"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?


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


COGNITIVE-EVALUATIVE ASPECT
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.


AFFECTIVE-MOTIVATIONAL ASPECT
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:
Observations:

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 

"Maybe". 

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 K, Quante M, Glauche V, Bromm B, Weiller C, Büchel C.;  Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study. Brain (2002) 125 (6): 1326-1336. doi: 10.1093/brain/awf137   (Full Access)


2. Downar J, Mikulis DJ, Davis KD. Neural correlates of the prolonged salience of painful stimulation. Neuroimage. 2003 Nov;20(3):1540-51.


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


4. Coghill RC, McHaffie JG, Yen YF.;  Neural correlates of inter-individual differences in the subjective experience of pain. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8538-42. Epub 2003 Jun 24. (Full Access)