1. Module 1
Progress in Chronic Pain Management
Understanding, Impact,
Awareness and Advances
A National Pain Education Council Program

2. What is Pain?
PAIN: an unpleasant sensory and emotional
experience associated with actual or potential tissue
damage, or described in terms of such damage,
or both.
CHRONIC PAIN: persistent or recurrent pain,
lasting beyond the usual course of acute
illness or injury, or more than 6 months, and
adversely affecting the patient’s well-being.
(American Society of Anesthesiologists, 2002; Loeser et al, 2001; Merskey H et al, 1994; Portenoy et al, 1996)

3. Pain Classification Schemes
• Anatomy or Body Location (low back pain)
• Duration (acute, chronic)
• Etiology (somatogenic, psychogenic)
• Body System (e.g., myofascial, rheumatic,
causalgic)
• Severity (0-10 scale)
• Mechanism (e.g., tissue injury, nervous
system injury)
(Loeser et al, 2001)

4. Multidimensional Classification
of Pain
IASP expert multi-axial classification of chronic pain
• Axis I: Regions
• Axis II: Systems
• Axis III: Temporal Characteristics
• Axis IV: Patient’s Statement of Intensity
• Axis V: Etiology
Example:
Mild postherpetic neuralgia of T5 or T 6; 6 months’ duration = 303.22e
Axis I: Thoracic region
Axis II: Nervous system (central, peripheral, or autonomic); physical
disturbance/dysfunction
Axis III: Continuous or nearly continuous, fluctuating severity
Axis IV: Mild severity of 1 to 6 months
Axis V: Trauma, operation, burns, infective, parasitic (one of these)
(Loeser et al, 2001; Merskey et al, 1994)

5. Prevalence and Impact
of Chronic Pain on Society
• Chronic pain is one of the most common conditions
for which people seek medical treatment
• 35% of Americans suffer from chronic pain
• >50 million Americans are partially or totally
disabled by chronic pain
• 50 million workdays are lost per year
• $100 billion is the estimated annual cost in lost
productivity, medical costs, and lost income
(American Pain Society, 2001; Gitlin, 1999; Glajchen 2001; Loesser et al, 2001)

6. Undertreatment of Chronic Pain
• >40% to 50% of patients in routine practice
settings fail to achieve adequate pain relief
• In a recent study of 805 chronic pain
sufferers, >50% had to change physicians to
achieve relief because the physician:
– was unwilling to treat pain aggressively
– did not take the patient’s pain seriously
– had inadequate knowledge about pain
treatment
(American Pain Society, 2001; Glajchen, 2001; Lister, 1996; Portenoy, 1996)

7. Common Barriers to
Treatment of Chronic Pain
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)

8. Ethnic and Racial Barriers
to Treatment
• Language or cultural differences make pain
assessment more difficult
• Physicians’ 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)

9. Evolving Attitudes Toward
Opioid Use
Historically, opioids were emphasized in terminally ill patients, and
de-emphasized in chronic nonmalignant pain management.
However, from the 1980’s to the present :
• Attitudinal/perceptual changes on opioid use in
nonmalignant chronic-pain treatment
• More use of long-term opioid therapy in diverse pain syndromes
– slowly growing evidence base
– acceptance by pain specialists
– acceptance by government and medical associations
– increased reassurance from the regulatory community
(Joranson et al, 2000; Portenoy et al, 1986)

10. Recent Developments
In Pain Management
• Greater understanding of the pathophysiology
underlying chronic pain syndromes
• Scientific breakthroughs in molecular biololgy; insight
into pain at the molecular level
• Advances in drug therapy (drug delivery technologies)
• Multimodal therapy
• Multidisciplinary teams, shared decision-making that
includes patients
• Patients’ rights movement
(JCAHO, 1999; Loeser et al, 2001)

11. Recent Organized Support for
the Treatment of Pain
National Organizations Issue Guideines
• U.S. Agency for Health Care Policy and Research (HCPR)—1992
• U.S. Department of Health and Human Services—1994
• AAPM/APS Consensus Statement—1996
• American Society of Anesthesiologists—1997
• WHO; FSMB—1998
• AMA; APS (sickle-cell anemia)—1999
• American Pain Society: Clinical Guideline for Arthritis—2002
State-Led Initiatives
• Legislation in form of Intractable Pain Acts (>10 states by 1999)
• Guidelines for pain management (>18 states by 1999)
• State Cancer Pain Initiatives
(AAPM/APS, 1996; AMA, 2001; ASA, 1997; FSMB, 1998; JCAHO, 1999; WHO, 1996)

12. Module 2
Progress in Chronic Pain Management
Chronic Pain Syndromes:
Cancer
Chronic Low Back Pain
Osteoarthritis
Fibromyalgia
A National Pain Education Council Program

13. Cancer Pain
Epidemiology
• Cancer pain is highly prevalent
– 30%-50% of those in active therapy
– 75%-90% of those with advanced disease
– approximately 25% of those in nursing
homes
(Bernebei et al, 1998; Caraceni et al,1999; Cleeland et al, 1994; Heim et al, 1993; Portenoy, 1994; Portenoy et al, 1992;
Serlin et al, 1995)

14. Cancer Pain
Inferred Pathophysiology
• Nociceptive: deemed consistent with apparent
degree of tissue injury
– Somatic: related to ongoing activation of
somatic primary afferents
– Visceral: related to activation of primary
afferent neurons that innervate viscera
• Neuropathic: sustained by aberrant
somatosensory processing in the peripheral
nervous system or CNS
(Portenoy, 2000)

15. Cancer Pain
Diagnosis: Clinical Considerations
• Acute or chronic
• Nociceptive, neuropathic or mixed pain
– tumor-related (e.g., metastatic bone disease,
nerve compression or infiltration)
– treatment-related (chemotherapy, radiation or
surgery)
– unrelated to cancer or treatment
(Portenoy , 2000; Portenoy et al, 1996)

16. Cancer Pain
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
(Cleeland CS et al, 1992; Jacox et al, 1994; Portenoy et al, 199; Turk et al, 1994; Wall et al, 1994)

17. 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 opoids
– adjuvant medications for neuropathic pain
– NSAIDs and steroids can be helpful when there is an
inflammatory component to pain
(Jacox et al, 1994)

18. WHO Guidelines for Cancer Pain
GOAL:
Freedom From Pain
STEP 3 • Step 3: Opioids for
moderate-to-severe pain +/-
non-opioid +/-adjuvant
Pain Persists therapy
STEP 2 • Step 2: Opioids for mild- to-
moderate pain +/- non-
Pain Persists opioid +/- adjuvant therapy
• Step 1: Non-opioid +/-
STEP 1 adjuvant therapy
08/13/12
(Adapted from Portenoy et al, 1997)

19. Chronic Low Back Pain
Epidemiology
• 60%–85% lifetime prevalence
• Second most common complaint to prompt medical
evaluation
• Leading cause of long-term work disability
• Most common reason for early Social Security disability in
US
• U.S. indirect costs: $33 billion annually
• Disability and costs related to pain, not to the disease
process
(Loesser et al, 2001; Wall et al, 1994)

20. Chronic Low Back Pain
Pathophysiology
• Activation and sensitization of the nerve root
nervi nervorum from root compression/traction
• Sensitization of the nociceptors of the annulus
fibrosus, periosteal spinal structures, and
ligaments, due to acute inflammation, e.g.,
status post-trauma
• Hyperalgesia (deep spinal and dermatomal)
due to central sensitization
(Loesser et al, 2001)

21. Chronic Low Back Pain
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
(Wall et al, 1994)

22. Chronic Low Back Pain
Diagnosis
• History
– medical, psychosocial
– pain: location, duration, severity, alleviating/
aggravating influences
• Physical Examination
– posture and range-of-motion evaluation
– routine neurologic and vascular exams
• Imaging Studies
– X-rays with flexion/extension
– MRI
– CT in some
(Wall et al, 1994)

23. Chronic Low Back Pain
Treatment Considerations
• Analgesic Medications
• Adjuvant Analgesics
• Physical Therapy Approaches
• Neural Stimulation
• Psychologic Management
• Multidisciplinary Pain Centers
(Portenoy et al, 1994)

24. Osteoarthritis
(Degenerative Joint Disease)
Epidemology
• Most common form of arthritis worldwide
• Occurs most in women and in adults over age 45
• Occurs in 80% of people over 55 years of age
• Affects >40 million people in US (1 in 6)
• 23% experience limitation of activities
• Cost in medical care and lost wages ~$95 billion
(Elders, 2000; Loeser et al, 2001; Merskey et al, 1994)

25. Osteoarthritis
Pathophysiology
• Progressive loss of articular cartilage
• Chondrocytes produce metalloproteinases that
degrade cartilage and cause fissuring, pitting,
erosion, and denuded areas
• Subchondral bone thickens and osteophytes, or
bone spurs, form
• Synovium thickened (contains moderate amount
of lymphocytes, plasma cells)
• Joint capsule and ligaments hypertrophied
(Loesser et al, 2001; Wall et al, 1994)

26. Osteoarthritis
Clinical Characteristics
• Deep aching pain, poorly localized
• May occur in one or two joints or be generalized
• Pain occurs in involved joint and is relieved by rest
• Joint stiffness in morning and after periods of inactivity
• Aching “night pain” is common
• If pain is severe on activity and asymptomatic at rest,
evaluate for neurogenic claudication
(Loesser et al, 2001)

27. Osteoarthritis
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
(Loesser et al, 2001; Manek et al, 2000)

28. Osteoarthritis
Treatment Considerations: First, perform a
comprehensive assessment of pain and function
Mild-to-moderate pain Acetaminophen
Moderate-to-severe pain COX-2 NSAIDS
Severe arthritis pain: COX-2 Opioids
drugs and non-specific
NSAIDs do not provide
substantial relief
Drug therapy ineffective and Surgical Treatment
function severely impaired
(ACR, 2000; APS, 2002; Manek et al, 2000)

29. Fibromyalgia Syndrome
Epidemiology
• 4–7 times more common in adult women than in
men; highest prevalence in women 50–60 yrs
• Approximately 2% of general population in U.S.
and Canada have symptoms that could meet
ACR criteria
• Long-term follow-up studies suggest that
fibromyalgia is not a syndrome representing a
transition from one disorder to another
(Loesser et al, 2001; Portenoy et al, 1996; Wall et al, 1994)

30. Fibromyalgia Syndrome
Pathophysiology
Etiology is unknown: 3 views of pathophysiology have emerged:
• Central Nervous System (neurogenic)
– generalized pain
– increase in CSF substance P
– decrease in serum and CSF serotonin
• Muscle Pathology
– decreased oxygen tension and blood flow
– abnormal muscle biopsies
– weakness
• Psychopathology
– anxiety, depression
(Loeser et al, 2001; Portenoy et al, 1996; Wall et al, 1994)

31. Fibromyalgia Syndrome
Clinical Characteristics
• Pain (musculoskeletal tenderness)
• Lightheadedness, dizziness, syncope
• Fatigue
• Chronic insomnia; sleep disturbance
• Cognitive deficits/short-term memory loss
• Depression/anxiety
• Numbness, dysesthesia in hands and feet
(Loeser et al, 2001)

32. Fibromyalgia Syndrome
Diagnosis
Based on the 1990 ACR
classification guidelines:
• 1 historical feature + 1 physical finding
• Historical feature = widespread (axial) pain
of 3 months or more
• Physical finding = pain in at least 3 of the 4 body
segments + a finding of at least 11 tender points on
digital palpation of 18 designated tender points
(Merskey et al, 1994; Portenoy et al, 1996; Wall et al, 1994; Wolk M, 2002)

33. Fibromyalgia Syndrome
Treatment: A Multidisciplinary Approach
• Patient Education
– reading materials, videos, support groups
• Physical Exercise
– low-grade (muscle stretches, aerobic conditioning)
• Pharmacologic Therapies
– tricyclic antidepressants, NSAIDS, topical
capsaicin, opioids*
*Drug therapies have been used with varying degrees of success in
treating fibromyalgia.
(Portenoy et al, 1996; Wall et al, 1994)

34. Pathophysiology of Pain
• Inferred from characteristics, etiology or
pathophysiology
• Types
– nociceptive
– neuropathic
– idiopathic
• Therapeutic implications
(Portenoy et al, 1996)

35. Pathophysiology of 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
(Marcus, 2000)

36. Peripheral and Central Pathways for Pain
Ascending Tracts Descending Tracts
Cortex
Thalamus
Midbrain
Pons
Medulla
Spinal Cord
(Brookoff, 2000)

37. Pain-Sensing System in the
Malfunction in Chronic Pain
Pain Acute pain:
Sensing Pain-sensing signals are
initiated in response to a
In chronic pain, stimulus
pain signals are • They elicit a pain-
generated relieving response
without
physiologic
significance Chronic pain:
Pain signals are
generated for no reason
and may be intensified
• Pain-relieving
mechanisms may be
defective or
deactivated
(Illustration: Seward Hung, 2000)

38. Nociceptive Pain
Presumably results from ongoing activation of primary
afferent neurons responding to noxious stimuli
• Pain consistent with degree of tissue injury
• Described as aching, squeezing, stabbing, throbbing
• Subtypes:
– Somatic: related to activation of somatic afferent
neurons
– Visceral: related to activation of visceral afferent
neurons
(Loeser et al, 2001; Portenoy et al, 1996)

39. Neuropathic Pain
• Initiated by a primary lesion in the nervous system; believed to be
sustained by aberrant somatosensory processing in the peripheral or
central nervous system
• Independent of obvious ongoing nociceptive activation
• Burning, shooting, electrical quality; may be aching, throbbing, sharp
• Subtypes:
– Presumed “central generator”
 deafferentation pain (central pain, phantom pain)
 Sympathetically-maintained pain
– Presumed “peripheral generator”
 Polyneuropathies and mononeuropathies
(Portenoy et al, 1996)

40. Idiopathic and Psychogenic Pain
Idiopathic Pain
• Usually exists in the absence of an identifiable physical or
psychologic pathology that could account for pain
• Uncommon in patients with progressive illness
Psychogenic Pain
• Presents positive evidence of a predominant psychologic
contribution and may be labeled with a specific
psychiatric diagnosis
(Loeser et al, 2001; Merskey et al, 1994; Portenoy et al, 1996)

41. Module 3
Progress in Chronic Pain Management:
Therapeutic Modalities for
Chronic Pain Management
Assessment
A National Pain Education Council Program

42. Pain Assessment
• Characterize the pain
• Characterize the disease, relationship between
pain and disease and potentially treatable
etiologies
• Clarify syndromes and infer pathophysiology
• Determine need for urgent therapy
• Identify other needs
• Develop a therapeutic strategy
(Portenoy et al, 1997)

43. Pain Assessment
Components
• History: temporal features, intensity, topography, quality,
exacerbating/alleviating factors
• Physical Exam: determine existence of underlying
pathology
• Lab and Radiographic Tests: appropriate to pain
syndrome
Assessment Tools
• Pain Intensity Scales: VAS, NAS, “faces” scale
• Multidimensional Pain Measures: Brief Pain Inventory,
McGill Pain Questionnaire
(Portenoy et al, 1997)

44. Pain Intensity Rating Scales
• Visual Analogue Scale (VAS)
No pain ----------------------------------- Worst pain
• Numerical Rating Scale
0 ------------------------------------------- 10
No pain Worst pain
imaginable
• Categorical Scale
None (0) Mild (1 – 4) Moderate (5 – 6) Severe (7 – 10)
(Cleeland, 1991; Jacox et al, 1994)

45. Pain Intensity Rating Scales
• Pain Faces Scale
0 2 4 6 8 10
No Hurts Hurts a Hurts Hurts a Hurts as
hurt just a little bit even whole much as
little bit more more lot you can
imagine
• Brief Pain Inventory
Shade areas of worst pain
Put an X on area that hurts most
(Cleeland, 1991; Wong et al, 2001)

46. Module 3
Progress in Chronic Pain Management
Therapeutic Modalities for
Chronic Pain Management:
Treatment
A National Pain Education Council Program

47. Therapeutic Options
for Chronic Pain Management
• Pharmacotherapy
• Rehabilitative Approaches
• Psychologic Interventions
• Anesthesiological Approaches
• Neurostimulatory Techniques
• Surgery
• Complementary/Alternative Approaches
• Lifestyle Changes
(Portenoy et al, 1997)

48. Chronic Pain Management:
Pharmacotherapy
Analgesics
• Nonopioids
• Adjuvant Analgesics
• Opioids
(Cashman, 1996; Hanks et al, 1998; Galer, 1998; Stein, 1995)

49. Nonopioid Analgesics:
Acetaminophen
• Minimal anti-inflammatory effect
• Fewer adverse effects than other nonopioid
analgesics
• Adverse effects:
– renal toxicity
– risk of hepatotoxicity at high doses;
• increased risk with liver disease or chronic
alcoholism
• No effect on platelet function
(Gilman et al, 2001)

50. Nonopioid Analgesics:
NSAIDS
Mechanism of Action
• Inhibit both peripheral and central cyclo-
oxygenase, reducing prostaglandin formation
• 2 isoforms of COX
– COX-1: Constitutive, physiologic
– COX-2: Inducible, inflammatory

51. Nonopioid Analgesics:
NSAIDS
• Major recent advance: COX-2 selective NSAIDS
• COX-2 selective inhibitors have better GI safety profile;
no change in platelet function
• Drug selection should be influenced by drug-selective
toxicities, prior experience, convenience, cost
• Great individual variation in response to different drugs
• Use with caution in patients with renal insufficiency,
congestive heart failure or volume overload
(Cashman, 1996: Langman et al, 1999; Simon et al, 1999)

52. Adjuvant Analgesics
Adjuvant Analgesics for Neuropathic Pain
CLASS EXAMPLES
Anticonvulsants gabapentin, valproate, phenytoin,
carbamazepine, clonazepam,
topiramate, lamotrigine
Antidepressants amitriptyline, desipramine, nortrip-
tyline, paroxetine, citalopram, others
Local Anesthetics mexiletine
Corticosteroids dexamethasone, prednisone
α-2 Adrenergic Agonists tizanidine
NMDA-Receptor Agonists dextromethorphan, ketamine
Topicals lidocaine, lidocaine/prilocaine, capsaicin
Miscellaneous baclofen, calcitonin

53. Adjuvant Analgesics:
Anticonvulsants
Common Characteristics
• Most clinical experience: gabapentin, carbamazepine, phenytoin, valproate, clonazepam
• Limited data on efficacy of newer anticonvulsants
• Used as an analgesic, dosing schedule is similar to anticonvulsant indication
• Large inter-/intra-individual variability in analgesic response
Gabapentin
• Usual first-line drug for neuropathic pain
• Favorable safety profile
• Positive controlled trials in PHN/diabetic neuropathy
• No controlled studies in cancer patients
• Usual starting dose 100-300 mg/day
• Titration to identify responders/nonresponders
• Usual effective dose 600-3600 mg/day; higher doses sometimes beneficial
(Galer, 1998; Rosner et al, 1996)

54. Adjuvant Analgesics:
Antidepressants
• Evidence is best for tricyclics
• SSRI/atypical antidepressants better tolerated
• Proven efficacy for all types of neuropathic
pain, but often preferred for continuous
dysesthesias
• Analgesic doses for tricyclics is usually less
than the antidepressant dose
(Wall et al, 1999)

55. Adjuvant Analgesics:
Corticosteroids
• Shown to improve pain, appetite, nausea, malaise,
quality of life in cancer patients
• In the cancer population, indicated for refractory
neuropathic pain, and other indications: bone pain,
bowel obstruction, capsular pain, lymphedema,
headache
• In non-cancer pain, long-term use is limited to
inflammatory conditions
• Usual drugs are prednisone and dexamethasone
(Lucas et al, 2002)

56. Adjuvant Analgesics:
α-2 Adrenergic Agonists
• Evidence of nonspecific analgesic effects
• Established analgesic effect of epidural
clonidine in neuropathic cancer pain
• Tizanidine usually better tolerated (starting
dose 1-2 mg/day; usual maximum dose up to
40 mg/day)
(Max et al, 1992; Sindrup et al, 990)

57. Adjuvant Analgesics:
NMDA-Receptor Antagonists
• N-methyl-D-aspartate receptor involved in
neuropathic pain
• Commercially-available drugs in the U.S.:
ketamine, dextromethorphan, amantadine
– Ketamine: dissociative anesthetic; can be used
p.o. or IV/SC infusion
– Dextromethorphan: antitussive; starting dose 120
mg/day; maximum daily dosage one gram
– Amantadine: starting does 100 mg b.i.d.
(Herry et al, 1995; Nelson et al, 1997; Pud et al, 1998)

58. Opioid Therapy: Classes of
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
(Jacoxet al, 1994; Portenoy et al, 1996)

59. Opioid Therapy: Drug Selection
Short-Acting Opioids Long-Acting Opioids
• Hydrocodone/APAP • Transdermal Fentanyl
• Hydromorphone • Methadone
• Morphine • Extended-release
• Oxycodone w or w/o morphine
APAP • Oxycodone CR
• Oral transmucosal
fentanyl
• Tramadol
(Lucas et al, 2002)

60. Opioid Therapy: Drug Selection
Advantages of Long-Acting Opioids
• Fewer peaks and troughs
– sustained pain relief
• Dosed less often, improved adherence
• Potentially improved patient satisfaction
and quality of life
(Lucas et al, 2002; Weinstein et al, 2001)

61. Opioid Therapy:
Prescribing Principles
• Drug Selection: Elements to Consider
– Severity of pain, previous exposure, availability,
patient’s preference, renal/liver function, cost
• Dose to Optimize Effects
– Fixed schedule (or around-the-clock) vs as-needed
dosing; rescue doses
• Treat Side Effects
– Goal: balance between analgesia and side effects
• Manage the Poorly Responsive Patient
– Consider a variety of alternative strategies
(Weinstein et al, 2002)

62. Opioid Therapy:
Route of Administration
• Oral / Transdermal
• Rectal
• Parenteral (IV, SC)
• Intraspinal (epidural, intrathecal)
(Lucas et al, 2002)

63. Opioid Therapy: Dosing
• By-the-clock (fixed-schedule) dosing with
long-acting opioid plus an “as-needed” short-
acting “rescue” opioid (usually 5%–15% of
total daily dose, q 2-3 h prn)
• Baseline dose increases: 25%–100% or
equal to “rescue” dose use
• Increase “rescue” dose as baseline dose
increases
(American Pain Society, 1998)

64. Equianalgesic Table
PO/PR (mg) Analgesic SC/IV/IM (mg)
30 Morphine 10
4–8 Hydromorphone 1.5
20 Oxycodone -
20 Methadone 10
- Fentanyl 100 μg/h parenterally and
transdermally ≡ 4 mg/h
morphine parenterally;
1 μg/h transdermally ≡
2mg/24h morphine PO

65. Equianalgesic Conversions
Example:
• Patient receiving a total 24-hr dose of morphine 180 mg PO
• What is the equivalent 24-hour dose of PO
hydromorphone?
• Morphine 30 mg PO = Morphine 180 mg PO
• Hydromorphone 7.5mg PO X
• X = Hydromorphone 45 mg PO (6-8mg PO q 4hr)
• Determine starting dose of new drug based on this
calculation

66. Conversion Chart for Starting Dose
of Transdermal Fentanyl
Fixed-combination short-acting
opioids (6/day):
– Lorcet 5 mg/500 mg
– Lortab 5 mg/500 mg
– Percocet 5 mg/325 mg One 25 mcg/h
– Percodan 5 mg/325 mg transdermal
– Tylenol + Codeine 30 mg/325 mg fentanyl
– Tylox 5 mg/500 mg patch/3 days
– Vicodin 5 mg/500 mg (72 hours)
Long-acting opioids(2/day):
Multiple patches may be used
– OxyContin 20 mg for doses exceeding 100 mcg/h.
Doses up to 6oo mcg/h have
– MS Contin 30 mg been evaluated in clinical trials.
(Adapted from Duragesic PI, 2001)

67. Opioid Titration
• Dose titration over time is key to successful opioid
therapy
• There is no ceiling dose for pure-agonist opioids.
Titrate dose upward for maximum pain relief with
acceptable side effects
• Consider rescue medication for breakthrough pain
• Responsiveness of an each patient to each drug
varies
• If a patient does not respond well on one opioid, it is
important to try another (opioid rotation)
(Portenoy et al, 1997)

68. Opioid Therapy: Patient Selection
• Thorough Evaluation
– pain history
– physical exam
– coexisting conditions
• Review of Previous Medical/Pain History
– any psychological disturbances
– chronic pain history
• Substance Abuse History (including alcohol)
– remote, recent or ongoing
– patient goals/expectations
• consistent with physician’s?
• feasible/reasonable?
(Haddox et al, 1997; Portenoy et al, 1996)

69. Opioid Therapy:
Monitoring Outcomes
Monitoring the 4 A’s
• Analgesia (pain relief)
• Activities of Daily Living (psychosocial
functioning)
• Adverse Effects (side effects)
• Aberrant Drug-Taking (addiction-related
outcomes)
(American Pain Society, 2002; Passik et al, 2000; Portenoy et al, 1997)

70. Opioid Therapy: Managing the
Poorly Responsive Patient
If dose escalation increases adverse effects
• Side-effect management
• Pharmacologic strategy to lower opioid requirement
– spinal route of administration
– add nonopioid or adjuvant analgesic
• “Opioid rotation”
– nonpharmacologic strategy to lower opioid
requirement
(Mather, 2001)

71. Opioid Therapy: Managing the
Poorly Responsive Patient
Opioid Rotation
• Based on large intra-individual variation in response
to different opioids
• Reduce equianalgesic dose by 25%–50% with
provisos:
– reduce less if pain severe
– reduce more if medically frail
– reduce less if same drug by different route
– reduce transdermal fentanyl less (no cutback
from equianalgesic dose)
– reduce methadone more: 75%–90%
(Indelicato et al, 2002; Mather, 2001)

72. Opioid Therapy:
Managing Side Effects
• Common
– Constipation
– Somnolence, mental clouding
• Less Common
– Nausea – Sweating
– Myoclonus – Amenorrhea
– Itch – Sexual dysfunction
– Urinary retention – Headache
(Ahmedzai et al, 1997; Portenoy, 1996)

73. Novel Drug Therapies for
Treatment of Pain
Central Nociception:
Emerging Analgesic Targets
• Excitatory amino acid and NK receptors
• N-type Ca++ receptors
• N-acetylcholine receptors
• Adenosine (A1) receptors
• Cannabinoid (CB1) receptors
(Pappagallo M)

74. Novel Drug Therapies for
Treatment of Pain
Peripheral Nociception:
Emerging Analgesic Targets
• Sensory neuron specific Na+ channels (eg, PN3, NAN)
• Opioid receptors
• Vanilloid receptors
• Serotonin receptors
• Alpha-adrenergic receptors
• Proton-sensitive channels (pH-sensitive)
• Nerve–growth-factor receptors (*TrKA, p75)
• N- or T-type Ca++ channels
• Purine receptors
*TrKA = tyrosine kinase
(Pappagallo M)

75. Chronic Pain Management:
Nonpharmacologic Approaches
Anesthetic Approaches
• Neuraxial Drug Administration
– opioids, local anesthetics, and/or clonidine
via continuous epidural or intrathecal
infusion
• Neural Blockade
– temporary block
– neurolytic block
(Eisenach et al, 1995; Patt et al, 1998)

76. Chronic Pain Management:
Nonpharmacologic Approaches
Neurostimulatory Approaches
• TENS (transcutaneous electrical nerve stimulation)
• Acupuncture
• Dorsal Column Stimulation
Surgical Procedures
• Peripheral Nerve Procedures
– peripheral neurectomy
– rhizotomy
• CNS Procedures
– cordotomy
(Portenoy et al, 1996)

77. Chronic Pain Management:
Nonpharmacologic Approaches
Psychologic Treatments
• Behavioral treatment
• Biofeedback
• Cognitive-Behavioral Treatment
Rehabilitative Approaches
• Physical/Occupational Therapy
• Heat/Cold Therapy (diathermy, cryotherapy)
• Prostheses
• Assistive Devices
(Redd et al, 2002)

78. Module 4
Progress in Chronic Pain Management
Substance Abuse Issues in
Chronic Pain Management
A National Pain Education Council Program

79. The Terminology of Abuse
• Physical Dependence
– Abstinence syndrome induced by administration of an antagonist
or by dose reduction
– Usually unimportant if abstinence is avoided
– Assumed to exist after few days’ dosing but actually highly variable
– Does not independently cause addiction
• Addiction
– Disease with pharmacologic, genetic, psychosocial elements
– Fundamental features: loss of control, compulsive use, use
despite harm
– Diagnosed by observation of aberrant drug-related behavior
(AAPM/APS, 1996; NIDA, 2001; Passik et al, 2000; Portenoy, 1996)

80. The Terminology of Abuse
• Tolerance
– Diminished drug effect from drug exposure
– Varied types: associative vs. pharmacological
– Tolerance to analgesia is seldom a problem in the clinical setting:
• Tolerance rarely “drives” dose escalation
• Tolerance does not cause addiction
• Pseudoaddiction
– Aberrant drug-related behaviors driven by uncontrolled pain
– Reduced by improved pain control
– Complexities
• How aberrant can behavior be before it is inconsistent with
pseudoaddiction?
• Can addiction and pseudoaddiction coexist?
(Passik et al, 1998; Passik et al; Portenoy RK, 1996)

81. Risk Assessment for Addiction
Low Addiction Risk
• Acute pain
• Cancer pain
• Patients without abuse background or psychopathology
Chronic Noncancer Pain
• Probability of addiction is small
– surveys that include patients with abuse or
psychopathology show mixed results
• Predictors of addiction may include
– history of substance abuse
– Age
– personality factors
– family dynamics and social factors
(Passik et at, 1998; Passik et al, 1998)

82. Diagnosing and Monitoring
Aberrant Behaviors
Two-Step Monitoring Approach
• Step 1: Are there aberrant drug-related aberrant behaviors?
• Step 2: If yes, are these behaviors best explained by the
existence of an addiction disorder?
Differential Diagnosis
• Addiction/pseudoaddiction
• Other psychiatric disorders (e.g., borderline personality
disorder)
• Mild encephalopathy
• Family disturbances
• Criminal intent
(Passik et at, 1998; Passik et al, 1998)

83. Drug-Related Behavior
Predictive of Addiction
Probably More Predictive Probably Less Predictive
• Selling prescription drugs • Aggressive complaining
• Prescription forgery • Drug hoarding when symptoms
• Stealing or “borrowing” drug from milder
another person • Requesting specific drugs
• Injecting oral formulation • Acquisition of drugs from other
• Obtaining prescription drugs from medical sources
non-medical source
• Unsanctioned dose escalation
• Multiple episodes of prescription
“loss”
once or twice
• Concurrent abuse of related illicit • Unapproved use of the drug to
drugs treat another symptom
• Multiple dose escalations despite • Reporting psychic effects not
warnings intended by the clinician
• Repeated episodes of gross • Occasional impairment
impairment or dishevelment
(Passik et al, 1998)

84. Addressing Aberrant
Drug-Related Behavior
• General Management Principles
– know laws and regulations
– structure therapy to match perceived risk
• Proactive Strategies
– communicate goals of therapy
– provide written guidelines (treatment contract)
– assess often
• Reactive Strategies
– require frequent visits and small quantities of drug
– use of urine toxicologies
– long-acting drugs with no rescue doses
– relate to addiction-medicine community (sponsor, program,
addiction-medicine specialist, psychotherapist)
(Mironer et al, 2000; Portenoy et al, 1997; Passik et al, 2000)

85. Conclusions
• Chronic pain is common and undertreated
• Identify chronic pain patients who would most likely
benefit from opioid therapy and use it responsibly
• Implement opioid treatment with a plan for ongoing
monitoring
• Assess and monitor pain, side effects, and drug-related
behaviors
• Adjust dosage
• Manage side effects