Sunday, July 29, 2012

Tarlov cysts: Insights by Oaklander

Last night I was up until 1:35 AM, all excited about something I found on twitter, a PainResearchForum interview on patient-centered research with Anne Louise Oaklander, associate professor of neurology at Harvard Medical School in Boston, US, and an attending neurologist at Massachusetts General Hospital, the same place Clifford Woolf works
I have got to say, I love her blunt style!


"My lab developed a model of complex regional pain syndrome type I (CRPS-I), formerly known as reflex sympathetic dystrophy, after discovering that patients with CRPS-I have evidence of peripheral nerve injury. It’s a myth that patients with CRPS-I don’t have nerve injury—most of them have undiagnosed nerve injury. Hardly any among the clinicians who treat CRPS-I patients are nerve experts... 
"Another reason why the nerve injuries in CRPS-I remain unrecognized is that patients often have injuries to small sensory nerve branches that are not routinely tested by nerve conduction study, or partial injuries that involve only a few of the axons. So the injured limb may still work reasonably well, and there will still be sensation in the affected area, giving a misleading impression of no nerve injury. Furthermore, EMG [electromyography] and nerve conduction study, the usual tests for diagnosing nerve injury, are completely insensitive to small-fiber function. Many CRPS-I patients have normal EMG and nerve conduction studies, even in the face of injury and dysfunction of their nociceptive fibers."

See RSD/CRPS: The end of the beginning, open access. 
".. distal axons are exquisitely vulnerable to energy deprivation, so vasodysregulation or inflammation can trigger axonopathy. My working hypothesis is that although specific patients may enter the CRPS rotary from different points, malfunctioning small-fiber axons are central. Somatic and autonomic small-fibers densely innervate and regulate tissues to maintain homeostasis. In CPRS, even subtle axonal injuries appear sufficient to trigger remaining fibers into inappropriate firing and neuropeptide release. This combination suffices to cause chronic pain, vasodysregulation, neurogenic inflammation as well as changes in non-neural innervated tissues. Then, too much or too little small-fiber afferent input can wreak additional havoc among central neurons and glia."

On itch
She has been especially interested in post-herpetic neuropathic itch. See Common Neuropathic Itch Syndromes, open access. 
"The sensation of itch – pruritus in medical terminology – can only be perceived by a few tissues, specifically the skin and superficial mucous membranes such as the conjunctiva. So chronic itch complaints are the province of dermatologists, and indeed they most often signal cutaneous injury or inflammation. However, substantial numbers of patients who complain of disabling chronic itch have no apparent cause in the skin. Many of these patients have systemic or medical causes of itch such as drug reactions, allergic or hypersensitivity syndromes, metabolic or endocrine disorders, or toxins associated with kidney or liver dysfunction. Itch is most likely a small-fiber-mediated protective (nocifensive) sensation like pain." (sic: should be nociception. Also, I think there would be some quibble coming her way about whether "perception" is anything "skin" would be capable of doing.. but still, I think she's brilliant.)

She is investigating noninvasive brain stimulation for neuropathic pain. 

"The technology that is furthest advanced is called transcranial magnetic stimulation, or TMS, which involves using high-strength electromagnets to generate electrical pulses that travel through the skull, dura, and cerebrospinal fluid to trigger action potentials in the cortex. The technique is being used to investigate and treat several neurologic dysfunctions including stroke, movement disorders, and visual problems. TMS has been approved by the FDA [US Food and Drug Administration] for treating major depression. For treating neuropathic pain, it is the motor cortex that is often targeted. It’s not clear if it’s the firing of the motor axons themselves that produce the pain relief or whether it is the second-order synapses affecting the thalamus, for instance. But several clinical trials find TMS is effective for a number of neuropathic pain syndromes and other syndromes that may or may not be neuropathic, including fibromyalgia."

About animal models

"We also work on animal models, but we tend to do the animal models after we have characterized the human condition. The greatest need is not for more animal models; it’s for better characterization of the actual human diseases. One of the problems of animal models is that, because the phenotyping is so rudimentary for many neuropathic pain conditions, it’s not clear how relevant the animal models are. For instance, the chronic constriction injury (CCI) model, the most widely used neuropathic pain model, is a wonderful model, but it doesn’t correspond to any particular human disease. It has both nerve injury and inflammatory components, and it changes over time as the sutures that are used are absorbed. So all of the wonderful studies that are done in CCI… Not to dismiss them, because we have learned a tremendous amount about how the nervous system works from them, but the model corresponds loosely at best to an actual human disease or illness."

Tarlov Cysts
The topic that kept me awake and fascinated late into the night is her insight into Tarlov cysts, which I had never heard of before. 

What they are:

"Tarlov cysts... are small cysts that form only on the sensory nerve roots. They form in the arachnoid space that is pulled distally when the cell bodies of primary afferent neurons migrate out of the spinal cord to form the dorsal root ganglia during embryogenesis.
So, in a sense, they are like a minor birth defect. Until they start making trouble. Then they are more like a major birth defect.
"This space allows cerebrospinal fluid to track along the sensory nerve roots through tenuous connections. In some cases, fluid is forced into the neural tissues when intracranial pressure increases (during a cough or bowel movement, for instance), and this gradually causes cysts to form. These cysts in some cases damage the sensory axons and cell bodies in the dorsal root ganglia, and the most common symptom they produce is neuropathic pain."
Wow. It's like the "bulging disc" model, only small, and overlooked by everyone, until she put it together.  
"These perineurial cysts were first described in 1937 by neurosurgeon Isadore Tarlov, who discovered them at autopsy. He had no information about the patients’ symptoms, so he opined in his first paper that they did not cause clinical symptoms. He later treated patients who had these cysts during life and recognized that they are a cause of radiculopathy, much like a herniated disk. But his later papers did not receive adequate attention, because everyone is taught to cite the first paper. So a medical myth was born that Tarlov cysts are irrelevant lesions, and it remains widespread today. In fact, radiologists often see Tarlov cysts on MRIs but don’t report them, because they have been taught these cysts are an incidental finding of no medical significance—just as a dermatologist might not report freckles.
Oh. My. Good. Grief. 

The link to vulvodynia: 
"I learned about Tarlov cysts from patients. My first patient with Tarlov cysts had vulvodynia—pain in the vulva present for decades and often attributed to psychiatric causes. Many treatments had been tried, including vulvar vestibulectomy, or amputation of the outer parts of her vulva, a standard treatment; however, she had never seen a neurologist before me. When I ordered spinal cord imaging, it revealed large Tarlov cysts. At first I had no idea if these were related. Since there was no mention of Tarlov cysts in the textbooks or recent literature, I had to obtain and read the historical papers, which opened my eyes and enabled me to reformulate her illness as neurologic rather than psychiatric.
 She made the crucial link. In her head. She recognized that the woman wasn't necessarily crazy or making up a wild story about pain in her pelvic floor.  
"This is important because Tarlov cysts can be treated and in some cases cured completely using surgical or percutaneous procedures that definitively collapse or remove the cysts, but only if the correct diagnosis is recognized and the clinician knows the treatment options. So Tarlov cysts are a curable cause of painful radiculopathy—and they are not rare, it turns out. But because so few physicians know about them, most patients never get adequate diagnosis and never get treated.
Well, this kinda plops the old "bio" right back into "biopsychosocial" doesn't it? 
"I proposed symposia on Tarlov cysts to be presented at the American Pain Society meeting, and for two years in a row the scientific program committee turned down my request because, they said, no one had ever heard of this, so how important could it be?
"In fact, pain practitioners should welcome this information as they could learn to do the percutaneous CT-guided cyst aspiration, which has been published as an effective and definitive treatment.
They could practice a nice effective operator model, cure patients, and everyone could be more happy, especially patients.  
"Because I am a woman who specializes in neuropathic pain, I was sought out by so many Tarlov cyst patients that it became inescapable for me to make the correct diagnosis and begin to investigate the pathophysiology. In 2010, several colleagues and I published the first paper on Tarlov cysts in the pain literature [Hiers et al, 2010]. A subsequent paper in press in the New England Journal of Medicine describes a detailed study of a nurse who had 21 Tarlov cysts, and despite many medical visits for her chronic neuropathic pain, the cause remained undiagnosed for most of her adult life. When she died unexpectedly of leukemia, I arranged for a very detailed autopsy and neuropathologic study. I hope that once the NEJM paper appears, the pain community will take another look. And I hope that the neurology, neurosurgery, radiology, and gynecology communities will become aware of this disease entity as well so that more patients can get correct diagnosis and treatment. 
"I obtained the world’s first-ever research grant on Tarlov cysts, and we conducted the largest study of radiologically identified cysts, and the first report of cyst symptoms, from a cohort of 500 symptomatic patients. A big part of the problem is that the average Tarlov-cyst patient is a woman with chronic pelvic pain, but the average spine clinician is a man, which has impeded forthright communication needed to establish the link between symptoms and cause.
Face-palm II.
"Some of the patients don’t even mention their pelvic pain and dysfunction, and it’s not a topic that many male physicians feel comfortable asking their female patients about. This has created a “don’t ask, don’t tell” situation that neither side—the clinicians nor the patients—has been able to bridge, to bring this condition to medical and public awareness."
Face-palm III. 

OK, I'm sold. I am going to follow this woman closely, because her insight, into everything persistently painful, everything persistently tormenting in human existence, could be the best thing that has happened to humans, especially female humans, in a very long time. 

There are 95 papers so far, on pubmed, about Tarlov cysts

Here are some with open access. 
1. Jung KT, Lee HY, Lim KJ. Clinical Experience of Symptomatic Sacral Perineural CystKorean J Pain. 2012 Jul;25(3):191-4. Epub 2012 Jun 28.

2. Hur W, Choi SS, Lee JJ. Caudal epidural injections for the treatment of tarlov cysts: suggestions for the better resultsPain Physician. 2012 May-Jun;15(3):E351-353; author reply E353. 

3. Sen RK, Goyal T, Tripathy SK, Chakraborty S. Tarlov cysts: a report of two casesJ Orthop Surg (Hong Kong). 2012 Apr;20(1):87-9. 

4. Freidenstein J, Aldrete JA, Ness T. Minimally invasive interventional therapy for Tarlov cysts causing symptoms of interstitial cystitisPain Physician. 2012 Mar-Apr;15(2):141-6.

5. Smith ZA, Li Z, Raphael D, Khoo LT. Sacral laminoplasty and cystic fenestration in the treatment of symptomatic sacral perineural (Tarlov) cysts: Technical case reportSurg Neurol Int. 2011;2:129. Epub 2011 Sep 27.

6. Kong WK, Cho KT, Hong SK. Symptomatic Tarlov Cyst Following Spontaneous Subarachnoid HemorrhageJ Korean Neurosurg Soc. 2011 Aug;50(2):123-5. Epub 2011 Aug 31.

7. Neulen A, Kantelhardt SR, Pilgram-Pastor SM, Metz I, Rohde V, Giese A. Microsurgical fenestration of perineural cysts to the thecal sac at the level of the distal dural sleeveActa Neurochir (Wien). 2011 Jul;153(7):1427-34; discussion 1434. Epub 2011 May 12.

Tuesday, July 10, 2012

Neural plasticity and rehab - Jeffrey Kleim

A member of SomaSimple, "Elanchaim", found and posted this three-year old video to SomaSimple: 

Enjoy! It's about 1 hr 17 minutes long. At the time, he was at U Florida. 

Highlights of the first 10 minutes: 

1. How neurobiology of the brain changes with damage and how it restores itself.
2. Why we don't have a breakthrough, a "polio vaccine" for stroke: There has been a disconnect between basic sciences and clinical sciences. At almost any university you find speech path, OT and PT departments are completely separate from medical facilities often from basic neurosciences, speak different languages, different journals - huge gap. Also, until just lately, basic sciences haven't really had a whole lot to tell clinical sciences about how they should be doing rehab. 

Definition of Neural Plasticity (minute 4:30)

3. The term "Neuroplasticity" was first coined in the 1800s by psychologist William James: about "habit" he said, "The phenomenon of habit in living beings are due to the plasticity of the organic materials of which their bodies are composed... nervous tissue seems endowed with a very extraordinary degree of plasticity." - William James 1887
4. Research into neural plasticity exploded after about 1995, because of new techniques for investigation.
5. Plasticity begins at level of genome, in genes that seem to be turned on by certain kinds of stimulation; transcriptional products of those gene expressions are proteins which go off in the neurons and impart some kind of change, form new synapses, change connections between neurons. The idea is that this can be manipulated across 100's of millions of neurons.
6. First we must adopt the idea of neural monism, that there is no mind/body problem, no dualism.  

  • "All behaviour, whether it is motor, or sensory, or cognitive, is a product of neural activity."
  • "Changes in behaviour can be observed as changes in neural circuits."

7. Working definition by Kleim, minute 7:50: "Any observable change in neuron structure or function", measurable in several ways; directly by observing individual neurons, or indirectly, inferred from measures across populations of neurons, either anatomically or physiologically.

  • Individual/anatomical: dendritic arborization, spine density, axonal arborization, bouton density, synapse number. 
  • Individual/physiological: unit activity, intrinsic excitability, synaptic currents, axonal bouton density.
  • Population/anatomical: structure weight, structural thickness, structure volume, neuron number, neuron density.
  • Population/physiological: regional blood flow, regional EEG, field EPSPs, sensory representations, motor representations.

Kleim, formerly at U Lethbridge, developed his neural plasticity work at the Greenough Lab in the Beckman Institue in Illinois
“All of my work in graduate school was about how motor learning in an intact nervous system is affected by the way that neurons were connected, looking at plasticity and neural connections,” he said. “I spent most of my graduate career looking at plasticity within motor brain areas and when I left I went on to try and apply that plasticity to a damaged brain, to find out how relearning might be accomplished by the same neuromechanisms that account for learning in a normal brain.”

He currently works as associate professor at the school of Biological and Health Systems Engineering at Arizona State U, in Tempe.
"Jeffrey Kleim studies how neural plasticity supports learning in the intact brain and “relearning” in the damaged or diseased brain. His research is directed at developing therapies that optimize plasticity in order to enhance recovery after stroke and Parkinson’s Disease.The brain is a highly dynamic organ that is capable of structural and functional reorganization in response to a variety of manipulations. This neural plasticity is the mechanism by which the brain encodes experience. My laboratory examines how plasticity within rat and human motor cortex supports learning in the intact brain and “relearning” after stroke. We use intracortical microstimulation in rats and transcranial magnetic stimulation in humans to examine how motor training alters the functional organization of motor cortex. This work has demonstrated that rehabilitation-dependent recovery of motor function after stroke is associated with a reorganization of movement representations in rodent motor cortex. Furthermore, there are specific behavioral and neural signals that drive both recovery and plasticity. These experiments are being used to test novel therapies for enhancing motor recovery in stroke patients."

Here is a list of his publications at PubMed, including these five free ones

1.  Tennant KA, Adkins DL, Donlan NA, Asay AL, Thomas N, Kleim JA, Jones TA. The Organization of the Forelimb Representation of the C57BL/6 Mouse Motor Cortex as Defined by Intracortical Microstimulation and CytoarchitectureCereb Cortex. 2011 April; 21(4): 865–876.
Published online 2010 August 25. doi:  10.1093/cercor/bhq159

2. Tennant KA, Asay AL, Allred RP, Ozburn AR, Kleim JA, Jones TA. The Vermicelli and Capellini Handling Tests: Simple quantitative measures of dexterous forepaw function in rats and miceJ Vis Exp. 2010; (41): 2076. Published online 2010 July 21. doi:  10.3791/2076

3. McHughen SA, Rodriguez PF, Kleim JA, Kleim ED, Marchal Crespo L, Procaccio V, Cramer SC. BDNF Val66Met Polymorphism Influences Motor System Function in the Human Brain. Cereb Cortex. 2010 May; 20(5): 1254–1262. Published online 2009 September 10. doi:  10.1093/cercor/bhp189

4. Kleim JA, Markham JA, Vij K, Freese JL, Ballard DH, Greenough WT. Motor learning induces astrocytic hypertrophy in the cerebellar cortex. Behav Brain Res. Author manuscript; available in PMC 2008 October 29. Published in final edited form as: Behav Brain Res. 2007 March 28; 178(2): 244–249. Published online 2007 January 25. doi:  10.1016/j.bbr.2006.12.022

5. Kleim JA, Freeman JH Jr, Bruneau R, Nolan BC, Cooper NR, Zook A, Walters D. Synapse formation is associated with memory storage in the cerebellumProc Natl Acad Sci U S A. 2002 October 1; 99(20): 13228–13231. Published online 2002 September 16. doi:  10.1073/pnas.202483399 PMCID: PMC130615 Neuroscience

Sunday, July 08, 2012

"Everything you wanted to know about phobias and were afraid to ask" - Gordon Asmundson on fear avoidance

Gordon Asmundson, with students at U of Regina
The second speaker PSD arranged for CPA Congress this spring (see this blogpost for our first, David "Believe in your Placebo"Seminowicz), was Gordon Asmundson, "Ph.D., R. D. Psych, FRSC.. Full Professor of Psychology at the University of Regina, Adjunct Professor of Psychiatry at the University of Saskatchewan, and the leader of a CIHR New Emerging Team focusing on mechanisms and treatment of PTSD", a very prolific researcher with 230 peer-reviewed journal articles (170 of which can be found listed on PubMed), over 50 book chapters, and 6 books. 

His talk was on the need to define important constructs in understanding chronic pain, study models, develop state of the art science, develop treatment options, and examine considerations for the future. The big take-home message: Fear Avoidance (FA) models help explain chronic pain experienced by some people.

The FA model can be generalized to children, attempts to explain how pain relates to anxiety and fear disorders. Pain involves cognitions and emotions as well as sensations. 
Fear differs from anxiety 
1. If a threat is present, fear can fuel escape, which is a defensive behaviour.  
2. Anxiety, however, has more to do with future avoidance, or preventive behaviour.  
3. Both involve threat, both are adaptive; both, however, can become maladaptive. 
Associations between fear/anxiety and pain have been recognized for centuries; it has been learned they have distinct yet overlapping neurobiology. Early key contributors were Fordyce (1976) (1), Letham 1983 (2),  and Philips(1987) (3) [from Asmundson et al, Fear and avoidance in dysfunctional chronic back pain patientsPain 69 (1997) 231–236].

Stimulus is influenced by threat value - e.g., proximity of spider, and threat value really influences the 
response, or salience (Arntz & Claassens 2004)(4). If a subject had been primed to expect "cold", they reported less damage/pain. A significant percentage of people place a high threat value on "pain". High "catastrophizers" overestimated how bad an activity would be (Crombez 2002)(5). All this can result in a downward spiral for these individuals in pain, similar to anxiety disorders. 

Pain experience can go one of two ways: toward confrontation and recovery, or toward avoidance and catastrophizing. (Vlaeyen and Linton 2000)(6). Seeing a headline like "World Death Rate Holding Steady At 100 Percent" (from the Onion, a satirical faux-news publication), will either induce a nod toward an obvious fact, or feed a tendency toward anxiety. Catastrophic headlines are ubiquitous.

Basics of fear and anxiety:
Avoidance feeds high reactivity, disturbs many brain loops. Those with high anxiety and sensitivity can become worried over normal, benign, harmless bodily sensations, such as their own heart beat. Testing individuals for anxiety involves asking for grade on statements, such as, "It's important for me not to appear nervous." A meta-analytic review involving 5,908 participants determined association between anxiety sensitivity and pain (Ocañez 2010)(7).  

The model continues to be tweaked:
Iterations continue (Leeuw 2007)(8). Threatening illness information feeds fear of pain, and avoidance. Some people are predisposed to perceive pain and pain-related arousal as threatening, which leads to escape behaviour. Numerous reviews of the fear avoidance model have appeared, most of which support it. One can use structural equation modeling to ask, Do the models fit the data? - to find out, one can test the pathways in the model (Asmundson and Taylor 1996)(9). Pain intensity and escape behaviour are closely related. A Martin 2010 (PTSD) model fits the data better (10); self-perpetuating cycle holds (Asmundson 2012)(11). 

"Everything you wanted to know about phobias and were afraid to ask"
It makes sense to treat fear and anxieties ahead rather than pain (in chronic pain patients). Establish treatment goals. Educate on the paradox of avoidance behaviours. Avoidance has short term benefits, but in the end is a roller coaster, and does nothing to enhance capacity. But how? Graded exposure. The fear network has to be activated, but just by a little bit. Think of teaching children to swim. Fear of spiders? Expose the patient to the curds, but not the spider. Use reassurance, education, and exercise introduced carefully. Treat the "fear" and the "fear amplifier - "interoceptive exposure". 
Graded in vivo exposure involves a set fear heirarchy, using a standardized set of images. People work through the images, with physiology monitored. The idea is to increase activity without increasing fear and anxiety. Fear declines as avoidance is overcome. When fear declines, so does pain! (Woods and Asmundson 2008)(12). Help patients with interoceptive exposure, to become more familiar with feeling the body changing. There is not a lot of evidence yet, but it appears to work, and is about to be studied more deeply (Watt 2006)(13). 

The model postulates appear to generalize to children, but different assessment tools are needed (Wicksell et al 2005, 08, 09)(14, 15, 16). For children the context is very important; and modelling of pain behaviours must be monitored, for example, modelling by parents. 

In summary:
Context has direct input into fear and anxiety. The model needs to be considered in its broader social context, and psychotherapy approaches such as attention modification, acceptance and mindfulness, etc., adopted.  

Published the same day as Asmundson's presentation: 

1. Fordyce, W.E., Behavioral Methods For Chronic Pain and Illness, Mosby, St. Louis, 1976
2. Letham, J., Slade, P.D., Troup, J.D.G. and Bentley, G., Outline of a fear-avoidance model of exaggerated pain perception - I, Behav. Res.Ther., 21 (1983) 401–408. (no abstract)
3. Philips, H., Avoidance behaviour and its role in sustaining chronic pain, Behav. Res. Ther., 25 (1987) 273–279. (no abstract)
4. Arntz AClaassens L.; The meaning of pain influences its experienced intensityPain. 2004 May;109(1-2):20-5
5. Crombez GEccleston CVan den Broeck AVan Houdenhove BGoubert L.; The effects of catastrophic thinking about pain on attentional interference by pain: no mediation of negative affectivity in healthy volunteers and in patients with low back painPain Res Manag. 2002 Spring;7(1):31-9.
6. Vlaeyen JWLinton SJFear-avoidance and its consequences in chronic musculoskeletal pain: a state of the artPain. 2000 Apr;85(3):317-32.
7. Ocañez KLMcHugh RKOtto MW.; A meta-analytic review of the association between anxiety sensitivity and painDepress Anxiety. 2010 Aug; 27(8):760-7
8. Leeuw MGoossens MELinton SJCrombez GBoersma KVlaeyen JWThe fear-avoidance model of musculoskeletal pain: current state of scientific evidenceJ Behav Med. 2007 Feb;30(1):77-94. Epub 2006 Dec 20.
9. Asmundson GJTaylor SRole of anxiety sensitivity in pain-related fear and avoidanceJ Behav Med. 1996 Dec;19(6):577-86.
10. Anke Ehlers, Oliver Suendermann, Inga Boellinghaus, Anna Vossbeck-Elsebusch, Matthias Gamer, Emma Briddon, Melanie Walwyn Martin, and Edward GlucksmanHeart rate responses to standardized trauma-related pictures in acute posttraumatic stress disorderInt J Psychophysiol. 2010 October; 78(1): 27–34. doi:  10.1016/j.ijpsycho.2010.04.009 (Full Access)
11.  Fetzner MGCollimore KCCarleton RNAsmundson GJ.  Clarifying the relationship between AS dimensions and PTSD symptom clusters: are negative and positive affectivity theoretically relevant constructsCogn Behav Ther. 2012 Mar;41(1):15-25. Epub 2011 Nov 1.
12. Woods MPAsmundson GJ;  Evaluating the efficacy of graded in vivo exposure for the treatment of fear in patients with chronic back pain: a randomized controlled clinical trial. Pain. 2008 Jun;136(3):271-80. Epub 2007 Aug 22.
13. Watt MCStewart SHLefaivre MJUman LS.;  A brief cognitive-behavioral approach to reducing anxiety sensitivity decreases pain-related anxietyCogn Behav Ther. 2006;35(4):248-56.
14. Wicksell RKKihlgren MMelin LEeg-Olofsson O.; Specific cognitive deficits are common in children with Duchenne muscular dystrophy. Dev Med Child Neurol. 2004 Mar;46(3):154-9.
15. Wicksell RKMelin LOlsson GL.; Exposure and acceptance in the rehabilitation of adolescents with idiopathic chronic pain - a pilot studyEur J Pain. 2007 Apr;11(3):267-74. Epub 2006 Apr 17. 

Saturday, July 07, 2012

"Believe in your Placebo" - David Seminowicz

David Seminowicz has been researching the relationship between activity in brain parts, and pain in patients, for a number of years. Building on earlier work by Donald Price, and Catherine Bushnell (among others), he is helping to map out the relationship between cognitive-evaluative, meaning-making parts of the brain, and the sensory-discriminative parts that process raw nociceptive input; together these areas are often termed "the pain matrix"(although that particular term remains contentious). 

He's Canadian, from Toronto originally where he obtained his PhD, won the Next Generation award while at McGill in 2008, contributed to pain research while there. Currently he lives in Maryland and works at the University of Maryland's School of Dentistry.

CPA's Pain Science Division invited him to speak at our recent Congress (May 25, 2012); he discussed the ongoing evolution of his work in neuroimaging. Some of the highlights (reconstructed from tweet feed) were as follows:

1. What can we do with brain imaging, for differentiating the cognitive and emotional sides of pain perception? 
2. About 80-90% of pain research focuses on the nociceptive pathway.
3. However, S1[primary somatosensory cortex], S2 [secondary somatosensory cortex], ACC [anterior cingulate cortex], insular cortex, VP [ventroposterior nucleus] in thalamus, all activate with pain
4. There are activations in the cerebellum too (see Mick Sullivan for review of motor component of pain).
5. The question that interests Seminowicz: Can we image the dimensions of pain separately?

6. For the sensory-discriminative aspect, Bornhovd et al 2002 (1), imaging is largely intensity recording, S1 and insula. Downar et al 2003 (2)

7. Seminowicz's work is about imaging the cognitive evaluative component of pain. Manipulations include distraction and/or cognitive load
8. The DLPFC [dorsolateral prefrontal cortex] functions like an on-off switch.
9. The ACC signal changes over duration. 
10. In pain-cognition interactions, subjects were given a painful stimulation and a cognitive task at the same time, with four difficulty levels. The question was, what happens to brain activity?
11. When subjects are engaged in a task, intensity coding for pain is decreased.
12. How does pain affect cognition? Answer: it doesn't. If anything, it increases it a little. 
13. The more difficult the task, the more activated the networks become: pain activates them even more.
14. Pain itself acts as a cognitive load.
15. Subjects with chronic low back pain recruited more cortex to do the same kind of cognitive task.

16. The affective motivational domain can be manipulated through hypnosis/suggestion.
17. Intensity-coding region becomes more activated, with suggestion to that effect.
18. Empathic responses in brain activate the same regions (bilateral insular cortex and ACC) as does actual painful stimuli (Lamm et al 2011) (3)
19. The more DLPFC is activated the less other regions are active. 
20. Pain is personal, and so are pain-related activations: Coghill et al 2003 - Same temp was used, individual responses were counted - lots of variability. (4)
21. People who found it more painful had increased activity in insula, S1, etc., while thalamic activation showed no variability. 
22. In 2004 Seminowicz used electrical stim, plus the Stroop test to provide measurable cognitive load
23. Subjects ended up in two groups based on two behavioural responses - an "A" group and a "P" group.
24. The "A" group can easily distract themselves from pain by attending to cognitive tasks
25. Those in the "P" group, cannot. 
26. Two questions arise: 
Is pain cause or consequence of anatomical brain changes? 
Are these changes reversible?

27. In a rat model of sciatic nerve injury, imaging was done preinjury, chronic and treated:
decreased brain matter at 6 months
increase in anxiety behaviour correlated to decrease in brain vol.

28. In humans with chronic low back pain, when treated, they demonstrated decreased pain catastrophizing and thicker cortex.
29. So, the answers to the two questions are, 
"Seems so", and 
30. Pain didn't change but suffering was greatly reduced. 

Timothy Wideman (also on our PSD exec as chair elect), (seen here receiving the $4000 Ann Collins Whitmore Memorial Scholarship at Congress 2009) recently coauthored this paper with Seminowicz:  Effective Treatment of Chronic Low Back Pain in Humans Reverses Abnormal Brain Anatomy and Function (full access)

Seminowicz's several papers are listed on pubmed.

Here is a little nugget of his, from way back in 2006, open access - "Believe in your Placebo", published in The Journal of Neuroscience. Enjoy. :-) 

Some of the references mentioned during the lecture: 
1. Bornhövd KQuante MGlauche VBromm BWeiller CBüchel C.;  Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI studyBrain125 (6): 1326-1336. doi: 10.1093/brain/awf137   (Full Access)

2. Downar JMikulis DJDavis KDNeural correlates of the prolonged salience of painful stimulation 2003 Nov;20(3):1540-51.

3. Lamm CDecety JSinger T.; Meta-analytic evidence for common and distinct neural networks associated with directly experienced pain and empathy for pain 2011 Feb 1;54(3):2492-502. Epub 2010 Oct 12.

4. Coghill RCMcHaffie JGYen YF.;  Neural correlates of inter-individual differences in the subjective experience of pain 2003 Jul 8;100(14):8538-42. Epub 2003 Jun 24. (Full Access)