Functional imaging in chronic pain

Marwan N Baliki Ph.D.

Northwestern University

Department of Physiology

Apkarian pain and emotion Lab

Brain functional/structural changes associated with the transition of pain form acute to chronic state

Outline

Brain imaging in acute and chronic pain

1. Cortical mechanisms of acute and chronic pain 2. Impact of chronic pain on brain structure

Using functional imaging, we can identify suitable brain marker that can predict the onset of chronic pain after injury

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: general definition

Pain is a complex perception:

1. Sensory properties – quality, location, intensity2. Affective properties - desire to avoid harm 3. Cognitive properties – appraisal of experience

Multiple distinct states :

1. Acute – transient (seconds to minutes)2. Chronic – maladaptive (can last a lifetime)

Spinal cord pathways of pain

Brain activity for acute pain

Spontaneous pain rating in chronic back pain (CBP)

CBP (spontaneous pain)

CBP (acute thermal pain)

Healthy(acute thermal pain)

Brain activity for CBP

Different clinical pain conditions show distinct brain activity

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

Conclusions from functional studies

Chronic pain & brain structure

1.5 cc/year of pain2.5 cc/year of aging

CSF White Gray

Global gray matter changes in chronic pain

Tension headache(Schmidt-Wilcke et al 2005)

CRPS(Geha et al 2008)

Fibromyalgia (Kuchinad et al 2007)

Regional analyses show decreased gray matter in specific regions

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

Conclusions from structural studies

Chronic pain as emotional learning and memory

Apkarian et al 2010

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.

From acute to chronic pain (the clinical dilemma)

Acute pain

Chronic pain

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

Sub-acute pain

A single intense episode of back pain lasting 4-16 weeks and no prior back pain for at least one year

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)

Why examine back pain ?

Study design

SBP Persisting (SBPp)(no change in pain)

Recovering (SBPr)(>30% decrease in pain)

Predictors

Consequences

Clinical pain parameters

Longitudinal changes in gray matter density

All subjects SBPp only

SBPp and SBPr did not exhibit gray matter density differences at visit 1

Differences in functional connectivity at visit 1

Right insula (visit 1) Right NAc (visit 1)

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)

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

Acknowledgments

A Vania ApkarianJaveria HashmiLejian Huang

Alex BariaBogdan PetreSara Berger

Souraya TorbayMarivi Centeno

Ali MansourKristina Hermmann

Amelia MutsoElle Parks