Brain PET Scans in Patients with Brain PET Scans in Patients with Minimal Pain Minimal Pain

Departments of Anesthesiology, Radiology, and Neurology Departments of Anesthesiology, Radiology, and Neurology Rush University Medical CenterRush University Medical Center

Rush Medical College Rush Medical College Chicago, IL Chicago, IL

Asokumar Buvanendran, MD, Amjad Ali, MD, Travis R. Stoub, PhD, Asokumar Buvanendran, MD, Amjad Ali, MD, Travis R. Stoub, PhD, Jeffrey S. Kroin, Ph.D., Kenneth J. Tuman, M.D. Jeffrey S. Kroin, Ph.D., Kenneth J. Tuman, M.D.

IntroductionIntroduction• Positron emission tomography (PET) is an Positron emission tomography (PET) is an

imaging technique that can quantify increases in imaging technique that can quantify increases in nerve cell activity in selective regions of the brain. nerve cell activity in selective regions of the brain.

• Earlier studies have examined the pattern of Earlier studies have examined the pattern of increased brain activity that follows increased brain activity that follows experimentally-induced acute pain.experimentally-induced acute pain.1,2,31,2,3

11 BrainBrain 1998;121:931. 1998;121:931.

22 J NeurophysiolJ Neurophysiol 1999; 82:1934. 1999; 82:1934.

33 Anesth AnalgAnesth Analg 2007; 105:1784. 2007; 105:1784.

Can Pain Be Measured?Can Pain Be Measured?

Is Seeing Believing?Is Seeing Believing?

Increased Activity in the Brain with PainIncreased Activity in the Brain with Pain

• 6 different areas are being studied:6 different areas are being studied:• Anterior Cingulate Cortex (ACC)Anterior Cingulate Cortex (ACC)

Primary Somatosenory Cortex (S1)Primary Somatosenory Cortex (S1) Secondary Somatosensory Cortex (S2)Secondary Somatosensory Cortex (S2) Insular Cortex (IC)Insular Cortex (IC) Pre-frontal Cortex (PF)Pre-frontal Cortex (PF) ThalamusThalamus

Moderate Postoperative Pain and Brain Moderate Postoperative Pain and Brain Activation After TKAActivation After TKA

• Baseline MRI of the brain and PET scanBaseline MRI of the brain and PET scan• Epidural Anesthesia and Analgesia for Epidural Anesthesia and Analgesia for

postoperative painpostoperative pain

• Stopped epidural:Stopped epidural: Moderate pain Moderate pain →→ PET PET

• Epidural infusing: Epidural infusing: No PainNo Pain → → PETPET

Postoperative Postoperative Moderate Pain after Moderate Pain after

Left TKALeft TKA

ThalamusThalamus

Contralateral Contralateral Somatosensory Somatosensory

CortexCortex

Right side Right side PrecuneusPrecuneus

Current StudyCurrent Study• However, baseline PET activity (pre-stimulation However, baseline PET activity (pre-stimulation

or pre-surgery) in the brain has not been or pre-surgery) in the brain has not been examined in detail.examined in detail.

• Knowledge of baseline activity in patients with no Knowledge of baseline activity in patients with no pain or mild pain prior to surgical or anesthetic pain or mild pain prior to surgical or anesthetic intervention is important for future research intervention is important for future research involving PET assessment of modulation of involving PET assessment of modulation of postoperative pain. postoperative pain.

• In this study we examine PET brain activation at In this study we examine PET brain activation at rest in six patients with minimal pain. rest in six patients with minimal pain.

MethodsMethods

In a quiet room with low ambient light, fasted patients In a quiet room with low ambient light, fasted patients were injected intravenously with the PET radionuclide were injected intravenously with the PET radionuclide 18F-fluoro-2-deoxyglucose.18F-fluoro-2-deoxyglucose.

After waiting at least 30 min, a brain PET scan was After waiting at least 30 min, a brain PET scan was performed. performed.

Prior to each PET scan, pain scores were measured Prior to each PET scan, pain scores were measured using the verbal rating scale, with 0=no pain, using the verbal rating scale, with 0=no pain, 10=worst imaginable pain. 10=worst imaginable pain.

AnalysisAnalysis

For the patients, digital files of PET scans were co-For the patients, digital files of PET scans were co-localized with a standard stereotaxic MRI. localized with a standard stereotaxic MRI.

To compare PET scans among different patients, a To compare PET scans among different patients, a linear normalization was applied by dividing regional linear normalization was applied by dividing regional activity by whole brain activity for each scan.activity by whole brain activity for each scan.11

A relevant increase in glucose metabolism was A relevant increase in glucose metabolism was assumed if more than 50 adjacent voxels showed a Z assumed if more than 50 adjacent voxels showed a Z score > 2.score > 2.2

11 Eur NeuropsychopharmEur Neuropsychopharm 2002;12:527-44. 2002;12:527-44. 2 2 JNNPJNNP 2003; 74:922 2003; 74:922

The mean baseline pain score in the six patients was The mean baseline pain score in the six patients was 1.17 (range 0-2). 1.17 (range 0-2).

ResultsResults

PET activation in these subjects was primarily in the occipital lobe, and PET activation in these subjects was primarily in the occipital lobe, and putamen bilaterallyputamen bilaterally

PutamenPutamen

Occipital lobeOccipital lobe

There was There was nono significant activation in pain- significant activation in pain-related regionsrelated regions

Somatosensory cortex (SI or SII)Somatosensory cortex (SI or SII)

SI

SII

Anterior cingulate gyrus (ACC)Anterior cingulate gyrus (ACC)

ACCACC

There was There was nono significant activation in pain-related significant activation in pain-related regionsregions

Insula Insula

Also, no activation in thalamusAlso, no activation in thalamus

There was There was nono significant activation in pain-related regions significant activation in pain-related regions

DiscussionDiscussion

• To fully comprehend acute, chronic, and postoperative pain To fully comprehend acute, chronic, and postoperative pain PET studies, baseline brain activation must be characterized.PET studies, baseline brain activation must be characterized.

• In patients reporting minimal pain, we have established that In patients reporting minimal pain, we have established that there was no brain activation in pain-related regions.there was no brain activation in pain-related regions.

• This suggests that changes in brain activation after This suggests that changes in brain activation after intervention (e.g. joint replacement surgery) will not be intervention (e.g. joint replacement surgery) will not be obscured by the patient’s baseline brain activity as long as the obscured by the patient’s baseline brain activity as long as the baseline pain score is 2 or less.baseline pain score is 2 or less.

Some activity in superior temporal gyrus and frontal Some activity in superior temporal gyrus and frontal cortex: Not Pain Activated sitecortex: Not Pain Activated site

Sup Temporal GyrusSup Temporal Gyrus Frontal cortexFrontal cortex