Principles of Pain
Management in Non-terminal
Pain
Muhammad A. Munir, MD
Diplomat American Board of Anesthesiology and Pain
Management
Principles of Pain Management
• Approaches
– Give them what they want
– Give them what you want
– Don’t give them anything just send them to the pain
clinic!
– Give them what they want (and send them to the pain
clinic!!)
– Mechanistic Approach
Mechanistic Approach to Pain
Management
• Etiology
– Primary Consideration
• Acute vs Chronic
• Nociceptive vs Neuropathic
– Secondary Consideration
• Cancer vs Non-Cancer Pain
• Static vs changing
• Treatment Endpoint
• Management Options
Acute Pain is a
Warning Symptom
of Underlying
Problems
Acute Pain Management
• Clear Etiology
– Perioperative Pain
– Acute Illness or Injury
– Acute on Chronic Pain
• Clear Treatment Endpoint
• Straight forward management options
– Multimodal Treatment Approach
– NSAIDs, Adjuvants, Opioids and Neural Blockade
Chronic Pain Syndrome:
Any Referral Preceded
by an Apology
Chronic Pain Management
• Complex Etiology
– Chronic nociceptive pain?
– Neuropathic pain
– Central sensitization and neuronal plasticity
• Treatment Endpoint?
• Controversial Pain Management Options
– Role of Opioids
– Multidisciplinary Pain Management
Nociceptive Pain
• Results from mechanical, thermal, or chemical
excitation of peripheral nerve fibers (normal neuronal
activity)
• Mediated at nociceptors widely distributed in
cutaneous tissue, bone, muscle, connective tissue,
vessels, and viscera
• Pain described as dull, aching, throbbing, sometimes
sharp
• Typically Opioid responsive
• Examples
– Bone pain
– Colicky pain
– Pain ellicited by tissue injury
Krames E, 1996
Neuropathic Pain
• Results from damage to the peripheral or central
nervous system (abnormal neuronal activity)
• Possibly involvement of NMDA receptors
• Pain described as burning, tingling, shooting, electriclike, or lightning-like.
• May exhibit opioid resistance or require higher doses
for effect.
• Examples
–
–
–
–
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PHN
Peripheral neuropathies
Complex regional pain syndrome
Plexopathies
mononeuropathies
Cancer Pain
• Complex Etiology
–
–
–
–
Dynamic and progressive nociceptive pain
Neuropathic component
Central Sensitization
Psychological Impairment
• Treatment Endpoint
• Management Options
– Opioids are mainstay of therapy
– Neural Blockade, Neuromodulation and
Neuroablative techniques.
– Multidisciplinary Approach
Non-Cancer Pain (non-terminal)
• Etiology
– Nociceptive with central sensitization and neuronal
plasticity
– Neuropathic Pain
– Mixed nociceptive and neuropathic pain
– Psychological Impairment
• Treatment Endpoint?
• Management Options for chronic Non-Cancer
Pain???
Chronic Non-Cancer Pain
• 15-33% of US Population or as many as 70
Million People are affected by chronic pain.
• Disables more people than both Cancer and
Heart Disease combined
• Costs more than both Cancer and Heart disease
• $100 billion dollars annually in medical costs,
lost working days and workers compensation.
– 2 times more than the budget of Israel
– In fact only 16 Countries in the World have budget
over 100 billion for year 2005!!
Management Options for Non-Cancer
Pain
• Desired Outcomes?
– Good Pain Control
– Improved Function
– Improved Quality of life
– Or a combination of all of the above with
acceptable Liabilities?
Chronic Pain Management
Multidisciplinary Pain Medicine
• Treatments offered
– Medical/Pharmacological
– Interventional
– Psychological/Central processing
– Physical
– Surgical
Multidisciplinary Pain Medicine
Medical Management
• Opioid Analgesics
• Non-Opioid Analgesics
• Adjuvant Medication
Medical Management
WHO’s Pain Relief Ladder
•
•
To maintain freedom from pain, drugs
should be given “by the clock”, that is
every 3-6 hours, rather than “on
demand” This three-step approach of
administering the right drug in the
right dose at the right time is
inexpensive and 80-90% effective.
Surgical intervention on appropriate
nerves may provide further pain relief if
drugs are not wholly effective.
WHO: Cancer pain relief and palliative
care: Report of a WHO expert committee.
Geneva, World Health Organization, 1990
(technical report series, no. 804)
Medical Management
Opioid Therapy for Non-cancer Pain
• “The World Health Organization has published a "threestep ladder" guide to treatment of cancer pain graded
from mild to severe; this guide can be readily applied to
the treatment of pain from all sources…..”
• “Opioid analgesics are the mainstay of treatment for
moderate to severe pain….”
“Using Opioid Analgesics to Manage Chronic Noncancer Pain in
Primary Care”. J Am Board Fam Pract 12(4):293-306, 1999
Medical Management
Opioid Therapy for Non-cancer Pain
• Efficacy
– Short-term Analgesic efficacy
– Long-term Analgesic efficacy
• Function and Quality of Life Improvement
• Liabilities
– Hormonal and Immune system effects
– Tolerance, Hyperalgesia, Dependence and Addiction
Opioid Therapy for Non-cancer Pain
Analgesic Efficacy
• Short-term analgesic efficacy
– Over 18 RCT have advocated analgesic efficacy of
opioids for up to 8 months (Most ranging between 412 weeks)
– Types of Pain include
•
•
•
•
•
OA
RA
Musculoskeletal
Mixed nociceptive and neuropathic
Back pain
Opioid Therapy for Non-cancer Pain
Analgesic Efficacy
• Long-term analgesic efficacy
– No RCT for longer than 8 months1
– Open-label follow-up studies report
satisfactory analgesia
• 56% of patients abandon the treatment2
– Long term Therapy has been based on
escalating doses to overcome
pharmacological tolerance
Haythornthwaite, JA et al. J Pain Symptom Management 1998;15:185-94
Kalso, E et al. Pain 2004;112:372-80
Opioid Therapy for Non-cancer Pain
Function and Quality of Life
• Scarce Data on Functional Improvement
• Case Series, report Improvement in Function and QOL
• RCT are less Clear
– 11 RCTs show improvement
– 7 RCTs show no improvement despite better pain scores
• Limitations
– Functional Testing Varies among RCTs (physical function, joint
tenderness, hand grip vs sleep, anxiety, disability status)
– Current RCTs are limited up to 8 month follow up.
Opioid Therapy for Non-cancer Pain
Liabilities
• Hormonal Effects
– Hypogonadotropic hypogonadism,(100%)
– Central hypocorticism, (15%)
– GH deficiency (15% ).
• Immune System
– Natural Killer Cell suppression
– Polymorphonuclear cell and Macrophage Phagocytic Function
• Opioid induced Hyperalgesia
• Tolerance, Dependence, and Addiction
Abs et al. J Clin Endocrinol Metab. 85 (6): 2215.
Yeager, M Anesthesiology. 83(3):500-508, September 1995
Vanderah J el al. Neurosci 2000;20:7074–9.
Mao J. Pain 2002;100:213–7.
Opioid Therapy for Non-cancer Pain
Addiction
• DSM-IV criteria for addiction
• A maladaptive pattern of substance use, leading to
clinically significant impairment or distress, as
manifested by 3 or more of the following present at any
time in the same 12 month period
– Tolerance
– Withdrawal
– Substance taken in larger amount and for longer duration then
intended
– Persistent desire or unsuccessful effort to cut down
– Great deal of time spent in acquisition, use or in recovery
– Important social, occupational and recreational activities given
up because of substance abuse
– Continued substance use despite knowledge of physical or
psychological harm
Opioid Therapy for Non-cancer Pain
Addiction
• APS, AAPM and ASAM Consensus
statement defining addiction in patient
using opioids for pain
– Impaired control over drug use
– Compulsive use
– Continued use despite harm
– Craving
Opioid Therapy for Non-cancer Pain
Addiction
• Incidence
– Low rate of addiction (0.03%)1
• Hospitalized patients
– High rate of addiction (18.9%)2
• Systemetic review
– Realistic Rate of addiction (~5%)
Porter J, Jick H. Addiction rare in patients treated with narcotics (letter). N Engl J Med
1980;302
Fishbain, DA et al. Drug abuse, dependence and addiction in chronic pain patients. Clin J
Pain 1992;8;77-85
Pharmacological Therapy
Opioid Therapy for Non-cancer
Pain
•
•
•
•
Treatment Algorithm
Decision Phase
Dose Adjustment Phase
Stable Phase
Evaluative Phase
Adopted from Ballantyne JC, Mao J. N England J Med 2003;349:1943-53
Opioid Therapy for Non-cancer
Pain
Features of Noncompliance
Adopted from Ballantyne JC, Mao J. N England J Med 2003;349:1943-53
Adjuvant Medication
• Adjuvants may or may not elicit pain
relief.
• The nature of the dose/response
relationship is not predictable.
• They are mainly useful in Neuropathic
pain.
Adjuvant Medication
•
•
•
•
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•
•
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Antidepressants.
Anticonvulsants.
Neuroleptic agents.
Antiarrythmic drugs.
Corticosteroids.
Osteoclast inhibiting medications.
Spasmolytics.
Alpha blockers.
Alpha 2 agonists.
Antidepressants for Chronic Pain
• Antidepressants increase the extraneuronal
concentrations of Norepinephrine and
Serotonin, which are responsible for modulating
pain.
• The neurotransmitter Serotonin is released by a
major descending inhibitory pathway that arises
in the Periaqueductal gray region of the
midbrain.The Noradrenergic pathway is a major
descending pathway.It arises in the Locus
Ceruleus of the pons.
Antidepressants with NE &
5HT Activity
• TCAs (NE > 5HT) • SNRIs (? NE = 5HT)
–
–
–
–
amitriptyline
imipramine
desipramine
nortriptyline
• SSRIs (5HT > NE)
– Citalopram and escitalopram
– paroxetine
– fluoxetine
– sertraline
– buproprion
• dopaminergic
– venlafaxine
• dopaminergic
– mirtazapine
• Alpha-adrenergic
– fluvoxamine
– duloxetine
Anticonvulsants
• Sodium Channel Antagonists
– carbamazepine, lamotrigine, oxcarbazepine,
phenytoin, topiramate, zonisamide
• Calcium Channel Antagonists
– ethosuximide, gabapentin, lamotrigine, topiramate,
valproate, zonisamide, pregabalin
• GABA modulation
– gabapentin, phenobarbital, tiagabine, topiramate,
valproate, zonisamide
• Glutamate antagonists
– topiramate, felbamate
Evidenced-Based Medicine
Antidepressant
NNT
TCA (balanced)
2.7
TCA (selective noradrenergic)
2.5
SSRI
6.7
Anticonvulsants (Na)
2.5
Anticonvulsants (Ca)
4.1
Sindrup. Neurology 2000;55:915-921.
Physical Therapies
Goals of Rehabilitation
• Establish an accurate diagnosis
• Minimize deleterious local effects of acute injury
through modalities and medications
• Allow proper healing
• Maintain fitness through exercise
• Return to normal function through recovery and
maintenance techniques
Psychological Treatment
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Cognitive Behavioral Therapy
Relaxation techniques
Biofeedback training
Behavioral Therapy
Group Therapy
Interventional Therapies
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Nerve blocks and Joint injections
Epidural steroid and Transforamenal injections
Facet injections and Radiofrequency lesioning
Discography and IDET
Vertebroplasty
Sympathetic Plexus Block (Stellate, Celiac, Lumbar,
Hypogastric, and Impar)
Botulinum toxin
Epidural neuroplasty
Spinal cord stimulation and Intrathecal pumps
Minimally invasive corrective spine procedures
Summary
• Comprehensive Evaluation
– Type of Pain
– Treatment Endpoint and Goals of Therapy
– Screening for Risk of Aberrant Behavior
• Multidisciplinary Management
– Sequence of various approaches is different
than for Acute or Cancer Pain
• Opioids are not the first line therapy
Summary
• Primum non nocere