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

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

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)

Spinal cord pathways of pain

Brain activity for acute pain

Spontaneous pain rating in chronic back pain (CBP)

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

Different clinical pain conditions show distinct brain activity

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

Chronic pain & brain structure

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

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)

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

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

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

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)

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

Clinical pain parameters

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

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 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