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Overview of Pain and Symptom Management

Narasimha Gundamraj MD

PAIN

• An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. (As defined by the International association for study of pain IASP)

Pain

• Pain is a protective mechanism for the body.• Pain prevents injuries

•

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Three Step Ladder

• 1. Non Opioids• 2. Mild Opioids• 3. Strong opioids• Continuous usage

Michigan Pain

• Effective April 1, 1999, the Pain and Symptom Management Advisory Committee was established under the Occupational Regulation sections of the Michigan Public Health Code, P.A. 421 of 1998.  The Pain and Symptom Management Advisory Committee Report was issued in November 2002. 

• The diagnosis and treatment of pain is integral to the practice of medicine.  In order to implement best practices for responsible opioid prescribing, clinicians must understand the relevant pharmacologic and clinical issues in the use of opioid analgesics and should obtain sufficient targeted continuing education and training on the safe prescribing of opioids and other analgesics as well as training in multimodal treatments. 

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Decade of Pain Control and Research 2001-2010

Pain types

Based on duration• Acute pain• Chronic pain

Acute Pain

• Due to noxious stimuli: Thermal, mechanical, chemical.

• Nociception: Detection (by receptors), transduction(localized processing of pain) , transmission of noxious stimuli ( signal transmission through nerves and spinal cord)

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Pain Types

• Nociceptive • Neuropathic

Types of Pain

• Somatic: Skin, subcutaneous tissues, mucous membranes.

‐Well localized‐Sharp, pricking, throbbing, burning‐Deep: muscles, tendones, bones• Visceral Pain: dull, diffuse, associated with sympathetic or parasympathetic activity. Parietal pain.

Nerve Fibers

• Size, degree of myelination, rapidity of conduction, distribution of fibers.

• A: Large myelinated. A delta‐Pain, A‐alpha‐motor and proprioception, Abeta/gamma‐skin touch and pressure.

• B: Medium sized. Post ganglionic sympathetic and visceral affarents.

• C: Unmyelinated.Pre ganglionic autonomic and pain.

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PCANausea & Constipation

•Chronic Pain

Chronic Pain

• Any pain that persists even after the removal of the noxious stimulus causing the pain

Chronic Pain

• 3 months

• International association for the study of pain IASP

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Chronic Pain

Chronic Pain Classification• Head, neck, truncal pain• Spinal and non spinal pain• Cancer Pain• Visceral pain

Chronic Pain

Chronic Pain Prevalence

• 10.1 to 55.2 %

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Pain pathwaysTreatment Modalities for

Chronic Pain

ModulateAscendingPathways

ModulateDescendingPathways

DecreaseSmall FiberInput

IncreaseLarge FiberInput

- antiinflammatory agents- opioids- nerve blocks or ablation

- Drugs: opiates, NSAIDs, TCAs,anticonvulsants

- Psychotherapy- Stress management- ? Acupuncture

- TENS- physical therapy- exercise

Controlled substances

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opioids

• Opioids are all compounds natural or synthetic that are functionally related to opium.

• Opiates are derived  or synthesized from Opium or Thebaine.

Endogenous opioids

• Endorphins• Enkephalins• Dynorphins

opioids

• Bind to opioid receptors• Types of opioid receptors: mu, kappa, delta, sigma

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opioids

• Mu receptor: Analgesia, respiratory depression, dependence, muscle rigidity.

• Kappa receptor: Sedation, Spinal analgesia• Delta: Analgesia, behavioral• Sigma: Dysphoria, hallucinations

• Function at Receptors: Full Opioid Agonists • Full agonist binding ... • activates the mu receptor, is highly reinforcing 

• is the most abused opioid typeincludes heroin, oxycodone, methadone, & 

others• Partial agonist: Buprenorphine 

• Morphine• Fentanyl, Sufentanil, Remifentanyl, Alfentanyl• Codeine• Oxycodone• Hydrocodone• Methadone• Buprenorphine

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Tramadol

• Weak mu agonist and weak norepinephrine‐seratonin reuptake inhibitor

• More use in neuropathic pain• Combined with acetaminophen

Plasma half life

Morphine 2 ‐ 3 hrs

Hydromorphone (Dilaudid) 2

Oxycodone 2 ‐4

Fentanyl 3.7

Meperedine (Demerol) 3‐4

Nalbuphine 5

Methadone 13‐50

Normeperedine 14‐21

Routes of administraton

• Oral: tablets, solutions.• Parenteral IV: Immediate post op, acute pain• Intramuscular, subcutaneous• Sublingual• Transdermal, fat depot• Transmucosal• Epidural, Intrathecal

Peak and duration of action

Morphine Immediate release oral tabletsPeakduration

1.1 hrs<6 hrs

Morhine controlled releasePeakduration

5.4 hrs8‐12 hrs

Morphine oral solutionPeakduration

0.5 hrs4‐6 hrs

Morphine rectalPeakduration

1 hr4‐6 hrs

Methadone oral tabletsPeakduration

2hrs6‐8 hrs

Oxycodone tablets and oral solutionPeakduration

3.1 hrs8‐12 hrs

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• Metabolized in Liver, Dependent on liver blood flow

• Morphine conjugates with glucoronic acid to form Morphine 3‐glucoronide and Morphine 6 –glucoronide

• Meperedine‐N‐demethylated to Normeperedine

• Eliminated in urine. 10% in Bile, 10% untransformed in urine.

Analgesia

• Sensory aspects in somatosensory cortex• Affective component  in Anterior cingulate cortex

• Actual does for analgesia is dependent on type and source of pain, patient factors.

Mood effects

• Anxiety relief• Euphoria• Dysphoria• Initial relief of depression and later exacerbation

• Reinforcing and reward  properties related to mesolimbic dopamine.

sedation

• Pre anesthesia• Reduce dose• Changing interval between doses• Avoid other CNS depressants• Tolerance to sedative effects

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Nausea and vomiting

• Stimulation of chemoreceptor trigger zone in medulla.

• IV route may cause more nausea than oral route.

Respiratory depression

• Brain stem repiratory centers• Dose related, route related• Caution in patients with obstructive sleep apnea, asthma and lung problems

• Opioid naïve patients, acute administration, associated with sedation

• Tolerance to respiratory depression

naloxone

• Opioid antagonist at mu receptor• Dose dependent• Medication dependent• Duration of action less than opioid

Other effects

• Pupillary constriction . (pinpoint pupils, repiratory depression, loss of consciousness)

• Antitussive• Hormonal effects, Opioid induced androgen deficiency (OPIAD), progestrerone suppression

• CNS excitability: Myoclonus, Siezures. Naloxone does not reverse, 

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Tolerance – Definition

• “Tolerance is a state of adaptation in which exposure to a drug induces changes that result in diminution of one or more of the drug’s effects over time”

TOLERANCE

• Normal physiological adaptation• Tolerance is less predictable than physical

dependence and develops more rapidly than analgesia

• Tolerance to analgesia, CNS depression and nausea, opioid induced constipation

Opioid induced hyperalgesia

• Upregulation of nociceptive systems• Rotation of opioids• Combining with non opioid

Selection of opioid

• Type of pain• Acute use• Chronic use• Adverse effects• Liver function, kidney function• Cost, availability• Clinical trial

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narcotics

• Are opioids narcotics?• Are all narcotics opioids?

Management of Chronic Pain

Assessment• Pain scores: may not be reliable• Subjective assessment: Vital signs, functionality

• Drug seeking behavior• Pain behaviors• Nurse shopping

Management of Chronic pain

• Oral bioavailability, gastrointestinal absorption, first pass hepatic clearence.

• Interpatient variability in opioid requirement• Age

Management of Pain

• Continue Patient’s baseline pain medications (long acting, fentanyl patch)

• Expect need for high doses compared to other acute pain patients in acute or hospital settings

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Management of Chronic Pain

Chronic pain and addiction treatment• Methadone• Buprenorphine

The Pain Cycle

GriefLonelinessDepressionInactivityFear/AnxietyInsomnia

Pain Suffering

Barriers to treatment of Pain

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Prescription drug abuse

• National survey on drug use and health(NSDUH)

• Substance abuse and mental health services administration(SAMHSA)

• 1/3rd of population aged 12 and over, first time drug users used prescription drugs (2009)

Prescription drug abuse

• In 2010 about 38,000 deaths per year, approximately 100 deaths per day due to drug ovedose.(NSDUH, SAMSHA)

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Michigan

Michigan• 1750 deaths due to drug overdose in 2009, compared to

962 from traffic deaths

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2011Prescription drug abuse prevention plan

• Education• Monitoring• Medication Disposal• Enforcement

Barriers to treatment of Pain

• Opioid dependence• Opioid tolerance• Opioid or substance abuse or addiction

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Addiction: DefinitionA primary, chronic, neurobiological disease, with

genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving

Consensus statement of the American society of addiction medicine, American academy of Pain medicine, American Pain Society

Addiction –A Neurobiological Disease

• The neurobiology of addiction encompasses more than the neurochemistry of reward

• There is altered impulse control, altered judgment, and the dysfunctional pursuit of rewards

• Susceptible individuals may have an alteration of the limbic or related system that causes sensitization to the reinforcing effects of drugs

• Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry

Addiction –Behavioral Manifestations

• A Inability to consistently Abstain• B Impairment in Behavioral control• C Craving; or increased “hunger” for

drugsor rewarding experiences

• D Diminished recognition of significantproblems with one’s behaviors andinterpersonal relationships, and

• E A dysfunctional Emotional response

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• Physical dependence• Tolerance• Pseudoaddiction

Physical Dependence – Definition“Physical dependence is a state of

adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist”

• Normal predictable, physiological response

• Characterized by drug class specific physical withdrawal syndrome

• Can develop to opioids within a week• Taper the dose to prevent withdrawal• Opioid withdrawal symptoms can persist

for weeks to months in some persons

Tolerance – Definition

• “Tolerance is a state of adaptation in which exposure to a drug induces changes that result in diminution of one or more of the drug’s effects over time”

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• Normal physiological adaptation• Tolerance is less predictable than physical

dependence and develops more rapidly than analgesia

Pseudoaddiction

• Results from the undertreatment of pain• Manifested by behaviors similar to

addiction– Clock watching– Focus on obtaining drug– Aberrant behaviors

• Behaviors resolve when the pain is effectively managed

Substance abuse and Pain management

• Pain management in individuals with substance abuse issues

• Opioid pain management leading to misuse and substance abuse

Opioid Agreements

• Written documents signed by both clinician and patient

• Spell out expected behaviors and consequences of these behaviors

• Purpose is to promote safe and effective use of controlled substances

• Provide “informed consent” on risks and benefits of long-term opioid therapy

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Assessment: Interview Tips• Be nonjudgmental• Explain importance of information• Assume use: how often do you use?• Estimate high quantities: do you drink

about a quart (or case) a day?• ? Feelings of impending withdrawal• Be aware of stages of change• Use established assessment tools

Analgesia

• Goal is to provide pain relief– Increased comfort should improve the

patient’s quality of life• Perform and document routine pain

assessments:– Average pain during the past week (0-10)– Worst pain during the past week (0-10)– % of pain relief in the past week– Inpatient assessment of patient’s pain behaviors

Activities of Daily Living

• Goal is to increase activities of daily living– Pain relief should improve function

• Conduct a routine functional assessment:– Physical functioning– Mood– Sleep– Relationships – Family and Social Networks– Overall

Adverse Events

• Goal is to minimize adverse events– Adverse events could affect adherence

• Conduct a routine assessment of side effects:– GI: Constipation, nausea, vomiting– CNS: Mental clouding, drowsiness, fatigue– Other: Itching

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Assessment tools

• Current opioid misuse measure (COMM)• Screener and opioid assessment for

patients with pain-revised (SOAPP-R)• Substance abuse subtle screening

inventory (SASSI)(SASSI-A2)

Maintainence

• Routine follow up• Pill counts• Random Urine drug screen• MAPS

Guidelines for prescriptions

• State guidelines• Federal guidelines: FSMB, CDC

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Michigan

• Evaluation of patient• Treatment plan• Informed consent and agreement for treatment: one physician, one pharmacy, urine drug screens, frequency of prescriptions, terms for discontinuation

• Periodic review• Consultation• Medical records• Compliance with controlled substances laws

Michigan automated prescription system MAPS

• Database of Michigan department of community health

• Physicians, Dentists, Nurse practitioners, Physician assistants, Pharmacists, Podiatrists, Veterinarians

• Drug, dosage, amount, date prescribed, date dispensed, prescribing physician name, pharmacy name

CDC GuidelinesMarch 15th 2016.

• Guidelines not rules• Primary care physicians not oncologists• Consider non opioid options: NSAIDs, physical therapy, behavioral treatments

• Not more than 7 day treatment for acute pain

CDC GuidelinesChronic therapy

• Follow up 1‐4 after initiation, then every 3 months

• Urine drug screens atleast once a year• MAPS review atleast every 3 months• Document:  Benefits outweigh risks, non pharmacologic/non opioid therapy used, Improvement of function

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CDC Guidelinesdosage recommendations

• Less than 50 mg morphine equivalents per day• 50  to 90 mg (MME) only when beneficial• >90 mg rarely used• Avoid benzodiazepines

Prescription opioids Pharmacist’s perspective

• E prescriptions• Michigan Chief Medical Executive  ( Dr.Wells) Standing order for Naloxone

• Out of town patients• Number of pills• Cash pay• Circle of friends from same physician

Pain Management

• Cause of pain?• Is the pain adequately controlled?

• Risk of developing addiction with acute pain management is small

• Risk of developing addiction or aberrant behaviors in chronic pain patients is about 3%.

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High risk predictors

• History of alcohol or illicit drug use• Family history• History of convictions for drunk driving or

drug use, cigarette smoking.• Aberrant behaviors in the course of

therapy.• Early refills, preoccupation with opioids,

doctor shopping

Aberrant Drug-Related Behaviors

• Goal is to detect aberrant drug-related behaviors early on to prevent abuse, diversion and protect the practice of pain management

• Consider– Cultural norms– Less predictive behaviors– More predictive behaviors

Aberrant Behaviors

• Borrowing drugs from family and friends• Hoarding drugs

– With improvement of symptoms– With resolution of the problem

Less Predictive Aberrant Behaviors

• Drug hoarding when symptoms are improved• Acquiring drugs from multiple medical sources• Aggressive demands for a higher dose• Unapproved use of a drug to treat a symptom,

e.g., use of an opioid to treat anxiety• Unsanctioned dose escalation (1-2x)• Reporting psychic effects• Requesting specific drugs

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More Predictive Aberrant Behaviors• Selling prescription drugs• Forgery of prescriptions• Concurrent illicit drug use• Multiple prescription/medication losses• Ongoing unsanctioned dose escalations• Stealing and borrowing drugs• Obtaining prescription drugs from nonmedical source• Non-sanctioned route of administration• Repeated resistance to change – inflexibility

Causes of Aberrant Behaviors• Addiction or pseudoaddiction?• Pseudotolerance• Psychiatric disease

– Personality disorder– Depression, anxiety

• Organic encephalopathy • Situational stressors• Chemical coping• Criminal intent

Dispensing Issues

• One provider• One pharmacy• Limit the amount of medication given at

any one time– Weekly vs monthly

Urine drug testing

• GCMS, LCMS• Tests positive for medications prescribed• Tests negative for drugs not prescribed or other illicit substances of abuse

• Marijuana

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Urine Drug testing

• Metabolites of prescribed medications• Medications not prescribed• Illicit drugs of abuse

When do you do UDS?

• Anytime• Start of prescribing either short term or long term opioids

Urine drug tests Urine drug tests

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Urine Drug tests

Discontinuation Vs Weaning

• Suspicion of diversion• Negative urine tests• Positive urine tests along with illegal substances

• Withdrawal

2011Prescription drug abuse prevention plan

• Education• Monitoring• Medication Disposal• Enforcement

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How to achieve goals

• Communication• Vigilence

Barriers to Pain Relief Related to Addiction

• Healthcare professionals may underprescribe– Lack of knowledge about addiction, tolerance, and

physical dependence– Fear of scrutiny by regulatory agencies

• Patients and Families– Patients may be reluctant to take opioids because of

fears and confusion about addiction– Families may withhold analgesics from patients

• Healthcare Systems

A Multidisciplinary Team

Patient

Physician

Addiction-ologist

Sponsor

CounselorSocialWorker

Psychologist

Nurse

Nursing Role• Collaborate with other health care team

members• Assess for the presence of pain/addiction and

related symptoms such as anxiety and depression

• Assess, document, and report aberrant behaviors

• Advocate for effective pain management • Provide ongoing communication with the family

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Challenges to Nurses• Behaviors that seem “manipulative”

– Favoring one nurse over another– Complimenting nurses who respond to

requests– Exhibiting anger when needs are unmet

• Requesting IV medications be given “fast”• CONSISTENCY is the key to working with

this population ..BE CAREFUL about making exceptions

Assess and Document Outcomes of Opioid Therapy

• Analgesia– Pain relief

• Activities of Daily Living– Physical, social and emotional function

• Adverse Events– Side effects or other adverse events

• Aberrant Drug-Related Behaviors– Behaviors suggestive of addiction

Goals of therapy

• Effective pain relief• Treat symptoms• Prevent withdrawal• Prevent risk or relapse to addiction• Treatment of comorbid psychiatric issues• Prevent barriers to treatment

Goals of therapy

• Patient safety• Pain control

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