1. Functional imaging in chronic pain
Marwan N Baliki Ph.D.
Northwestern University
Department of Physiology
Apkarian pain and emotion Lab

2. Brain imaging in acute and chronic pain
Outline
Brain imaging in acute and chronic pain
1. Cortical mechanisms of acute and chronic pain
2. Impact of chronic pain on brain structure
Brain functional/structural changes associated with the transition of pain form acute to chronic state
Using functional imaging, we can identify suitable brain marker that can predict the onset of chronic pain after injury

3. Pain: general definition
Pain is one of the most important functions of the nervous system and provides information about the presence or threat of injury.
“an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”
Pain is a complex perception:
Sensory properties – quality, location, intensity
Affective properties - desire to avoid harm
Cognitive properties – appraisal of experience
Multiple distinct states :
Acute – transient (seconds to minutes)
Chronic – maladaptive (can last a lifetime)

4. Spinal cord pathways of pain

5. Brain activity for acute pain

6. Spontaneous pain rating in chronic back pain (CBP)

7. Brain activity for CBP Healthy CBP CBP (spontaneous pain)
(acute thermal pain)
Healthy
CBP
(spontaneous pain)

8. Different clinical pain conditions show distinct brain activity

9. Conclusions from functional studies
Brain activity for chronic pain ≠ acute pain
Chronic pain tends to activate limbic regions (amygdala, striatum and hippocampus)
Brain activity for clinical pain is specific for the clinical pain type

10. Chronic pain & brain structure

11. Global gray matter changes in chronic pain
CSF
White
Gray
2.5 cc/year of aging
1.5 cc/year of pain

12. Regional analyses show decreased gray matter in specific regions
Tension headache
(Schmidt-Wilcke et al 2005)
CRPS
(Geha et al 2008)
Fibromyalgia
(Kuchinad et al 2007)

13. Conclusions from structural studies
Chronic pain is associated with global and local changes in gray matter density
Morphological changes are specific for chronic pain type and reflect clinical properties of the condition
Evidence for reversal after cessation of pain

14. Chronic pain as emotional learning and memory
Pain chronification is not simply a consequence of the pain being experienced repeatedly over a sustained time period.
Cortico-striatal and cortrico-limbic brain circuitry may be directly involved in the development and maintenance of chronic pain.
Apkarian et al 2010

15. From acute to chronic pain (the clinical dilemma)
Sub-acute pain
A single intense episode of back pain lasting 4-16 weeks and no prior back pain for at least one year
Acute
pain
Chronic
Only a fraction (~ 5%) of subjects who experience an acute painful injury continue to develop chronic pain
No consistent behavioral, psychological or neurobiological factors can predict transition to chronic pain
To localize brain regions showing anatomical and functional changes

16. Why examine back pain ?
CBP is one of the 3 most common reasons for healthcare visits
Not more than 10-15% of such patients show associated physical changes
There are no scientifically validated treatments
It is associated with spontaneous pain (main reason for seeking medical care)

17. (>30% decrease in pain)
Study design
SBP
Persisting (SBPp)
(no change in pain)
Recovering (SBPr)
(>30% decrease in pain)
Consequences
Predictors

18. Clinical pain parameters

19. Longitudinal changes in gray matter density
SBPp and SBPr did not exhibit gray matter density differences at visit 1
All subjects
SBPp only

20. Differences in functional connectivity at visit 1
Right insula (visit 1)
Right NAc (visit 1)

21. mPFC – NAc connectivity predicts transition to chronic pain
Prediction
convert the visit 1 mPFC-NAc functional connectivity into quartiles (each category defined by z(r) change of 0.17)

22. Conclusions from longitudinal study
Persistent pain is associated with early mPFC-NAc coupling that is sustained over one year
mPFC – NAc functional connectivity may be a suitable marker for the development of chronic pain
Anatomical and functional changes were observed as early as 16 weeks after injury
Interventions should not only target the classical pain pathways, but also brain regions involved in motivation and emotion processing

23. Acknowledgments A Vania Apkarian Souraya Torbay Javeria Hashmi
Lejian Huang
Alex Baria
Bogdan Petre
Sara Berger
Souraya Torbay
Marivi Centeno
Ali Mansour
Kristina Hermmann
Amelia Mutso
Elle Parks