1. On Pain: Taking the pain out of pain management
Suzana Makowski, MD MMM FACP
Palliative Care
UMassMemorial/UMassMedicalSchool

2. Overview
• Pain assessment review
• Opioid pharmacology: what I wish I had known...
• Pain syndromes

3. • Intensity
Assessing pain: • Location
• Quality: Nociceptive/Neuropathic
The easiest pain to tolerate is someone else’s • Timeline
• Alleviating/Exacerbating factors

4. Pain Intensity
• Visual analogue scale: No pain-------------------------Worst pain
• Numeric scale: 0 - 1 - 2 - 3 - 4 - 5 - 6 - 7 - 8 - 9 - 10
• Categorial scale: mild (1-3) - moderate (4-6) - severe (7-10)
• FACES scale:
• PAID-AD scale:

5. PAINAD Scale: for non-verbal patients with
dementia

6. Pain Assessment: Timeline
Intensity
Time

7. Challenges to pain assessment
• Acute vs. chronic pain • Dependence
• Concerns about addiction and • Tolerance
abuse/misuse
• Addiction
• What else?
• Pseudoaddiction

8. Barriers to Pain Management
Physician-Related
• Limited knowledge of pain pathophysiology and assessment skills
• Biases against opioid therapy and overestimation of risks
• Fear of regulatory scrutiny/action
Patient-Related
• Exaggerated fear of addiction, tolerance, side effects
• Reluctance to report pain: stoicism, desire to “please” physician
• Concerns about “meaning” of pain (associate increased pain with worsening disease)
System-Related
• Low priority given to pain and symptom control
• Limits on number of Rxs filled per month & number of refills allowed
• Reimbursement policies
(American Pain Society, 2001; Glajchen, 2001; Lister, 1996; Portenoy RK, 1996; Weinstein et al, 2000)

9. Racial & Ethnic Barriers
• Language or cultural differences make pain assessment more difficult
• Physiciansʼ perceptions and misconceptions:
✴minority-group patients have fewer financial resources to pay for
prescriptions
✴higher drug-abuse potential among minority groups
• Patients’ lack of assertiveness in seeking treatment
• Lack of treatment expertise at many sites at which minority-group patients
are treated
• Relative unavailability of opioids in some communities
(Bonham, 2001; Glajchen, 2001)

10. Untreated pain can lead to worsening chronic pain
• In chronic pain, the nervous system remodels continuously in
response to repeated pain signals
• nerves become hypersensitive to pain
• nerves become resistant to antinociceptive system
• If untreated, pain signals will continue even after injury resolves
• Chronic pain signals become embedded in the central nervous system

11. Chronic Pain Syndromes: Cancer, Chronic Low Back Pain, Osteoarthritis,
Fibromyalgia

12. Cancer pain
Highly prevalent:
• 30-50% in active treatment
• 75-90% in advanced illness
Principles of Assessment
Pain History
• chronicity
• intensity and severity
• pathophysiology and mechanism
• tumor type and stage of disease
• pattern of pain and syndrome
Physical and Neurologic Examination
Radiographic Findings

13. Cancer Pain Treatment considerations
Identify the cause of the pain
• Primary treatment if indicated
• WHO ladder combined with etiology-specific therapies for syndromes
✴pharmacologic and nonpharmacologic interventions
✴long-acting + short-acting opioids
✴adjuvant medications for neuropathic pain
✴NSAIDs and steroids can be helpful when there is an inflammatory
component to pain

14. WHO guidelines
• Step 3: Opioid for moderate
to severe pain
+/- adjunctive treatment
+/- non-opioid
Pain Persists
• Step 2: Opioids for mild to
moderate pain
+/- adjunctive treatment
+/- non-opioid
Pain Persists
• Step 1: Non-opioid
+/- adjunctive treatment
(Adapted from Portenoy et al, 1997)

15. Chronic Low Back Pain
• 60-85% lifetime prevalence
Clinical Characteristics
• Preoccupation with pain
• Consistently disabled from
pain
• Depression and anxiety are
common
• High incidence of psychiatric
diagnoses
• Drug misuse is common, but
addiction relatively rare

16. Low-Back Pain Treatment Considerations
• Analgesic Medications
• Adjuvant Analgesics
• Physical Therapy Approaches
• Neural Stimulation
• Psychologic Management
• Multidisciplinary Pain Centers

17. Osteoarthritis
• Affects over 80% of people over 55
• 23% have limitation of activity
Diagnosis
• History: age, functionality, degree of pain, stiffness, time of occurrence
(e.g., morning, at rest, during activity)
• Physical examination: range of motion, tenderness, bony enlargement
of joint
• Laboratory findings: radiograph, CBC, synovial fluid analysis

18. Osteoarthritis Treatment Considerations
• After comprehensive assessment of function and pain
Mild to moderate pain Acetaminophen
Moderate to severe pain COX-2 and NSAIDs
Severe arthritic pain (unresponsive
to non-opioid, or for elderly at risk Opioids
for renal insufficiency)
Drug therapy ineffective or
Surgery
debilitating pain/function

19. Pain treatment
• Pharmacotherapy
• Rehabilitative Approaches
• Psychologic Interventions
• Anesthesia/Interventional Pain Approaches
• Neurostimulatory Techniques
• Radiotherapy
• Surgery
• Complementary/Alternative Approaches
• Lifestyle Changes

20. Opioids
• Pure (Full) Agonists: Preferred for Chronic Pain
• Bind to opioid receptor(s)
• No antagonist activity
• No ceiling effect
• Agonist-Antagonists
• Ceiling effect for analgesia
• Can reverse effects of pure agonists
✴ mixed agonist-antagonists (butorphanol,
✴ nalbuphine, pentazocine, dezocine)
✴ partial agonists (buprenorphine)
• Antagonists
• Reverse or block agonist effects of pure opioids
• Naloxone has been used to treat opioid overdose, addiction

21. Oral Opioids
Short-acting Long-acting
Hydrocodone/APAP
Transdermal fentanyl
Oxycodone +/- APAP
methadone
Morphine
morphine ER
Hydromorphone
oxycodone ER
Oral transmucosal fentanyl
Cmax ~ 45 min
Cmax and T1/2 vary based on
T1/2 ~ 4 hours
formulation and drug
Except fentanyl

22. Opioid pharmacology
• Conjugated in liver
• First pass metabolism
• Excreted by kidney (90-95%)
• First order kinetics

23. First order kinetics of opioids
6-7 min 15-20 min 45-60 min

24. Opioid pharmacology
• Conjugated by liver
• 90-95% excreted in urine
• Dehydration, renal failure, severe hepatic failure
• Decrease interval/dosing size
• If oliguria/anuria
• STOP routine dosing (basal rate) of morphine
• Use ONLY PRN

25. Delivery of opioids
What is the half life (range) for opioids?
2-4 hours
How many half lives to get to steady state?
4-5
What do you base your scheduled dosing on: Cmax or T1/2?
T1/2
What do you base your breakthrough dosing on:
Cmax or T1/2?
Cmax

26. Scheduling oral short-acting opioids
• Scheduled dosing based on t1/2
• Q4 hours
• PRN dosing based on time to Cmax
• Can be as frequent as Q1 hour PRN
• Adjust scheduled dose daily based on prn use

27. Scheduling long-acting opioids
(except methadone)
• Reason for use:
• Improve compliance, adherence
• Dose q8, q12, q24 hours (depending on product)
• Don’t crush or chew
• May use time-release granules (Kadian)
• Adjust dose every 2-4 days (once steady state is reached.)

28. Side effects of opioids
Common Uncommon
Bad dreams/hallucinations
Constipation* Delirium
Dry mouth Myoclonus
Nausea/Vomiting Seizures
Sedation Pruritus, urticaria
Sweats Respiratory suppression
Urinary retention
*No development of tolerance

29. Opioid side effects: Constipation
• Stimulant laxative:
• Senna, bisacodyl, glycerine, etc.
• Stool softener
• Docusate
• Prokinetic agent
• Metoclopramide
• Osmotic laxative (from above or below)
• Specific to peripheral opioid receptors
• methylnatrexone

30. Opioid side effects: Nausea/Vomiting
• Onset with start of opioids, tolerance may develop
• Mechanism: dopamine receptors and decreased motility
• Prevent or treat with dopamine-blocking anti-emetics (avoid with
long-QT):
• Haloperidol 0.5-1mg every 6 hours
• Droperidol 0.625 mg (PACU order set)
• Metoclopramide 10mg every 6 hours
• Alternative opioid if refractory

31. Opioid side-effects: Sedation
• Onset with start of opioids
• Distinguish from exhaustion due to pain*
• Tolerance develops within days
• Complex assessment in advanced disease
• If persistent, may consider alternative opioid or route of
administration
• Psychostimulants may play a role as well
• Methylphenidate 5mg qAM and 1 noon

32. Opioid side-effects: Neuroexcitability
• Presentation
• Cognitive changes: CAM assessment Reason to avoid “titrate
to comfort” order at end-
• acute onset or fluctuating course, of-life
• inattention,
• disorganized thinking/altered level of consciousness
• Restlessness, agitation
• Can cause hyperalgesia
• Myoclonic jerks, seizures (may be repressed if on benzodiazepines)
• More common in renal failure
• Mechanism:
• Morphine/hydromorphone 6-glucoronide build-up
• Management:
• Benzodiazepines, fluids, and perhaps dialysis - antipsychotics
exacerbate symptoms

33. Opioid side-effects: respiratory depression
• Opioid effects differ among patients
• Change in LOC occurs before respiratory suppression
• Pharmacologic tolerance develops rapidly
• Most studies of respiratory depression in opioids looked at patients
with drug overdose
• Management:
• Identify and treat contributing causes
• Reduce opioid dose and observe
• If unstable vital signs:
• Naloxone 0.1-0.2 mg IV q 1-2 min

34. Summary
• Treat pain as though it were your own:
✴remember under/untreated acute pain can lead to severe chronic pain
• Schedule routine opioids based on half-life
• Consider offering prns based on Cmax:
✴IV=6-12 min;
✴SQ=20-30min;
✴PO=45-1hour
• When ordering opioids, always order bowel regimen to avoid constipation
• Watch for neurotoxicity in renal insufficiency - especially at end-of-life