Negative Affect And Chronic Pain

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Negative Affectand Chronic PainAjay D. Wasan, MD, MScProfessor and Vice Chair for PainMedicineDepartments of Anesthesiology &Perioperative Medicine; and Psychiatry

Agenda Concept of Negative Affect Epidemiology of NA and Pain Brain physiology and pain Clinical studies of NA andpain

What is Negative Affect?AKA Negative Valence Disorders20% of CLBP patients have a co-morbiddepression or anxiety disorder--Edwards RR, Wasan AD, et. al., J Pain, 2016Affect Thoughtsemotions, andbehaviorPainCatastrophizing Negativethoughts aboutpainNA3

Common Psychiatric Symptoms in Patients with Paincan be Described as Negative Affective DisordersCorrelations of .60-.70 between these categories Negative Affect, AKA Negative ValenceIn a broad rangeof chronic painconditions theserelationshipshold trueRyan and McGuire,Brit J Health Psych,2016CorePsychopathologyGeneralized AnxietyMajor DepressionCharacter pathology(ex. neuroticism, orpersonality disorder)DSM relatedcategoriesPain-related Rx OpioidAddiction andother SUDsPoor Self-efficacyPassive CopingPain-related AngerOutcomesPainPain sensitivityInflammationDisabilityPoor TXresponse Quality of Life Mental Health Pain-research based“constructs”Redrawn and adapted from Wasan AD and Alpay M, “Pain and the PsychiatricComorbidities of Pain,” in Comprehensive Clin. Psychiatry, 2nd Ed., 2016, Elsevier Pub.4

Scope of the Psychopathology 15-20% of those in the general population who have chronic painhave significant psychopathology. 30-40% of those with chronic pain in Primary care havepsychopathology 50-80% of patients with chronic pain seen in pain clinics have amajor psychiatric disorder, by DSM criteria. 30-50% of the comorbidity is major depression, followed by anxietydisorders, adjustment disorders, personality vulnerabilities(Neuroticism), somatic symptom d/o (primary), and substanceabuse.Dersh J, JOEM, May 2002

Affective Pain Processing Emotional components of pain—sense of unpleasantness, sufferingassociated with pain, sadness or anxiety that may be evoked by pain. Meanings of pain—is pain a nasty sensation that still permits a goodquality of life vs. a state of torment and despair, where one’s life is ruined? Attention to pain—can you notice it less, or does it overwhelm yourconsciousness? Both the emotional and cognitive components of the pain experience formthe affective response to CHRONIC pain AKA Secondary Pain Affect.Price, Science, 2000

Who are the patients with psychiatricproblems? In general, they tend to be the ones with pain complaints anddisability out of proportion to their anatomic pathology. Little variability of pain day or night Poor response to medications or procedures

Patients with psychiatric problems usually have a combination ofpsychiatric and physical pathology that amplifies the anatomicbasis of their pain. Psychiatric problems are the most significant comorbidities ofchronic pain and are the greatest predictor of poor pain anddisability outcome, regardless of pain diagnosis! Most psychiatric problems are treatable, or at least can getsignificantly better.Clark 2002, Psych Clinics N. America 25:March 2002

Most patients developed psychopathology after the pain began. You get optimal relief of pain and improvement inpsychopathology with treatment of both simultaneously. Psychiatric problems can be contraindications to procedures—spinal cord stim or IT pump. Operational definition of HIGH negative affect in our studies: High levels of BOTH depression and anxiety symptoms Captures the majority of the variance between the different NAconstructs (depression, anxiety, catastrophizing, etc) Those with high depression more likely to have high anxiety orCATLin, Jama, 2003

Positive Affect45Negative AffectPositive Affect40Score (0-50)35302520151050Pre-Surgery6 Weeks PostTime3 Months Post141 patients treated by spine surgeryfor lumbar or cervical degeneration.Affect was measured with thePANAS. Negative affect decreasedpost-surgery while positive affectremained constant. Linear regressionanalyses found that 6-week positiveaffect predicted functional status at 3months following surgery.10

Martucci KT,and Mackey SC,“Neuroimagingof Pain,”Anesthesiology,2018 (128)p.1241-5411

The Brain as a ‘Dynamic Connectome’ Underdeveloped area of how chronicpain is processed in the brain and howthat processing may change withsuccessful treatment. Neuroimaging studies suggest thatthere are a host of structural andfunctional abnormalities in the brainthat perpetuate and amplify painprocessing and pain perception in thebrain. Davis KD, J Neuroimmune Pharmacol,201312

Correlated to painanticipatory activityR LPFC A R LPFC right lateral prefrontal cortex; B Activity in PFC correlated tocatastrophizing score; C PFC activity correlated to cuff pressure; D PFCactivity mediates the effect of catastrophizing on cuff pressurePain sensitivityandcatastrophizing 31 patients with FM Cuff pain stimuliduring fMRIscanning LPFC activitymediated therelationship btw CATand cuff pressure Loggia ML, et, al., JPain, 201513

Depressed Mood and PainB**6N 20 healthy subjects.5VAS visual analog scale.Berna C, et. al. Biol Psychiatry. 2010;67:1083-1090.In Vivo Catastrophizing(VAS 0-10)*P 0.05. **P 0.01.Pain Unpleasantness(VAS 0-10)* P 0.05. **P 0.01.C3***Depressed moodNeutral mood21Magnification Rumination Helplessness

15Practical PainManagementCentralized Pain TaskForce, PPM, April,2015

Brain glial activityand pain 10 CLBP patients vs.matched controls TSPO ligand has aspecificity for glial cells Loggia ML, et. al, Brain,201516

In CLBP patients (n 25) Glial cell activation vs.Depression scores Processing of pain andaffect overlap in the brain inareas such as the ACC,Insula, and PFCMany mechanisms by whichlimbic areas can amplify theperception of pain andworsen functionKnown as the “dynamicconnectome” that describesSalience Networks in thebrain related to pain Functional connectivity(interactions) between ACC,Insula, and PFC explained asignificant portion of BDI scoresAlbrecht DS, Wasan AD, &Loggia ML, et.al, MolecularPsychiatry, 2019, “TheNeuroinflammatory Componentof Negative Affect in Patientswith Chronic Pain”17

59.360IV MSO4 Resultsa47.6b, 27.2b17.130205.314.5d, edLowModa-e significant pairwise comparisonsa .006 b .02616.3e“The Impact of PsychiatricComorbidity on OpioidAnalgesia in Discogenic LowBack Pain”100cc .01 d .05 e .01HighWasan AD, Davar G, JamisonRN, Pain, 200518

Wasan AD, et. al., “Psychiatric Comorbidity Is Associated Prospectively withDiminished Opioid Analgesia and Increased Opioid Misuse in Patients withChronic Low Back Pain,” Anesthesiology, 2015 N 55 patients with CLBP, Hi and Lonegative affect (depression anxietysymptoms) Prescribed opioids over 5 months, withthe prescriber blinded to group Tracked pain daily MISUSE 8% rate of opioid misuse in the Lowgroup 38% misuse rate in the High group19

Facet Syndrome and TherapeuticMedial Branch Blocks20 Axial low back or neck pain—with concordant PE MRI or CT findings of facet arthropathy Positive bone scan predicts positive response with MBB Effectiveness Improvement in pain and function

Low**(n 37)%Percent ofPatients withat least 30%improvementAD Wasan, et.al, BMC MSKDisorders, 20094545%40Responders21**between groupcontrast, p .004353025Mod**(n 20)2010%15High**(n 29)10%1050LowModHighPsychopathology GroupSimilar findingsin patientsundergoingspine surgeryor epiduralsteroidinjections

Psychiatric History and Psychological Adjustment as RiskFactors for Aberrant Drug-Related Behavior amongPatients with Chronic Pain Multi-center pain clinic study of 229 patients on opioidtherapy for non-cancer pain Multiple measures of opioid misuse potential at start ofstudy Several questions on psych hx or negative affect symptoms High and Low groups of comorbid psychopathology Followed 6 months Completed surveys of opioid use, urine tox screens, andphysician ratings of adherenceWasan AD, and Jamison RN, et al., Clin J Pain, 2007: 23 (4), 307-1522

Table 3. Differences between high and low psychiatric co-morbidity patients on theSOAPP, COMM, POTQ, urine toxicology results, and Aberrant Drug-RelatedBehavior IndexVariableHigh PsychLow PsychpSOAPP total score†10.0 ( 6.1)6.4 ( 5.0)t 4.63***COMM total score‡12.6 ( 7.7)7.1 ( 6.1)t 5.84***POTQ total score (% positive) 23.720.0nsUrine toxicology (% positive)34.418.4X2 7.26**Aberrant Drug Index (% yes)¶52.322.9X2 19.34***p 0.01***p 0.001ns nonsignificantscores 7 were positive ‡ COMM scores 8 were positive POTQ score 2 is pos¶ Aberrant Drug Behavior Index ( scores on SOAPP and COMM, or scores on the POTQand urine score)†SOAPP23

Does the concept of craving for opioids link NA and opioidmisuse? Clinical Journal of Pain, 200924

What does craving for prescription opioids mean?N 60, divided into 3 groups, 2 high risk, 1 low risk, datacollected daily for 2 weeks over the 6 month studyWasan AD, et. al,J Pain , 201025

Components of craving for prescription opioidsUrgeMoodCorrelations .66-.82Preoccupationwithnext dose.07-.10Pain noworAvg painCraving Levels of craving are a key predictor of relapse insmoking, ETOH, or cocaine use Postulated elements of craving—what are theserelationships? Would craving predict misuse in an RCT?26

Consequences of High Negative Affect in Chronic PainRECAP Significantly greater pain and disability Treatment resistance to opioid medications,nerve blocks, & spine surgery Greater rate of opioid misuse N 82 patients with chronic pain prescribedopioids and enrolled in an RCT to decreaseopioid misuse through individual and groupmotivational interviewing and adherenceeducationTracked opioid misuse and craving over 6month periodMartel MO, Wasan AD, et. , al., “The association betweennegative affect and prescription opioid misuse in patientswith chronic pain: The mediating role of opioid craving,”Drug and Alcohol Dependence, 201327

Mental Health DisordersAssociated with MoreOpioid Prescribing Examined 950,000 insurancerecords from commercial andMedicaid claims DX of Depression or anxiety2-3 times as likely to beprescribed an opioid

Evaluated 1334 chronic pain patients prescribedopioids chronically Self report of misuse, such as self-medicatingnon-pain, increasing doses, or obtaining opioidsfrom others Patients with major depression 2X as likely tomisuse opioids Most commonly by self-increasing their dose N 1193, pain clinic sample

NA and Rx Opioid ODResults. The strongest associations with seriousOIRD in CIP were diagnosed substance use disorder(odds ratio [OR] 10.20, 95% confidence interval[CI] 9.06-11.40) and depression (OR 3.12, 95%CI 2.84-3.42). Other strong associated factorsincluded other mental health disorders Analyzed Insurance claimsdata (VA and commercial) in18 million patients

Retrospective cohort study of 4155patients presented to a Univ. ofPittsburgh ED with opioid ODRates of repeated OD within 1 yearand predictive factorsDiagnosisMental Health diagnosesDepression disorderAnxiety disorderBipolar disorderStress disorderSchizophreniaAny mental health disorderNo mental health disorderDrug and alcohol diagnosesSubstance use disorderAlcohol use disorderAdjusted Hazard Ratio(95 % CI)1.38 (1.02, 1.73)1.41 (1.13, 1.77)1.32 (0.96, 1.82)1.38 (0.84, 2.27)1.14 (0.57, 2.29)1.32 (1.08, 1.61)0.76 (0.62, 0.92)1.30 (1.09, 1.56)1.52 (1.02, 2.26)

Thank You!Acknowledgements Brigham and Women’sHospital/Harvard Medical School–––– University of Pittsburgh Andrea Gillman Jim Ibinson Jeong JongRobert EdwardsSrdj NedeljkovicRobert JamisonJeff Katz MGH Martinos Center/HMS––––Marco LoggiaVitaly NapadowRandy GollubJian Kong32

psychiatric and physical pathology that amplifies the anatomic basis of their pain. Psychiatric problems are the most significant comorbidities of chronic pain and are the reatestg predictor of poor pain and disability outcome, regardless of pain diagnosis! ost psychiatric problems are treatable, or at least can get M significantly better.

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