Special Issue! Get Your Special Issue, Right Here!

Oh, the excitement.  Hold me back. 

The current issue of everyone's bedtime reading, Pain Medicine -- The Official Journal of the American Academy of Pain Medicine and of the Faculty of Pain Medicine of the Australian and New Zealand College of Anaesthetists and of the International Spine Intervention Society?

None other than the long awaited Volume 11, Issue 8?

Dated August 1, 2010?

Okay, so it is the "Introduction to CRPS" Special Issue!

No, I am NOT kidding!  Life CAN be unexpectedly exciting and off-the-chart, unimaginably AWESOME!  When you least expect it, just when you thought it would never happen:  A CRPS SPECIAL ISSUE!

I remember the whispers, the muttering, the animalistic vocalizations, the underground rumor that such a thing might happen, one day.

I used to dream of making the cover -- of winning out over the hundreds of other beautiful people with icy, purple extremities and twisted appendages because I, Me, Moi -- I had the iciest, the purplest, the most twisted stuff of them all.  Mwa ha ha!

What?  What?  Did I write that out loud?

In addition to my covergirl fantasy, I confess to a couple of snickers and a near snort -- it just strikes mine ear as funny -- Introduction to CRPS. 

Introduction to CRPS -- Doesn't it sound like one of the evening offerings for the local university extension?

Introduction to Container Gardening! Haiku in a Jiffy!  Cardio Salsa!  Introduction to CRPS!  Intermediate Creative Non-Fiction! Hip Hop for Beginners!

The university closest to Marlinspike Hall puts out a colorful brochure with "What are you waiting for? Begin Your Personal Renaissance today!"  slashed in italic red across the top.

As if that weren't enough to depress me, those Academic Stuffed Shirts (but Marketing Djinni) go on to congratulate themselves for offering "seriously unstuffy adult education... since 1951."  Seriously unstuffy.  Those wackadoodles!  Excuse me while I slap my knee and die laughing.

Okay, I confess.  My breath is bated in anaerobic anticipation for their Personal Renaissance BOGO sale, when, I imagine, the Au Pair Enrichment Program (no, I am not kidding) will kick off with "What to Say When You Talk to Yourself."  It seems that the State Department of Tête de Hergé (très décédé, d'ailleurs) aims to educate the many imported exotic babysitters that litter our domestic landscapes.  In order to successfully obtain a pre-framed Certificate of Completion, our Au Pairs must complete 13 semester hours at an accredited university extension program -- plus $14.95 for the frame, $3.95 extra for matting (hanging hardware included).

Once the Au Pair establishes fluency in the languages and cultures of Tête de Hergé (très décédé, d'ailleurs), s/he is free to use the rest of his or her 13 semester hours to take Personal Enrichment electives.

I checked the credentials for the instructor of this Self Talk course, and she is, indeed, a  "Licensed and Certified Self-Talk Instructor," having attended the famed Self-Talk Institute -- brainchild of Dr. Shad Helmstetter, Ph.D. -- yes, of Scottsdale, Arizona.  That Doctor Helmstetter.

I was pleasantly surprised to find that the good doctor maintains a website where one can purchase CDs of his life-changing Self Talk scripts -- in case you, like me, can't think of a thing to say to yourself and don't have Monday evenings free to audit the Personal Renaissance Au Pair Enrichment Program.  The hallmark of any good webpage -- with just a glance, several pressing questions were answered:  How often do I need to talk to myself?  Are Helmstetter's Self-Talk Scripts the absolute best out there? Are these the last Self-Talk Scripts I will ever have to buy?

He calls them a Lifetime Library -- No more obsessive shushing, no more reading material merely on loan, like at your average library, all those annoying renewals and returns, dealing with snarky middle-aged women sporting pince-nez, going on and on about late fees, and blocking your access to computer porn.

[Not to go off on a tangent, but I wanted to address the wearing of the Pince-Nez, which, as you likely know, is undergoing a revitalization.  You can find the answer to any of your pince-nez related concerns at this useful blog:  Pince-Nez Renaissance,  whose stated purpose is:

To assist those who are interested in wearing pince-nez and promote awareness of this antique eyeglass style. There is very little information available on wearing pince-nez and it is easy to become discouraged. This site, the work of two full-time pince-nez wearers, provides the advice necessary for wearing this distinguished style of eyeglasses.

So it's true -- you can find anything on the internet.  I guess the corollary must work, as well, huh? The internet has room for everyone.  Thank goodness.]

This is the set of Self-Talk CDs that is personally recommended by Dr. Shad Helmstetter — the best Self-Talk ever produced.



Each album includes four complete Self-Talk Sessions — 1 Morning Session, 1 Nighttime Session, and 2 Daytime Sessions — so you’ll have exactly the right Self-Talk morning, daytime, and night.


The best-selling Self-Talk CD program of all time!

Dr. Shad Helmstetter wrote this state-of-the-art set of Self-Talk CDs to be the ultimate self-improvement CDs -- exactly the right Self-Talk that would cover everything - Self-Talk that anyone could use at any time for every situation.


The Lifetime Library is a set of CDs that covers:Self-Esteem; Financial Success; Personal Relationships; Personal Organization; Job and Career; Health and Fitness; Personal Growth; and Quality of Life.


No home should be without this incredible, life-changing library of professionally recorded Self-Talk CDs.

I wish I were equipped with what is necessary for such shameless promotion.  Imagine me in the middle of your telecommunication highway, stopping traffic, wearing a sandwich board advertising Special Issue!  Get Your Special Issue, Today!  CRPS, The Down and Dirty!  Get Your Special CRPS Issue, Today!

What did you expect:  The End is Near?

The Introduction to CRPS Special Issue -- and by this, I mean the introduction, as in the piece doing the introducing, was written by Peter R. Wilson MB, BS, PhD.

What follows is an embarrassment of riches, at least as far as CRPS research is concerned -- solid work by known names in the field -- pioneers, even.   Maybe the best part of all?  There is no evidence of the existence, much less the thought, of that TURD José Ochoa!


Objectification of the Diagnostic Criteria for CRPS - August 1, 2010 (Pain Medicine -- Journal of the American Academy of Pain Medicine)
Author Information:  R. Norman Harden, MD, Rehabilitation Institute of Chicago, 446 E Ontario Street, Suite 1011, Chicago, IL 60611, USA. Tel: 312-238-5654; Fax: 312-238-7624; E-mail: nharden@ric.org.

Abstract:  The current diagnostic criteria for complex regional pain syndrome (CRPS), codified by the International Association for the Study of Pain's taxonomy committee, and newer statistically derived criteria (the “Budapest” criteria), are both deliberately based on bedside testing. Designing criteria that are accessible to any clinician, not requiring any special equipment or training, is very important for clinical diagnosis. However, that approach, albeit pragmatic, forces a very heavy reliance on the subjective (not only the subjective response of the patient, but the subjective impression of the clinician). This is very problematic scientifically and statistically. Fortunately, with some new technologies and new approaches to old technologies, significant improvements can be made not only in terms of quantification, but also in allowing significant objectification of the diagnostic data. We will initiate a discussion of some of these potentially useful approaches.

Plasticity of Complex Regional Pain Syndrome (CRPS) in Children - August 1, 2010 (Pain Medicine)
Author Information:  Michael Stanton-Hicks, MB, BS, Dr. Med, FRCA, ABPM, Pain Management Department, Center for Neurological Restoration, Consulting Staff, Children's Hospital CCF Shaker Campus, Pediatric Pain Rehabilitation Program, Cleveland Clinic, Cleveland, OH 44195 USA. Tel: 261-445-9559; Fax: 216-444-9890; E-mail: stantom@ccf.org.

Abstract:  Complex regional pain syndrome I (CRPS I) is defined by the International Association for the Study of Pain (IASP) criteria to include pain that is disproportionate to the inciting event, sensory disturbances such as allodynia/ hyperalgesia, autonomic dysfunction, and motor dysfunction that usually occurs after trauma that is frequently trivial and generally expressed in an extremity. These symptoms are well described in the adult population, but there are relatively few data or reports of its prevalence in the pediatric population. Recent studies have demonstrated that unlike the adult population, about 90% of the cases reported are females in a range of 8 to 16 years, the youngest being 3 years old. There tends to be delay in recognizing the diagnosis, which may be as long as 4 months. In contrast to adults, the response to treatment, particularly exercise therapy with behavioral management will achieve almost 97% remission. While the pathophysiology is poorly understood, many features, particularly the neurologic abnormalities, suggest both peripheral and central nervous system involvement. Peripheral small fiber neuropathy as an etiology and inflammation involving small nerve fibers (neurogenic inflammatory pain) has been suggested. A tissue inflammatory etiology has been investigated over the past 25 years. However, these inflammatory aspects differ from those seen in other conditions involving tissue inflammation. The suggestion that CRPS in children is a different clinical entity than that seen in the adult, is probably incorrect, as recent evidence would suggest that the pathophysiology is most likely identical involving endocrine, behavioral, developmental, and environmental factors that distinguish clinical presentation in children from the adult. Behavioral management is a mandatory accompaniment of any program of exercise therapy and the sometimes extreme sensory disturbances and parental enmeshment do distinguish the clinical presentation from that in the adult. Interventional procedures may be required in the face of extreme allodynia preventing exercise therapy, and in occasional cases interruption of the sympathetic nerves may reverse this symptom in a few children. Occasionally, continuous analgesia techniques such as that which can be delivered by tunneled epidural catheter or an externalized neurostimulator (spinal cord stimulation) for short periods of time are effective.

A Hypothesis for the Cause of Complex Regional Pain Syndrome-Type I (Reflex Sympathetic Dystrophy): Pain Due to Deep-Tissue Microvascular Pathology
Author Information: Terence J. Coderre, PhD, Anesthesia Research Unit, McGill University, Room 1203, McIntyre Bldg., 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6. Tel: 514-398-5773; Fax: 514-398-8241; E-mail: terence.coderre@mcgill.ca.

Abstract:  Complex regional pain syndrome-type I (CRPS-I; reflex sympathetic dystrophy) is a chronic pain condition that usually follows a deep-tissue injury such as fracture or sprain. The cause of the pain is unknown. We have developed an animal model (chronic post-ischemia pain) that creates CRPS-I-like symptomatology. The model is produced by occluding the blood flow to one hind paw for 3 hours under general anesthesia. Following reperfusion, the treated hind paw exhibits an initial phase of hyperemia and edema. This is followed by mechano-hyperalgesia, mechano-allodynia, and cold-allodynia that lasted for at least 1 month. Light microscopic analyses and electron microscopic analyses of the nerves at the site of the tourniquet show that the majority of these animals have no sign of injury to myelinated or unmyelinated axons. However, electron microscopy shows that the ischemia-reperfusion injury produces a microvascular injury, slow-flow/no-reflow, in the capillaries of the hind paw muscle and digital nerves. We propose that the slow-flow/no-reflow phenomenon initiates and maintains deep-tissue ischemia and inflammation, leading to the activation of muscle nociceptors, and the ectopic activation of sensory afferent axons due to endoneurial ischemia and inflammation.

These data, and a large body of clinical evidence, suggest that in at least a subset of CRPS-I patients, the fundamental cause of the abnormal pain sensations is ischemia and inflammation due to microvascular pathology in deep tissues, leading to a combination of inflammatory and neuropathic pain processes. Moreover, we suggest a unifying idea that relates the pathogenesis of CRPS-I to that of CRPS-II. Lastly, our hypothesis suggests that the role of the sympathetic nervous system in CRPS-I is a factor that is not fundamentally causative, but may have an important contributory role in early-stage disease.

Role of Neuropeptide, Cytokine, and Growth Factor Signaling in Complex Regional Pain Syndrome
Author Information: Wade S. Kingery, MD, Physical Medicine and Rehabilitation Service (117), Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave., Palo Alto, CA 94304, USA. Tel: 650-493-5000 ext 64768; Fax: 650-852-3470; E-mail: wkingery@stanford.edu.

Abstract:
Objective.  Complex regional pain syndrome (CRPS) patients exhibit multiorgan pathology and inflammatory changes after limb trauma. The objective of this study was to identify how neuro-cutaneous signaling is facilitated after fracture and examine how this altered signaling contributes to the development of CRPS-like changes in the injured limb.


Design and Methods.  These studies used a rat tibia fracture model that reliably generates hindpaw warmth, edema, increased spontaneous protein extravasation, allodynia, unweighting, and periarticular bone loss, a symptom complex resembling the vascular, nociceptive, and bone sequelae observed in early CRPS. Substance P (SP)-evoked extravasation responses, EIA and PCR assays, and immunohistochemical techniques were used to evaluate post-fracture up-regulation of neuro-cutaneous inflammatory signaling. A SP NK1 receptor antagonist was used to inhibit CRPS-like changes in the fracture model.

Results.  In the rat fracture model the SP-evoked extravasation and edema responses were enhanced. SP NK1 receptor expression also increased in the microvascular endothelial cells in the fracture hindpaw skin, leading us to postulate that NK1 receptor up-regulation mediates the facilitated extravasation and edema responses observed after SP injection. The NK1 receptor antagonist LY303870 reversed hindpaw warmth, edema, increased vascular permeability, allodynia, and unweighting observed after tibia fracture in rats. There was also increased keratinocyte proliferation and NK1 receptor expression in the fracture hindpaw. Similar to the rat fracture model, we have observed increased epidermal thickness and keratinocyte NK1 expression in skin biopsies from CRPS patients. There was an up-regulation of inflammatory cytokine expression in the rat hindpaw skin and in keratinocytes at 4 weeks post-fracture. These inflammatory mediators appear to play a crucial role in the development of pain behavior after fracture, as we have repeatedly demonstrated that inhibition of cytokine, and NGF signaling prevents the allodynia and attenuates unweighting at 4 weeks post-fracture. LY303870 treatment also reversed post-fracture keratinocyte proliferation, suggesting that SP might be acting as an intermediate mediator in the inflammatory cascade by causing the up-regulation of inflammatory proteins that can directly sensitize nociceptors in the skin and joints.

Conclusions.  Collectively, these data suggest that neuro-cutaneous signaling is up-regulated and can mediate inflammatory changes observed in the hindpaw skin of the fracture rat model and in human CRPS skin. Future translational and clinical studies mapping these inflammatory changes may identify novel therapeutic targets for preventing post-traumatic pain from transitioning into chronic CRPS.

Role of Minimal Distal Nerve Injury in Complex Regional Pain Syndrome-I
Author Information: Anne Louise Oaklander, MD, PhD, Massachusetts General Hospital, 275 Charles St./Warren Bldg. 310, Boston, MA 02114, USA. Tel: 617-726-2000; Fax: 617-726-0473; E-mail: aoaklander@partners.org.


Abstract: Unavailable/ See first page of article online

Sensory Disturbances in Complex Regional Pain Syndrome: Clinical Observations, Autonomic Interactions, and Possible Mechanisms
Author Information: Peter D. Drummond, PhD, School of Psychology, Murdoch University, Perth, Western Australia 6150, Australia. Tel: 61-8-9360-2415; Fax: 61-8-9360-6492; E-mail: P.Drummond@murdoch.edu.au.

Abstract

Objective.  To review mechanisms that might contribute to sensory disturbances and sympathetically-maintained pain in complex regional pain syndrome (CRPS).

Background.  CRPS is associated with a range of sensory and autonomic abnormalities. In a subpopulation of patients, sympathetic nervous system arousal and intradermal injection of adrenergic agonists intensify pain.

Results.  Mechanisms responsible for sensory abnormalities in CRPS include sensitization of primary afferent nociceptors and spinothalamic tract neurons, disinhibition of central nociceptive neurons, and reorganization of thalamo-cortical somatosensory maps. Proposed mechanisms of sympathetically-maintained pain include adrenergic excitation of sensitized nociceptors in the CRPS-affected limb, and interaction between processes within the central nervous system that modulate nociception and emotional responses. Central mechanisms could involve adrenergic facilitation of nociceptive transmission in the dorsal horn or thalamus, and/or depletion of bulbo-spinal opioids or tolerance to their effects.

Conclusions.  Sympathetic neural activity might contribute to pain and sensory disturbances in CRPS by feeding into nociceptive circuits at the site of injury or elsewhere in the CRPS-affected limb, within the dorsal horn, or via thalamo-cortical projections.

Vasomotor Disturbances in Complex Regional Pain Syndrome—A Review
Author Information: Gunnar Wasner, Prof Dr Med, Department of Neurology, and Division of Neurological Pain Research and Therapy, University Clinic of Schleswig-Holstein, Campus Kiel, Schittenhelmstraße 10, 24105 Kiel, Germany. Tel: 49-431-597-8815; Fax: 49-431-597-8530; E-mail: g.wasner@neurologie.uni-kiel.de.

Abstract: Complex regional pain syndromes (CRPS) are characterized by vascular disturbances primary affecting the microcirculation in the distal part of the involved extremity. In the acute stage inhibited sympathetic vasoconstriction and exaggerated neurogenic inflammation driven by central and peripheral mechanisms, respectively, seem to be the major pathophysiological mechanisms inducing vasodilation. During the chronic course of the disease as well as early in some patients vasoconstriction dominates the clinical picture induced by changes in the microcirculation itself such as endothelial dysfunction or vascular hyperreactivity, whereas sympathetic vasoconstrictor activity returns and neurogenic inflammation is less severe. It can be suggested that the interaction between different mechanisms underlying vasomotor disturbances as well as the severity of each single mechanism in the individual patient have a great impact on the variety of the overall clinical picture in CRPS. Irrespective of the underlying pathophysiology, measurements of skin temperature differences between the affected and the contralateral extremity can serve as a diagnostic tool in CRPS, in particular when sensitivity and specificity is increased by considering dynamic alterations in skin temperature asymmetries.

Movement Disorders in Complex Regional Pain Syndrome
Author Information:  Jacobus J. van Hilten, Department of Neurology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, the Netherlands. Tel: 31-71-5262895; Fax: 31-71-5248253; E-mail: J.J.van_Hilten@lumc.nl.

Abstract: About 25% of the patients with complex regional pain syndrome (CRPS) suffer movement disorders, including loss of voluntary control, bradykinesia, dystonia, myoclonus, and tremor. These movement disorders are generally difficult to manage and add considerably to the disease burden. Over the last years, interesting findings have emerged that show how tissue or nerve injury may induce spinal plasticity (central sensitization), which alters sensory transmission and sensorimotor processing in the spinal cord and is associated with disinhibition. These changes, in turn, set the stage for the development of movement disorders seen in CRPS. There are no randomized control studies on the treatment of movement disorders in CRPS but findings from fundamental and clinical research suggest that strategies that enhance the central inhibitory state may benefit these patients.

What Does the Mechanism of Spinal Cord Stimulation Tell Us about Complex Regional Pain Syndrome?
Author Information:  Joshua P. Prager, MD, MS, Center for the Rehabilitation of Pain syndromes (CRPS) at UCLA, Internal Medicine and Anesthesiology, 100 UCLA Medical Plaza, Suite 760, Los Angeles, CA 90095, USA. Tel: 310-264-7246; Fax: 310-882-7005; E-mail: joshuaprager@gmail.com.

Abstract: Spinal cord stimulation (SCS) can have dramatic effects on painful, vascular, and motor symptoms of complex regional pain syndrome (CRPS), but its precise mechanism of action is unclear. Better understanding of the physiologic effects of SCS may improve understanding not only of this treatment modality but also of CRPS pathophysiology.


Effects of SCS on pain perception are likely to occur through activation of inhibitory GABA-ergic and cholinergic spinal interneurons. Increased release of both neurotransmitters has been demonstrated following SCS in animal models of neuropathic pain, with accompanying reductions in pain behaviors. Effects of SCS on vascular symptoms of CRPS are thought to occur through two main mechanisms: antidromic activation of spinal afferent neurons and inhibition of sympathetic efferents. Cutaneous vasodilation following SCS in animal models has been shown to involve antidromic release of calcitonin gene-related peptide and possibly nitric oxide, from small-diameter sensory neurons expressing the transient receptor potential V1 (TRPV1) receptor. The involvement of sympathetic efferents in the effects of SCS has not been studied in animal models of neuropathic pain, but has been demonstrated in models of angina pectoris.

In conclusion, SCS is of clinical benefit in CRPS, and although its mechanism of action merits further elucidation, what little we do know is informative and can partially explain some of the pathophysiology of CRPS.

HAPPY READING!