McCleary, WA at about 9:30 in the evening. This was one of the longest days of the year and didn’t get dark until around 10:30 that night. It was still daylight out as she left for the short 5-10 minute walk home.

She never made it home that night.

Who to Contact with Information:
Grays Harbor County Information Hot-line (Tip line) (866) 915-8299, Email: soadmin@co.grays-harbor.wa.us or you may submit a tip via the contact us link on Lindsey’s Official website and the information will be passed on to the Law Enforcement officials working Lindsey’s case.
[OR DIAL 911]

CRPS: Feet Update

It's many hours later. I am enjoying the season premier of Downton Abbey and was thrilled to discover that the DVR has also, apparently of its own volition, recorded a good many of the old Upstairs, Downstairs, and I guess these tidbits of confessional viewing habits tell you quite a bit!

Fred cannot abide looking at my hands.

He offers, freely, and with good intentions, to do anything for me -- I've but to ask. I've asked many times for help with my feet, until now the asking has degenerated into jokes (jokes unreceived, unnoticed but jokes, still -- usually something about a "spa").

They need tender, loving care, as the saying goes. Then reality sets in... you cannot touch the buggers without eliciting a scream or a melodramatic moan that attempts octaves. Even if I manage a good measure of pain control, and keep a hold on my emotions, as well, I cannot bring myself to ask for tender, loving care. It requires definition for Fred, detail, a play-by-play description of what and how and, even, why. It bleeds every bit of the tender, loving care from the process before it begins, so it never, ever... begins.

I want human touch, warmth, sweet-smelling waters, I want to see love of my feet shine in his eyes. Lotions of any sort just incite inflammation, burning, swelling, and the reddest red you've never seen. My feet will spend at least 12 hours emanating unbelievable amounts of heat just from the application of a simple cream. You can feel a force field, a threatening volcano, holding your hand a foot away. Do I exaggerate? No. The words get weird, the words get strange, the attempt to make someone understand ruins language, and makes me an object of ridicule. I've learned to shut up, to make my descriptions brief and ordinary. The weirdness of CRPS interests no one, not even the scientific types who ought to be interested in accuracy. I could tell a researcher that my pain level was an 8 or 9 out of 10, which would caused a brief raised eyebrow of disbelief or I could calmly explain:

What's the pain like? Like a thousand tiny paper cuts, never cleansed, reopening with every step. Like scrubbing the kitchen floor and ammonia spills onto an open wound. Like Fourth of July sparklers spitting through my foot and leg. Like a Kansas City hail storm raging through my foot. Like Dante's words in The Inferno when he wrote [my pain is] "….ever burning, but never consumed."

Not my words, obviously, being so circumspect and free of obscenity. It's a description I ran into while grazing around the RSDSA website, choosing to expose my cynical, nasty self to a section called "Stories of Hope." The quote is from one Kathleen Campbell, M. Div, in a fine piece called "Transformation and Hope—The Means to Recovery." It leaped off the page, buried as it was in cool, pastoral prose, and that levelheadedness one assigns to people who counsel others with all expectation of success. I routinely beg CRPSers not to talk about feeling doused with gasoline and set on fire... but not entirely for the reasons you probably assume! Mostly, it's because few of us have had the experience, though we all share dreams of self-immolation, flirting with a notion of martyrdom just to elevate this trashpile of an experience to something with a more ennobling history.

Thích Quảng Đức in the full photo of his self-immolation,
 in protest of South Vietnam's
Roman Catholic government's persecution of Buddhists, during which
he remained perfectly still.
It was a Pulitzer Prize-winning photograph by Malcolm Browne.

Over the ten years I've "had" CRPS, I've managed to hem in and refine my verbal descriptions of CRPS pain, except, as you, Dear Reader. can attest, for the pages of this blog.

"It's Hell," I say.

I don't suppose any of us really share a clear notion of what Hell is like, but I've noticed that following its mention, the eyes slightly lose focus, and there's often a flicker of fear.

And I've yet to be made fun of for saying it.

But I'd rather the medical types listen to the fine details:  though the right leg is more edematous, and the pain deep and throbbing, extending from inside the right prosthetic hip to the tips of the twinkling toes, and is covered with strange outbreaks, sometimes blisters -- it is the left leg and foot that cause me to issue regular invitations to Do-It-Yourself Amputations and Bar-B-Ques.  The left leg's pain is intolerable and usually the instrument of those God-damned spasms.

See?  It's best not to allow even the specialists to query one's pain.  The truth?  It's not that they cannot "handle the truth..." It's just that no one can sit quietly in the company of, in the contemplation of a personal Hell.

Still there?

If you are, don't blush or get over-emotional, but I love you.  (Fat chance that I'll admit it in the morning...)

If It's Sunday, It's Bad Videos!

I'm going out on a limb and declaring someone's search for "baclofen porn" to be the weirdest search of this blog to date.  Baclofen is a drug for spasticity.  Baclofen porn?  I cannot even imagine what that means, but I'd love to know.  So... whomever you are, s'plain yourself!

Late last night, I decided to reintroduce myself to some of the minor technology that has piled up in our well-appointed apartments here in the West Wing of Marlinspike Hall.  Won't bore you with long stories about Best Buy, UPS, Amazon... but will divulge that they did not come off as brilliant marketers over the holidays.

I had trouble sleeping so I loaded and tweaked and played with a new mp3 player that will hold more than the 6 songs my last one managed.  I did the tweaking and playing part of that in the soft swinging hammock of the velvety dark -- and was repeatedly attacked by one Buddy, the outrageously large kitten, our Maine Coon.  He's undergoing yet another growth spurt and that means, too, a certain recidivism in his behaviors, mostly chewing -- wires, anything plastic, doors, canes, wheelchair wheels.  I got him settled down, eventually, by doing what he cannot resist -- toy with his elastic ears.  Pulling them, scratching them, praising their magnificence.  I set the player to a 60-minute sleep mode, blew all the tension out of my body via my mouth, and let my mind go with the music.

The little faker.  Five minutes into my relaxation, KABOOM.  Imagine Buddy landing on your chest, claws clawing, vocalizing like a feline maniac, going after those noisy little wires, yanking the earbuds from your aural cavity with fierce violence.

He's fascinated with music.  Or noise.  Fred bought an old spinet piano several weeks ago, and Buddy lurks as Fred pecks at the newly tuned keys, looking over his shoulder, trying to find a way inside (what is a piano, after all, but a big box?).  He walks on the keys, jumping straight in the air sometimes at the sound he himself produced.

Yeah, so another piece of electronics that mocks me is the video camera,  I loved my little Flip thingy, but I also dropped it into a sink full of hot soapy water.  The new one, refurbished, is a mainstream model, meaning:  it's not for me!  I can't get my hands to find one ergonomic boon in the design of the thing.

So, of course, we decide we're gonna make a movie of Buddy and the Piano.  I dug through piles of buzzing, whirring electronic gadgets, found the camcorder, and did a test shot of the Maine Coon flexing his paws and claws in preparation for a Beethoven piece he's been practicing.




Then, of course, as we proceeded in solemn cortège to the funky spinet piano (for which Fred has yet to purchase a bench), and Fred began a rousing version of Oh My Darling Clementine while the cat lolled on the cat tree just behind Fred's right shoulder.  Buddy mostly stared (glumly, very glumly) at me and the stupid camera.

The stupid camera's battery died.

Okay, fine.  So this morning, after the Night of MP3 Battles, I figured I would get the now properly charged camera out for some practice.  It requires too much of my hands but practice can occasionally improve performance, I hear.

But I only produced nonsense.  So, of course, I am posting it, with these caveats:
1.  I know my house is a mess, so hush;
2.  No, I do not abuse Miss Marmy Fluffybutt, I don't care what she tells the SPCA;
3.  I know my filming skills suck, thankyouverymuch (see aphorism about "practice" above)
4.  Fred was worshiping with the Militant Lesbian Existential Feminists;
5.  Yes, I know my feet and hands don't "look right." I have CRPS, you ninny;
6.  I'm really sorry for posting junk... but I am bored and the only other things to do right now are dishes, laundry, and vacuuming;
7.  Ignore the raspy voiced narrator, she is an idiot.

Oh, and I promise not to encourage Buddy in his interest in the microwave.






okay, so this video is even worse than i imagined... also, i forgot that youtube won't accept (from me, at present) vids longer than 10 minutes.  so you missed the update of my feet.  have no fear, we'll capture some beauty shots of those things at the end of my legs.

"this love is stronger..."

Dominic Balli - Daisy's Song Live 2012

Published on Mar 30, 2012

by dominicballi

When that storm comes
Like a hurricane
And the sun seems far away

We will not fear the wind
We will not fear the waves
I can feel your calm within

When this life is shaken
By ragin' seas
We are not gon' be afraid

So if ya walk on waves and wind
Then hold my hand and I'll walk again

This love is stronger than the blood that beats my heart
This love is deeper, than the pain of all these scars
This love goes farther than the hope in answer's arms
This love is stronger
It's strong enough for me

You lived our sorrows,
Befriended all our pain
All that we might rise again

You stole my sickness,
Rested in my disease
All that I might rest in thee

And you alone bring healing,
And for you I'll wait
But we are not gon' be afraid


This love is stronger than the blood that beats my heart
This love is deeper, than the pain of all these scars
This love goes farther than the hope in answer's arms
This love is stronger
It's strong enough for me


We may be crushed but we are not ever forsaken
We may be struck down but we are not ever destroyed
Then when that fire comes to shine through me your glory
We are not gonna be afraid

Maniacal Laughter: "these patients' quality of life remains amongst the lowest reported in medical conditions"

Autoimmun Rev. 2012 Dec 6.

Complex regional pain syndrome, prototype of a novel kind of autoimmune disease.


Goebel A, Blaes F.

Pain Research Institute, Department of Translational Medicine, Liverpool University, Liverpool, UK; The Walton Centre NHS Foundation Trust, Liverpool, UK. Electronic address: andreasgoebel@rocketmail.com.

Abstract
Complex regional pain syndrome (CRPS) is a painful condition, which arises in a limb after trauma. CRPS can profoundly affect patients' quality of life, and there is no cure. CRPS is associated with limb-confined sensory, motor, skin, bone and autonomic abnormalities. Recent research has shown that some patients respond to treatment with immunoglobulins, and that a majority have IgG serum-autoantibodies directed against, and activating autonomic receptors. CRPS serum-IgG, when transferred to mice elicits abnormal behaviour. These results suggest that CRPS is associated with an autoantibody-mediated autoimmune process in some cases. CRPS has unusual features, including a non-destructive, and regionally-confined course. We propose that CRPS constitutes a prototype of a new kind of autoimmunity, which we term 'IRAM' (injury-triggered, regionally-restricted autoantibody-mediated autoimmune disorder with minimally-destructive course). Understanding autoimmune contribution to CRPS should allow the exploration of novel treatment modalities in the future. Additional 'functional' disorders, painful or painless may be autoimmune in nature.

*********************          *********************          *********************

The article is available in full text HERE.  Here's the début:

1. Introduction
Around the time when Paul Ehrlich described ‘horror autotoxicus’, the postulate that our body does not tolerate an immune reaction against itself, Paul Sudeck reported on a peculiar painful post-traumatic condition [1] and [2] (Weir Mitchell had first described in 1864, what was later recognized as a post-nerve injury form of the same condition; this rare subgroup is now classified as ‘CRPS II’; Mitchell had termed the condition ‘causalgia’ after the reported peculiar, burning pain). In 1900, Sudeck portrayed five patients admitted to the General Hospital in Hamburg, Germany, who had sustained peripheral limb trauma and developed disproportionate, un-abiding limb pain, associated with limb-confined swelling, sweating and reddening. He initially considered that these signs and symptoms were caused by a particular inflammatory reaction. He identified localized osteoporosis on X-ray and thus assigned the term ‘acute, entzuendliche Knochenatrophy’ (acute inflammatory bone atrophy). This syndrome subsequently received a number of additional names including ‘Sudeck's atrophy’ and ‘Reflex Sympathetic Dystrophy’, until in 1994 ‘complex regional pain syndrome’ (CRPS) was accepted [3]. The diagnostic ‘Budapest’ criteria are based on the presence of pain and certain limb abnormalities including sensory, autonomic, trophic and motor changes [4]. CRPS is costly to both the healthcare system and society. Only few patients with un-abiding CRPS return to work [5]. There are only few treatments, and there is no cure [6] and [7]. The condition has continued to puzzle investigators. Bizarre aspects of its presentation have continued to emerge over the past 110 years, and although we now understand that CRPS is indeed associated with an initial local inflammatory response – without reported neutrophil invasion or overt tissue destruction [8] – the underlying cause has remained elusive. Over the course of the disease, initial limb signs generally mellow [9], however about 15% of patients continue to have unrelenting pain [5]; these patients' quality of life remains amongst the lowest reported in medical conditions [6].

We propose that in some cases CRPS is autoimmune-mediated, caused by a novel kind of autoimmunity, which has unusual features. One important feature is, that CRPS is post-traumatic, and that certain parts of the body – the peripheral limbs – are susceptible [10]. Stable regional restriction of autoimmunity within a larger organ is rare; it occurs, for example in ophiasis, an occipital form of alopecia areata, which is T-cell mediated [11]. A ‘two-hit’ process may explain a regional restriction. Pre-existing circulating autoantibodies (the ‘first hit’) may become pathogenic only in the context, and around the area of regional trauma (the second hit, Fig. 1A). Peripheral limbs may provide a facilitating environment. One additional unusual CRPS feature is minimal tissue destruction, even after many years disease duration. Other CRPS characteristics accord with a ‘classical’ autoimmune presentation. CRPS is usually of adult onset [12]. There are HLA associations, although most studies have been small [13]. A number of investigators have described cases following viral and bacterial infections [14] and [15]; further we have provided preliminary serological evidence for antecedent infections with chlamydia, parvovirus and campylobacter [16], [17] and [18].

::rocking::on::the::water::

Back on December 16, 2012, Daisy's Dad tweeted: "Scan results are in & apart from God's supernatural intervention Daisy’s prognosis is bleak."

Three days ago, the Pray For Daisy website blog reported:

Difficult day
Today is a difficult day for Daisy… with large tumors in her abdomen and trying to recover from two weeks of chemotherapy, her body is struggling. She is extremely fragile and weak.
[followed by an invitation to prayer and fast]
Tyler Morgan
Executive Director
The Daisy Merrick Trust

Daisy and her father Britt

Last night I dreamed about surfing, and, trust me, surfing is not in my repertoire, not even in my impressive and intrepid athletic Days of Yore.  Daisy comes from a surfing family, a surfing heritage. Her grandfather, Al Merrick, is a famed "shaper."

Professionals and amateurs alike have "paddled for Daisy" all over the world...  And so my dreams and my heart are telling me to tell you that and to show you Daisy, and other similar souls, rocking on the water.

Maui, HI
Launiupoko, Maui, HI

Honolulu, HI
Diamond head side of the Hilton Hawaiian pier

North Shore, HI
Ehukai Beach Park and paddle to Waimea Bay

Pacifica, CA
Linda Mar Beach (South side of the beach)

Santa Cruz, CA
Location: Cowells Beach
(north side of the pier in front of the Dream Inn)

Carmel Beach, CA
Bottom of 13th St at Carmel Beach

Pismo Beach, CA
South Side of the Pismo Beach Pier

Santa Barbara, CA
Santa Claus Lane Beach (southside)

Oxnard, CA
Oxnard Shores – 5th St.

South Bay, CA
EL Porto (45th St)

Huntington Beach, CA
HB Pier (South Side)

Newport Beach, CA
Newport Beach Pier (South Side)

San Clemente, CA
The San Clemente Pier

Oceanside, CA
Oceanside Pier, South Side (200 The Strand)

Encinitas, CA
Moonlight Beach

Minneapolis, MN
Lake Calhoun North Beach West Lake Street

Rockaway Beach, NY
Rockaway Beach 90th St, NY

Manasquan/ Spring Lake, NJ
Ocean Ave and Pitney Ave (by the Arches)

Virginia Beach, VA
1st street jetty

Avon, NC
Avon Pier

Surf City, NC
Kinston Street Beach Access next to the pier

Emerald Isle, NC
Bogue Inlet Pier

Wrightsville Beach, NC
Oceanic Street (Access #28)

Carolina Beach, NC
Hamlet Ave Access

North Myrtle Beach, SC
Cherry Grove Pier, 3500 North Ocean Boulevard

Myrtle Beach, SC
Myrtle Beach State Park
4401 South Kings Hwy Myrtle Beach, SC

Charleston, SC
The Washout

Jacksonville, FL
Jacksonville Pier

St. Augustine, FL
FA’s at the North side of St. Augustine Pier

Ormond Beach, FL
Granada approach, A1A at Granada Bvd. (SR-40)

New Smyrna Beach, FL
Flagler Ave. Beach ramp(on the beach)

Flagler Beach, FL
South Sixth St.

Melbourne Beach, FL
Ocean Avenue (beach access)

Deerfield Beach, FL
Deerfield Beach Pier

Panama City, FL
Panama City Beach Pier

daisy surfing

Fort Worth, TX

Kuta Bali
Pantai Kuta, Jl. Pantai Kuta, Kuta 80361


All photos are property of Al Merrick, Daisy's grandfather, from his company website, Channel Islands Surfboards by Al Merrick.  I have a feeling there's no finer place to satisfy your surfing needs...



FLOW from Koastal Media on Vimeo.

"The story focuses on Channel Islands Surfboards founder and world-renowned surfboard craftsman Al Merrick and his special relationships with the team of world champion Channel Islands Team riders and arguably the two best and most influential surfers ever: Kelly Slater (6 time world champion) and Tom Curren (3 time world champion)."

we do it everyday

Brett Dennen - Ain't No Reason (Official Single Video)

There ain't no reason things are this way.

It's how they always been and they intend to stay.

I can't explain why we live this way.

We do it every day.

Preachers on the podium speaking of saints.

Prophets on the sidewalk begging for change.

Old ladies laughing from the fire escape,

Cursing my name.

I gotta a basket full of lemons and they all taste the same,

A window and a pigeon with a broken wing,

You can spend your whole life working for something,

Just to have it taken away.

People walk around pushing back their debts,

Wearing paychecks like necklaces and bracelets,

Talking about nothing, not thinking about death,

Every little heartbeat, every little breath.

People walk a tightrope on a razors edge.

Carrying their hurt and hatred and weapons.

It could be a bomb, or a bullet, or a pen,

Or a thought, or a word, or a sentence.

There ain't no reason things are this way.

Its how they've always been and they intend to stay.

I don't know why I say the things I say,

But I say them anyway.

But love will come set me free.

Love will come set me free, I do believe.

Love will come set me free, I know it will.

Love will come set me free, yes.

Prison walls still standing tall.

Some things never change at all.

Keep on building prisons, gonna fill them all.

Keep on building bombs, gonna drop them all.

Working your fingers bare to the bone.

Breaking' your back, make you sell your soul.

Like a lung, it's filled with coal,

Suffocating slow.

The wind blows wild and I may move.

But politicians lie and I am not fooled.

You don't need no reason or a three piece suit,

To argue the truth.

The air on my skin and the world under my toes

Slavery stitched into the fabric of my clothes

Chaos and commotion wherever I go,

Love I try to follow.

Love will come set me free

Love will come set me free, I do believe

Love will come set me free, I know it will

Love will come set me free, yes

There ain't no reason things are this way.

Its how they've always been and they intend to stay.

I can't explain why we live this way.

We do it every day.

From Pete Souza, White House Photographer

The Year in Photographs 2012 by White House Photographer Pete Souza

83 Photos You Don't Want to Miss:
By all accounts it's been a historic year at the White House, and we're excited to share some of our favorite photos from behind the scenes in 2012. The White House Photo Office compiled some of the year's best, with commentary from Chief Official White House Photographer Pete Souza.

This is still my favorite, but it dates from 2009.  I just thought this the perfect moment to slip it in.

From Polichicks:  "Pat the President":

This young brother is really feeling the president's fade 

President Obama bends over to let the young son of a White House staffer touch his hair, because the child wants to see if the president's hair feels just like his own.

For the first time in our history, an African American child visiting the White House can see that someone with hair (and skin) like his (or hers) can be anything he wants to be when he grows up - even president of the United States of America.  It's amazing to see that what an Obama presidency means for African Americans - inclusion, representation, unlimited dreams and long awaited, hard fought for change - is not lost on a child this small.

More from Pete Souza:  The Rise of Barack Obama, The Road to Kabul, Wrigley Field, Portrait of a President, Plebe Summer, President Reagan's Funeral

How Pete Souza became President Obama’s secret weaponPosted by Chris Cillizza on December 19, 2012 at 1:08 pmWashington Post 

You probably have never heard of Pete Souza. 

But, Souza, the White House official photographer, plays an absolutely critical — and often under-estimated — role in the shaping of “Barack Obama”, the image of the president presented to the public. 

And, in an election in which Obama’s likability seemed to trump policy concerns that many voters held about him, it’s not an exaggeration to say that Souza was a major cog in the machine  that got the incumbent re-elected. 

“When these eight years are done, Pete will be its most important illustrator,” said Robert Gibbs, who served as White House press secretary in Obama’s first term. [read the rest HERE].

Topical Treatments to Reduce Allodynia in Rat Models of CRPS

CREDIT: Rats have feelings too

The Journal of Pain
Volume 14, Issue 1, Pages 66-78, January 2013


Topical Combinations Aimed at Treating Microvascular Dysfunction Reduce Allodynia in Rat Models of CRPS-I and Neuropathic Pain


J. Vaigunda Ragavendran, André Laferrière, Wen Hua Xiao, Gary J. Bennett, Satyanarayana S.V. Padi, Ji Zhang, Terence J. Coderre*

*Contact for reprint requests


Abstract
Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle, or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either α2-adrenergic (α2A) receptor agonists or nitric oxide (NO) donors combined with either phosphodiesterase (PDE) or phosphatidic acid (PA) inhibitors would effectively reduce allodynia in these animal models of chronic pain. Single topical agents produced significant dose-dependent antiallodynic effects in rats with chronic postischemia pain, and the antiallodynic dose-response curves of PDE and PA inhibitors were shifted 2.5- to 10-fold leftward when combined with nonanalgesic doses of α2A receptor agonists or NO donors. Topical combinations also produced significant antiallodynic effects in rats with sciatic nerve injury, painful diabetic neuropathy, and chemotherapy-induced painful neuropathy. These effects were shown to be produced by a local action, lasted up to 6 hours after acute treatment, and did not produce tolerance over 15 days of chronic daily dosing. The present results support the hypothesis that allodynia in animal models of CRPS-I and neuropathic pain is effectively relieved by topical combinations of α2A or NO donors with PDE or PA inhibitors. This suggests that topical treatments aimed at improving microvascular function may reduce allodynia in patients with CRPS-I and neuropathic pain.

Perspective
This article presents the synergistic antiallodynic effects of combinations of α2A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest that effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected areas.


NOTE:  It may seem odd to publish the references without providing access to the article text, but many is the time I have found helpful background reading among footnoted/referenced sources. It takes some digging, but can pay off in greater understanding and finding your own "leads" within your particular research interests.

References 

1. Agrawal RP, Choudhary R, Sharma P, Sharma S, Beniwal R, Kaswan K, et al. Glyceryl trinitrate spray in the management of painful diabetic neuropathy: A randomized double blind placebo controlled cross-over study. Diabetes Res Clin Pract.2007;77:161–177
   • Abstract
   • Full Text
   •  Full-Text PDF (254 KB) 
   • CrossRef
2. Basile S, Khalil Z, Helme RD. Skin vascular reactivity to the neuropeptide substance P in rats with peripheral mononeuropathy. Pain. 1993;52:217–222
   • Abstract
   •  Full-Text PDF (724 KB) 
   • CrossRef
3. Bassirat M, Helme RD, Khalil Z. Effect of chronic sciatic nerve lesion on the neurogenic inflammatory response in intact and acutely injured denervated rat skin. Inflamm Res. 1996;45:380–385
   • MEDLINE
   • CrossRef
4. Baumhaekel M, Scheffler P, Boehm M. Use of tadalafil in a patient with a secondary Raynaud's phenomenon not responding to sildenafil. Microvasc Res. 2005;69:178–179
   • MEDLINE
   • CrossRef
5. Berger CC, Bokemeyer C, Schneider M, Kuczyk MA, Schmoll HJ. Secondary Raynaud's phenomenon and other late vascular complications following chemotherapy for testicular cancer. Eur J Cancer. 1995;31A:2229–2238
   • MEDLINE
6. Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988;33:87–107
   • Abstract
   •  Full-Text PDF (2172 KB) 
   • CrossRef
7. Bhat VB, Madyastha KM. Antioxidant and radical scavenging properties of 8-oxo derivatives of xanthine drugs pentoxifylline and lisofylline. Biochem Biophys Res Commun. 2001;288:1212–1217
   • CrossRef
8. Böger RH, Bode-Böger SM. Endothelial dysfunction in peripheral arterial occlusive disease: From basic research to clinical use. Vasa. 1997;26:180–184
   • MEDLINE
9. Brown MB. Dermal and Transdermal Drug Delivery Systems: Current and Future Prospects. Drug Delivery. 2006;13:175–187
   • MEDLINE
   • CrossRef
10. Campbell CM, Kipnes MS, Stouch BC, Brady KL, Kelly M, Schmidt WK, et al. Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy. Pain. 2012;153:1815–1823
    • Abstract
    • Full Text
    •  Full-Text PDF (741 KB) 
    • CrossRef
11. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994;53:55–63
    • MEDLINE
    • CrossRef
12. Chen M, Yang Z, Wu R, Nadler JL. Lisofylline, a novel antiinflammatory agent, protects pancreatic beta-cells from proinflammatory cytokine damage by promoting mitochondrial metabolism. Endocrinology. 2002;143:2341–2348
    • MEDLINE
    • CrossRef
13. Cocco G, Strozzi C, Haeusler G, Chu D, Amrein R, Padovan GC. The therapeutic value of clonidine in patients with coronary heart disease. Eur J Cardiol. 1979;10:221–228
    • MEDLINE
14. Coderre TJ, Xanthos DN, Francis L, Bennett GJ. Chronic post-ischemia pain (CPIP): A novel animal model of complex regional pain syndrome-type I (CRPS-I; reflex sympathetic dystrophy) produced by prolonged hind paw ischemia and reperfusion in the rat. Pain. 2004;112:94–105
    • Abstract
    • Full Text
    •  Full-Text PDF (493 KB) 
    • CrossRef
15. Coon ME, Diegel M, Leshinsky N, Klaus SJ. Selective pharmacologic inhibition of murine and human IL-12-dependent Th1 differentiation and IL-12 signaling. J Immunol. 1999;163:6567–6574
    • MEDLINE
16. Courteix C, Bardin M, Chantelauze C, Lavarenne J, Eschalier A. Study of the sensitivity of the diabetes-induced pain model in rats to a range of analgesics. Pain. 1994;57:153–160
    • Abstract
    •  Full-Text PDF (1004 KB) 
    • CrossRef
17. Cubeddu LX. New alpha 1-adrenergic receptor antagonists for the treatment of hypertension: Role of vascular alpha receptors in the control of peripheral resistance. Am Heart J. 1988;116:133–162
    • MEDLINE
    • CrossRef
18. Davis KD, Treede RD, Raja SN, Meyer RA, Campbell JN. Topical application of clonidine relieves hyperalgesia in patients with sympathetically maintained pain. Pain. 1991;47:309–317
    • Abstract
    •  Full-Text PDF (793 KB) 
    • CrossRef
19. Dawson DL, Cutler BS, Hiatt WR, Hobson RW, Martin JD, Bortey EB, et al. A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med. 2000;109:523–530
    • Abstract
    • Full Text
    •  Full-Text PDF (137 KB) 
    • CrossRef
20. Di Cesare Mannelli L, Zanardelli M, Failli P, Ghelardini C. Oxaliplatin-induced neuropathy: Oxidative stress as pathological mechanism. Protective effect of silibinin. J Pain. 2012;13:276–284
    • Abstract
    • Full Text
    •  Full-Text PDF (863 KB) 
    • CrossRef
21. Doupis J, Lyons TE, Wu S, Gnardellis C, Dinh T, Veves A. Microvascular reactivity and inflammatory cytokines in painful and painless peripheral diabetic neuropathy. J Clin Endocrinol Metab. 2009;94:2157–2163
    • CrossRef
22. Doyle T, Chen Z, Muscoli C, Bryant L, Esposito E, Cuzzocrea S, et al. Targeting the overproduction of peroxynitrite for the prevention and reversal of paclitaxel-induced neuropathic pain. J Neurosci. 2012;32:6149–6160
    • CrossRef
23. Du C, Cooper JC, Klaus SJ, Sriram S. Amelioration of CR-EAE with lisofylline: Effects on mRNA levels of IL-12 and IFN-gamma in the CNS. J Neuroimmunol. 2000;110:13–19
    • Abstract
    • Full Text
    •  Full-Text PDF (424 KB) 
    • CrossRef
24. Dunbar JC, Reinholt L, Henry RL, Mammen E. Platelet aggregation and disaggregation in the streptozotocin induced diabetic rat: The effect of sympathetic inhibition. Diabetes Res Clin Pract. 1990;9:265–272
    • MEDLINE
    • CrossRef
25. Duthie DJ, Nimmo WS. Adverse effects of opioid analgesic drugs. Br J Anaesth. 1987;59:61–77
    • MEDLINE
26. Ferry JJ, Shepard JH, Szpunar GJ. Relationship between contact time of applied dose and percutaneous absorption of minoxidil from a topical solution. J Pharm Sci. 1990;79:483–486
    • MEDLINE
    • CrossRef
27. Giessler C, Wangemann T, Silber RE, Dhein S, Brodde OE. Noradrenaline-induced contraction of human saphenous vein and human internal mammary artery: Involvement of different alpha-adrenoceptor subtypes. NS Arch Pharmacol.2002;366:104–109
28. Goris RJA. Conditions associated with impaired oxygen extraction. In:  Guitierrez G,  Vincent JL editor. Tissue Oxygen Utilization. Berlin, DE: Springer Verlag; 1991;p. 350–369
29. Goris RJA. Reflex sympathetic dystrophy: Model of a severe regional inflammatory response syndrome. World J Surg.1998;22:197–202
    • MEDLINE
    • CrossRef
30. Gorizontova MP, Mironova IV. Microcirculatory changes during the long-term course of deafferentation pain syndrome.Biull Eksp Biol Med. 1993;115:233–236
    • MEDLINE
31. Gorizontova MP, Mironova IV. The effect of prophylactic administration of pentoxifylline (trental) on development of a neuropathic pain syndrome and microcirculatory disorders caused by it. Biull Eksp Biol Med. 1995;119:485–487
    • MEDLINE
32. Groeneweg G, Niehof S, Wesseldijk F, Huygen FJ, Zijlstra FJ. Vasodilative effect of isosorbide dinitrate ointment in complex regional pain syndrome type 1. Clin J Pain. 2008;24:89–92
    • CrossRef
33. Guidot DM, Bursten SL, Rice GC, Chaney RB, Singer JW, Repine AJ, et al. Modulating phosphatidic acid metabolism decreases oxidative injury in rat lungs. Am J Physiol. 1997;273:L957–L966
    • MEDLINE
34. Hasegawa N, Oka Y, Nakayama M, Berry GJ, Bursten S, Rice G, et al. The effects of post-treatment with lisofylline, a phosphatidic acid generation inhibitor, on sepsis-induced acute lung injury in pigs. Am J Respir Crit Care Med.1997;155:928–936
35. Heerschap A, den Hollander JA, Reynen H, Goris RJ. Metabolic changes in reflex sympathetic dystrophy: A 31P NMR spectroscopy study. Muscle Nerve. 1993;16:367–373
    • CrossRef
36. Heyneman CA, Lawless-Liday C, Wall GC. Oral versus topical NSAIDs in rheumatic diseases: A comparison. Drugs.2000;60:555–574
    • MEDLINE
    • CrossRef
37. Higa M, Takasu N, Tamanaha T, Nakamura K, Shimabukuro M, Sasara T, et al. Nitroglycerin spray rapidly improves pain in a patient with chronic painful diabetic neuropathy. Diabet Med. 2004;21:1053–1054
    • MEDLINE
    • CrossRef
38. Horlington M, Watson PA. Inhibition of 3'5'-cyclic-AMP phosphodiesterase by some platelet aggregation inhibitors. Biochem Pharmacol. 1970;19:955–956
    • MEDLINE
    • CrossRef
39. Hrometz SL, Edelmann SE, McCune DF, Olges JR, Hadley RW, Perez DM, et al. Expression of multiple alpha1-adrenoceptors on vascular smooth muscle: Correlation with the regulation of contraction. J Pharmacol Exp Ther. 1999;290:452–463
    • MEDLINE
40. Hyland WT. Treating reflex sympathetic dystrophy with transdermal nitroglycerin. Plast Reconstr Surg. 1989;83:195
    • MEDLINE
    • CrossRef
41. Ignarro LJ, Napoli C, Loscalzo J. Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide: An overview. Circ Res. 2002;90:21–28
    • CrossRef
42. Inkster ME, Cotter MA, Cameron NE. Treatment with the xanthine oxidase inhibitor, allopurinol, improves nerve and vascular function in diabetic rats. Eur J Pharmacol. 2007;561:63–71
    • MEDLINE
    • CrossRef
43. Insel J, Halle AA, Mirvis DM. Efficacy of pentoxifylline in patients with stable angina pectoris. Angiology. 1988;39:514–519
    • MEDLINE
    • CrossRef
44. Jacoby D, Mohler ER. Drug treatment of intermittent claudication. Drugs. 2004;64:1657–1670
    • MEDLINE
    • CrossRef
45. Jin HY, Lee KA, Song SK, Liu WJ, Choi JH, Song CH, et al. Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats. Eur J Pharmacol. 2012;674:217–226
    • CrossRef
46. Jin SM, Noh CI, Yang SW, Bae EJ, Shin CH, Chung HR, et al. Endothelial dysfunction and microvascular complications in type 1 diabetes mellitus. J Korean Med Sci. 2008;23:77–82
    • CrossRef
47. Khalil Z, Liu T, Helme RD. Free radicals contribute to the reduction in peripheral vascular responses and the maintenance of thermal hyperalgesia in rats with chronic constriction injury. Pain. 1999;79:31–37
    • Abstract
    • Full Text
    •  Full-Text PDF (133 KB) 
    • CrossRef
48. Kihara M, Schmelzer JD, Low PA. Effect of cilostazol on experimental diabetic neuropathy in the rat. Diabetologia.1995;38:914–918
    • CrossRef
49. Kirchmair R, Walter DH, Ii M, Rittig K, Tietz AB, Murayama T, et al. Antiangiogenesis mediates cisplatin-induced peripheral neuropathy: Attenuation or reversal by local vascular endothelial growth factor gene therapy without augmenting tumor growth. Circulation. 2005;111:2662–2670
    • CrossRef
50. Kirchmair R, Tietz AB, Panagiotou E, Walter DH, Silver M, Yoon YS, et al. Therapeutic angiogenesis inhibits or rescues chemotherapy-induced peripheral neuropathy: Taxol- and thalidomide-induced injury of vasa nervorum is ameliorated by VEGF. Mol Ther. 2007;15:69–75
    • MEDLINE
    • CrossRef
51. Koban M, Leis S, Schultze-Mosgau S, Birklein F. Tissue hypoxia in complex regional pain syndrome. Pain. 2003;104:149–157
    • Abstract
    • Full Text
    •  Full-Text PDF (205 KB) 
    • CrossRef
52. Kokesh J, Kazmers A, Zierler RE. Pentoxifylline in the nonoperative management of intermittent claudication. Ann Vasc Surg.1991;5:66–70
    • Abstract
    •  Full-Text PDF (478 KB) 
    • CrossRef
53. Kukushkin ML, Smirnova VS, Gorizontova MP, Mironova IV, Zinkevich VA. Effect of clofelin and propranolol on the development of neurogenic pain syndrome in rats. Patol Fiziol Eksp Ter. 1993;4:16–19
    • MEDLINE
54. Kumar N, Laferriere A, Yu JSC, Leavitt A, Coderre TJ. Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. J Neurochem. 2010;113:552–561
    • CrossRef
55. Kurita GP, Pimenta CA. Compliance with chronic pain treatment: Study of demographic, therapeutic and psychosocial variables. Arq Neuropsiquiatr. 2003;61:416–425
    • CrossRef
56. Laferrière A, Millecamps M, Xanthos DN, Xiao WH, Siau C, de Mos M, et al. Cutaneous tactile allodynia associated with microvascular dysfunction in muscle. Mol Pain. 2008;4:49
    • CrossRef
57. Lekakis JP, Papamichael CM, Vemmos CN, Voutsas AA, Stamatelopoulos SF, Moulopoulos SD. Peripheral vascular endothelial dysfunction in patients with angina pectoris and normal coronary arteriograms. J Am Coll Cardiol. 1998;31:541–546
    • Abstract
    • Full Text
    •  Full-Text PDF (119 KB) 
    • CrossRef
58. Li C, Sekiyama H, Hayashida M, Takeda K, Sumida T, Sawamura S, et al. Effects of topical application of clonidine cream on pain behaviors and spinal Fos protein expression in rat models of neuropathic pain, postoperative pain, and inflammatory pain. Anesthesiology. 2007;107:486–494
    • CrossRef
59. Lincoln TM. Cyclic GMP and mechanisms of vasodilation. Pharmacol Ther. 1989;41:479–502
    • MEDLINE
    • CrossRef
60. Liu J, Feng X, Yu M, Xie W, Zhao X, Li W, et al. Pentoxifylline attenuates the development of hyperalgesia in a rat model of neuropathic pain. Neurosci Lett. 2007;412:268–272
    • MEDLINE
    • CrossRef
61. Magnusson M, Bergstrand IC, Björkman S, Heijl A, Roth B, Höglund P. A placebo-controlled study of retinal blood flow changes by pentoxifylline and metabolites in humans. Br J Clin Pharmacol. 2006;61:138–147
    • MEDLINE
    • CrossRef
62. Magnusson M, Gunnarsson M, Berntorp E, Björkman S, Höglund P. Effects of pentoxifylline and its metabolites on platelet aggregation in whole blood from healthy humans. Eur J Pharmacol. 2008;581:290–295
    • CrossRef
63. Manahan AP, Burkman KA, Malesker MA, Benecke GW. Clinical observation on the use of topical nitroglycerin in the management of severe shoulder-hand syndrome. Nebr Med J. 1993;78:87–89
    • MEDLINE
64. Matsumura H, Jimbo Y, Watanabe K. Haemodynamic changes in early phase reflex sympathetic dystrophy. Scandinavian J Plast Reconstr Surg Hand Surg. 1996;30:133–138
65. Mazoit JX. Conventional techniques for analgesia: Opioids and non-opioids. Indications, adverse effects and monitoring.Ann Fr Anesth Reanim. 1998;17:573–584
    • MEDLINE
    • CrossRef
66. Messin R, Fenyvesi T, Carreer-Bruhwyler F, Crommen J, Chiap P, Hubert P, et al. A pilot double-blind randomized placebo-controlled study of molsidomine 16 mg once-a-day in patients suffering from stable angina pectoris: Correlation between efficacy and over time plasma concentrations. Eur J Clin Pharmacol. 2003;59:227–232
    • MEDLINE
    • CrossRef
67. Millecamps M, Coderre TJ. Rats with chronic post-ischemia pain (CPIP) exhibit an analgesic sensitivity profile similar to human patients with complex regional pain syndrome type I (CRPS-I). Eur J Pharmacol. 2008;583:97–102
    • CrossRef
68. Niehörster M, Schönharting M, Wendel A. A novel xanthine derivative counteracting in vivo tumor necrosis factor alpha toxicity in mice. Circ Shock. 1992;37:270–273
    • MEDLINE
69. Novo S, Abrignani MG, Liquori M, Sangiorgi GB, Strano A. The physiopathology of critical ischemia of the lower limbs. Ann Ital Med Int. 1993;8(Suppl):66S–70S
70. Oka Y, Hasegawa N, Nakayama M, Murphy GA, Sussman HH, Raffin TA. Selective downregulation of neutrophils by a phosphatidic acid generation inhibitor in a porcine sepsis model. J Surg Res. 1999;81:147–155
    • Abstract
    •  Full-Text PDF (114 KB) 
    • CrossRef
71. Palos GR, Mendoza TR, Cantor SB, Aday LA, Cleeland CS. Perceptions of analgesic use and side effects: What the public values in pain management. J Pain Symptom Manage. 2004;28:460–473
    • Abstract
    • Full Text
    •  Full-Text PDF (157 KB) 
    • CrossRef
72. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327:524–526
    • MEDLINE
    • CrossRef
73. Polomano RC, Mannes AJ, Clark US, Bennett GJ. A painful peripheral neuropathy in the rat produced by the chemotherapeutic drug, paclitaxel. Pain. 2001;94:293–304
    • Abstract
    • Full Text
    •  Full-Text PDF (666 KB) 
    • CrossRef
74. Quattrini C, Harris ND, Malik RA, Tesfaye S. Impaired skin microvascular reactivity in painful diabetic neuropathy. Diabetes Care. 2007;30:655–659
    • CrossRef
75. Ragavendran JV, Laferriere A, Khorashadi M, Coderre TJ: The early anti-allodynic effect of pentoxifylline on chronic post-ischemia pain depends on modulation of plantar blood flow. Abstracts of the XIII World Congress on Pain, IASP Press, PT 186, 2010
76. Rice GC, Brown PA, Nelson RJ, Bianco JA, Singer JW, Bursten S. Protection from endotoxic shock in mice by pharmacologic inhibition of phosphatidic acid. Proc Natl Acad Sci USA. 1994;91:3857–3861
77. Robless P, Mikhailidis DP, Stansby GP. Cilostazol for peripheral arterial disease. Cochrane Database Syst Rev. 2007;CD003748
78. Rybalkin SD, Beavo JA. Multiplicity within cyclic nucleotide phosphodiesterases. Biochem Soc Trans. 1996;24:1005–1009
    • MEDLINE
79. Schurmann M, Zaspel J, Grandl G, Wipfel A, Christ F. Assessment of the peripheral microcirculation using computer-assisted venous congestion plethysmography in post-traumatic complex regional pain syndrome type I. J Vasc Res.2001;38:453–461
    • MEDLINE
    • CrossRef
80. Smith RV, Waller ES, Doluisio JT, Bauza MT, Puri SK, Ho I, et al. Pharmacokinetics of orally administered pentoxifylline in humans. J Pharm Sci. 1986;75:47–52
    • MEDLINE
    • CrossRef
81. Spreux-Varoquaux O, Doll J, Dutot C, Grandjean N, Cordonnier P, Pays M, et al. Pharmacokinetics of molsidomine and its active metabolite, linsidomine, in patients with liver cirrhosis. Br J Clin Pharmacol. 1991;32:399–401
    • MEDLINE
    • CrossRef
82. Sternitzky R, Seige K. Clinical investigation of the effects of pentoxifylline in patients with severe peripheral occlusive vascular disease. Curr Med Res Opin. 1985;9:602–610
    • MEDLINE
    • CrossRef
83. Stewart WC. Effect and side effects of apraclonidine. Klin Monatsbl Augenheilkd. 1996;209:A7–A13
84. Suh KS, Oh SJ, Woo JT, Kim SW, Yang IM, Kim JW, et al. Effect of cilostazol on the neuropathies of streptozotocin-induced diabetic rats. Korean J Intern Med. 1999;14:34–40
    • MEDLINE
85. Sztajzel J, Mach F, Righetti A. Role of the vascular endothelium in patients with angina pectoris or acute myocardial infarction with normal coronary arteries. Postgrad Med J. 2000;76:16–21
    • MEDLINE
    • CrossRef
86. Ting JC, Fukshansky M, Burton AW. Treatment of refractory ischemic pain from chemotherapy-induced Raynaud's syndrome with spinal cord stimulation. Pain Pract. 2007;7:143–146
    • CrossRef
87. van der Laan L, ter Laak HJ, Gabreels-Festen A, Gabreels F, Goris RJA. Complex regional pain syndrome type I (RSD): Pathology of skeletal muscle and peripheral nerve. Neurology. 1998;51:20–25
    • MEDLINE
    • CrossRef
88. Van Zwieten PA, Thoolen MJ, Timmermans PB. The pharmacology of centrally acting antihypertensive drugs. Br J Clin Pharmacol. 1983;15(Suppl 4):455S–462S
    • CrossRef
89. Waldman SA, Murad F. Cyclic GMP synthesis and function. Pharmacol Rev. 1987;39:163–196
    • MEDLINE
90. Wattanasirichaigoon S, Menconi MJ, Delude RL, Fink MP. Lisofylline ameliorates intestinal mucosal barrier dysfunction caused by ischemia and ischemia/reperfusion. Shock. 1999;11:269–275
    • MEDLINE
    • CrossRef
91. Waxman K, Daughters K, Aswani S, Rice G. Lisofylline decreases white cell adhesiveness and improves survival after experimental hemorrhagic shock. Crit Care Med. 1996;24:1724–1728
    • MEDLINE
    • CrossRef
92. Weiss B, Hait WN. Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents. Ann Rev Pharmacol Toxicol. 1977;17:441–477
93. Xanthos DN, Bennett GJ, Coderre TJ. Norepinephrine-induced nociception and vasoconstrictor hypersensitivity in rats with chronic post-ischemia pain. Pain. 2008;137:640–651
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