New Concepts in
Pain Management
Melanie Christina, M.D.
Presbyterian Hospital Dallas
Medical Director, Heartland Hospice
Definition:
Pain
An unpleasant sensory and emotional
experience associated with actual or
potential tissue damage, or described in
terms of such damage
 Pain is subjective. There is no
neurophysiological or chemical test that
can measure pain.

INTERNATIONAL ASSOCIATION
FOR THE STUDY OF PAIN
Prevalence of Pain
Over 30 million Americans suffer from
chronic nonmalignant pain
 20-30% of the American public suffer
from acute or chronic pain
 Over 70% of patients with advanced
cancer report having moderate to
severe pain

Barriers in the treatment of
Pain
Inadequate assessment
 Specific populations more likely not to be
treated
 Patient’s reluctance to report pain
 Patient’s reluctance to take opioids
 Doctor’s reluctance to prescribe opioids

– Fear of regulatory scrutiny
– Fear of causing addiction
– Lack of knowledge regarding dosing and side effects

Important concepts to
Understand
Addiction
– Psychological dependence on substances for their psychic effects and
is characterized by compulsive use despite harm.

Analgesic Tolerance
– The need to increase the dose of opioid to achieve the same level of
analgesia.

Physical Dependence
– A physiologic state of neuroadaptation which is characterized by the
emergence of a withdrawal syndrome if drug use is stopped or
decreased abruptly, or if an antagonist is administered.

Pseudoaddiction
– Pattern of drug-seeking behavior of pain patients who are receiving
inadequate pain medication. Behavior is mistaken for addiction.
Guidelines for the management
and treatment of Pain
 WHO
- global initiative on pain
management (1986)
 Texas State Board of Medical
Examiners (1993)
 Federation of State Boards (1998)
 JCAHO (1999)
 Governmental guidelines (AHCPR)
 American Pain Society
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and many more!!!!!!
Texas State Board of Medical
Examiners’ Position
 “Quality medical practice dictates that those
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citizens of TX who suffer pain and other
distressing symptoms should be adequately
relieved so that their quality of life is as
optimum as can be.”
“The TSBME recognizes that opioids and
other Scheduled Controlled substances, are
indispensable for the treatment of pain…”
“It is the position of the board that these
drugs be prescribed for the treatment of
these symptoms in appropriate and adequate
doses…”
Texas State Board of Medical
Examiners’ Position
 “The Board recognizes that pain, and many


other symptoms are subjective complaints
and appropriateness and adequacy of drug
and dose will vary from individual to
individual.”
“The standard will be determined largely by
treatment outcome…”
Physicians should be diligent in preventing
(controlled substances) from being diverted
from legitimate to illegitimate use.
Standards used by Board when evaluating
use of Controlled substances:

DOCUMENTATION-Medical records should include:
– medical history and physical
– diagnostic, therapeutic and laboratory results
– evaluations and consultations
– treatment objectives
– discussion of risks and benefits
– treatments
– medication (date, type, dosage, quantity)
– instructions and agreements
– periodic review
Joint Commission Standards
on Pain Management

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Patient’s have a right to appropriate
assessment and management of pain
Pain needs to be assessed, documented and
followed for appropriate interventions
Policies and procedures should support the
appropriate use of pain medications
Patients and their families should be educated
on pain management
Discharge planning should include symptom
management
Governmental Guidelines
www.guidelines.gov
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1995 - “Clinical practice guidelines for chronic
non-malignant pain syndrome”
1998 - “The management of persistent pain
in older persons”
1999 - “Procedure guideline for bone
treatment pain”
2000 - “Control of pain in patients with
cancer. A national clinical guideline”
2002 - “Clinical practice guideline for the
diagnosis, treatment and management of
reflex sympathetic dystrophy/complex
regional pain syndrome”
Current Legal Climate Undertreatment of Pain
Landmark case in California with a
family suing the doctor for inadequate
pain control in their dying, 85 year old
father during the last week of his life.
Jury trial awarded family 1.5 million
claiming the physicians lack of attention
to pain was “reckless negligence” and
constituted elder abuse.
Tips for Physicians to protect
themselves from charges of
Undertreatment of pain:
Review your practice against JCAHO
standards
 Improve knowledge in pain assessment and
treatment
 Utilize local consultation resources
 Improve knowledge and skills in assessing
substance abuse; utilize local resources for
substance abuse referrals and treatment

TYPES OF PAIN
Pathophysiologic categorization

NOCICEPTIVE
– SOMATIC
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Stimulation of the
somatic nervous
system
skin, soft tissue,
muscle, bone
easily localized
– VISCERAL
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stimulation of the
autonomic nervous
system
GI and GU tracts,
cardiac, lung
difficult to describe
and localize

NEUROPATHIC
– PERIPHERAL
PROCESSES
(neuroma)
– CNS PROCESSES
(phantom pain)
– COMPLEX REGIONAL
PAIN
Classification of Pain
Based on clinical course
Acute
pain
Chronic pain (non-cancer)
Cancer pain
Post-surgical pain
Assessment of Pain
“ABCDE” Mnemonic
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Ask about pain regularly; Assess pain
systematically
Believe the patient and family in their reports of
pain and what relieves it
Choose pain control options appropriate for the
patient, family and setting
Deliver interventions in a timely, logical and
coordinated fashion
Empower patients and their families; Enable
them to control their course to the greatest
AHCPR 1994
extent possible
Describing Pain:
“PQRST” Mnemonic
 Provoking
or Palliative factors
 Quality of pain
 Radiation
 Severity
 Temporal
Goals in the treatment of
pain
 Improve
quality of life
 Encourage mobility
 Reduce hospitalizations and ER
admissions
 Improve job performance
 Impact function in a family unit
 Prevent depression/suicide
Step 3, Severe Pain
Morphine
Hydromorphone
Methadone
Fentanyl
Oxycodone
+ Nonopioid analgesics
+ Adjuvants
WHO 3-STEP
LADDER
Step 2, Moderate Pain
Combination opioids
Tramadol
+ Adjuvants
Step 1, Mild Pain
Aspirin
Acetaminophen
Nonsteroidal anti-inflammatory drugs
+ Adjuvants
Utilization of Opioids:
Chronic Pain
Dose around the clock - achieve blood
levels in the therapeutic range and
avoid blood levels falling below pain
threshold
 Rescue dosing - 10% of total 24 hour
dose
 Dose titration:

– mild pain: increase dose by 10%
– moderate pain: increase dose by 25-50%
– severe pain: increase dose by 100%
Routes of Administration
Oral - preferred
 Buccal/sublingual
 Rectal
 Transdermal
 Subcutaneous
 Intravenous
 Intramuscular - CONTRAINDICATED
 Intrathecal

Equianalgesic Conversion Table
ANALGESIC
ORAL DOSE
PARENTERAL DURATION
DOSE
OF ACTION
(HOURS)
HALF-LIFE
(HOURS)
ORAL:
PO
PARENTERAL MORPHINE
RATIO
:ANALGESIC
RATIO
Morphine
30mg
10mg
4-6hr
2-4hr
3:1
Oxycodone
20mg
3-5hr
4-5hr
Hydromorphone
7.5mg 1.5mg 3-4hr
2-3hr
5:1
4:1
Methadone
20mg
15-50h 2:1
3:1
Codeine
200mg 130mg 4-6hr
3hr
1:7
Hydrocodone
30mg
3-6 hr 3-4hr
Meperidine
300mg 75mg
2-4hr
10mg
4-6hr
2-3hr
1:1
1.5:1
1.5:1
1:1
4:1
1:10
Variables in Considering
Equianalgesic Doses
Pain intensity
 Prior opioid exposure
 Incomplete cross tolerance
 Age of Patient
 Route of administration
 Level of Consciousness
 Preexisting conditions

Common Side Effects and
treatments
Constipation - All patients on opioids need
a regular bowel program.
 Nausea - quickly develop tolerance to this
 Pruritus - may need to switch opioids
 Sedation - if tolerance doesn’t occur can
use stimulants
 Respiratory depression - most feared yet
rare side effect if proper dosing followed

Fear of Respiratory Depression
from Opioid Use
Patients develop tolerance to the respiratory
depressant effects early in course of therapy
 Patients with COPD have been shown to
experience improvement in exercise
tolerance and decreased SOB
 Terminally ill patients required 1.5-2.5 times
their regular dose of analgesia to control
breathlessness; without effect on O2
saturation or respiratory rate

Annals Internal Medicine 119: 906, 1993
Fentanyl Transdermal System
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Medication is absorbed into the subcutaneous tissue;
then absorbed into systemic circulation via capillaries
May take 18-24 hours before effect of medication
therefore not idea for acute pain management
Continue previous medicine for 18-24hr after placing
the patch
Use short-acting opioid for rescue dosing
Adjust dose no sooner than every 6 days
Once removing patch the effect may persist for up to
24 hours
Duragesic: Oral Morphine
Equianalgesic Table
Morphine dose in
24hr
Duragesic Patch
Strenth
90mg (range 45-134mg)
25ug/hr
180 (range 135-224mg)
50ug/hr
270 (range 225-314mg)
75ug/hr
360 (range 315-404mg)
100ug/hr
For each additional 90mg
(range 45-134mg)
Add 25ug/hr
GOOD RULE OF THUMB: 2 X
DURAGESIC DOSE = 24 HOUR
Steps in Changing Opioids
Calculate 24 hour dose of current opioids
 Use equianalgesic table - convert dose of
current drugs to equivalent new drug
 Adjust the dose of new drug to
accommodate patient variability and
incomplete cross tolerance
 Determine dosing intervals according to
duration of action of new opioid
 Calculate rescue dose

Example: Mr. Kaye is receiving 8mg Dilaudid po q
3h, and his physician would like to change the
patient to a sustained release morphine product for
patient convenience.
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Calculate the 24 hour dose of Dilaudid
– 8mg x 8 = 64mg Dilaudid
Using the morphine:Dilaudid ratio figure the 24 hour
equianalgesic dose morphine
– Morphine: Dilaudid (4:1)
– Multiply 64 by 4 = 256mg morphine equivalent
Divide the 24 hour dose by 12 for the long-acting
morphine dose
– 256 divided by 2 = 128 or rounded up to MS
Contin 130mg q 12hour
On the same patient, figure what the
rescue dose of short-acting morphine
would be?

Figure the total 24 hour dose of routine
medication being given
– 260mg morphine per day

10% of that can be given every 1-2
hours as needed for breakthrough pain
– 10% of 260 = 26mg
– can give morphine immediate release
tablets (30mg) q 1-2 h or morphine liquid
(20mg/ml) 1.25 ml q 1-2 hour
On the same patient, if he were to
stop swallowing what could be done?
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Switch to IV therapy
– Figure the total dose of morphine given (260mg)
– Use the equianalgesic chart to figure
oral:parenteral ratio (3:1)
– Divide 260mg by 3 = 87mg IV morphine/day
– Decide the route (subcutaneous or IV)
– Divide 87mg/24hour = 3.6mg/hour
– Have boluses of 25-50% total hourly dose
available q 15-30mins (1-2mg)
Use MS Contin rectally at the same dose and give the
rescue dose as a sublingual medication
Use sublingual medication on a q 4 hour schedule
On the same patient, if Mr. Kaye stopped
swallowing tablets but had an extended
prognosis?

Consider switching to Duragesic Patch
– Total Morphine dose 260mg
– Duragesic patch dose (per table) is 75ug/h
– Via 2x rule: 260/2=130 or 125ug/h
– Same breakthrough medication is
appropriate

Stop the previous routine medication
18-24 hours after the patch is placed
Bone Pain from Metastasis
 NSAID
 Steroids
 Bisphosphonates
 Radiopharmaceuticals
 Radiation
Therapy
Neuropathic pain
Definition: Arising directly from central
and peripheral damage by injury,
disease or medical treatment. A
pathological pain that serves no
adaptive purpose.
 Frequently becomes chronic and may
escalate over time
 Challenging to diagnose and treat

Afferent Pain
Pathways
Termination in THALAMUS
with afferent fibers
projecting rostrally to
the somatosensory
CORTEX and LIMBIC
SYSTEM
Nociceptive signals ascend
in the ANTEROLATERAL
WHITE MATTER
Nociceptors terminate in the
DORSAL HORN and
synapse in the Rexed Laminae
SPINOTHALAMIC TRACTS
send transmission rostrally after
decussating in spinal cord
NOCICEPTORS react to noxious
stimuli (heat, chemical, mechanical)
A-delta fibers
C fibers
Mechanism and Mediators of
Pain
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Painful stimuli causes depolarization of A-DELTA
(thinly myelinated) and C-FIBER (unmyelinated)
Inflammation from chemical messengers released
from damaged tissue (AMP, Protein), mast cells
(Prostaglandin), macrophages (cytokines)
This leads to lowering of activation threshold and
ectopic discharges = Peripheral sensitization
Neuron itself releases substance P which turns on
messengers of immune cells
Positive feedback loop
Increase input into Dorsal Horn
Peripheral Sensitization
Lowering of the nociceptor
depolarization threshold and increase in
ectopic discharges
 Due to altered expression and
distribution of sodium channels at the
level of injured nociceptor and Dorsal
Root Ganglion

Mechanisms of Pain
in the Dorsal Horn
Depolarized Nociceptors release Glutamate
at the terminal end
 Glutamate normally binds to AMPA receptor
causing depolarization of DH cells
 With peripheral sensitization and increase
input, the NMDA receptor becomes exposed
and Glutamate binds NMDA and AMPA.
(wind-up)
 This sensitizes central nervous system such
that subthreshold input depolarize neurons

Central Sensitization
Lowering of the threshold of spinal horn
neurons, with an increase magnitude
and duration of response to stimulation
 Expansion in size of receptive field
 Release of tachykinins (substance P and
neurokinin A)

– These bind to neurokinin receptor and
increase intracellular calcium
– Increases NMDA receptor up regulation
– Increase in Nitrous oxide synthetase
Importance of NMDA
Receptor
The NMDA Receptor is involved in the
propagation of neuropathic pain
 Tolerance is also related to this receptor
 When the NMDA Receptor is activated,
there is Central Sensitization
 The opioid receptor, mu receptor, is less
responsive to opioids

NEUROPATHIC PAIN
Nerve Blocks
Local Anesthetics
Surgical Management
Decompression
Medical
Management
Membrane stabilizing
Agents
STEROIDS
Drugs that enhance
dorsal horn inhibition
GABA-B
agonists
Baclofen
ANTIARRHYTHMICS
Lidocaine
Mexilitine
ANTIEPILEPTICS
Oxcarbazepine
Clonazepam
Gabapentin
NMDA Receptor
Antagonist
ANTIEPILEPTICS
Carbamazepine
Oxcarbazepine
Phenytoin
Valproate
Ketamine
Dextromethoraphan
Methadone
Amantadine
ANTIDEPRESSANTS
Amitriptyline
Desipramine
Imipramine
Nortriptyline
Most commonly used
adjunctive treatments
 Amitryptilline
 Carbamazepine
 Gabapentin
 Corticosteroids
Methadone
A
Mu agonist and noncompetitive
NMDA receptor antagonist
 No neuroactive metabolites
 Elimination is independent of renal
function
 Less constipating
 Good oral bioavailability
 Extremely low cost
Conversion to
Methadone
Daily oral morphine dose
equivalents
< 100mg
Conversion ratio of oral
morphine to methadone
3:1 (ie. 3mg morphine:1mg
methadone)
101-300mg
5:1
301-600mg
10:1
601-800mg
12:1
801-1000mg
15:1
> 1000mg
20:1
Interesting Case: 65yr old
Anesthesiologist with Diabetic
Peripheral neuropathy
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Mr. C. has stocking-glove distribution
neuropathy. He had excruciating pain (10/10)
while on Norco (10/325mg) 6-8 per day.
Neurontin was not well tolerated
Elavil was contraindicated due to cardiac
history and conduction system disorder
Mr. C. was depressed and didn’t think life was
worth living with this pain
Neuropathic pain due to
Diabetes
After discussion with patient and family,
we initiated a course of Methadone
 His current dose of Hydrocodone was
60-80mg daily or the equivalent of 6080mg morphine
 My conversion with Methadone at low
dose morphine is 5:1
 I started Mr. C on Methadone 5 mg q 8
ATC with 2.5mg q 3 hours prn

Methadone for neuropathic
pain
Patient tolerated Methadone well
 Within 24 hours his 10/10 pain was
rated at 3/10
 Within 1 week, his pain was gone
(0/10);
 Precaution using Methadone: Slow
accumulation, varied half-life, needs to
be adjusted upward slowly (about q 7
days)
