National Overdose Deaths—Number of Deaths from Benzodiazepines. The figure above is a bar chart showing the total number of US overdose deaths involving benzodiazepines from 2001 to 2013. The chart is overlayed by a line graph showing the number of deaths by females and males. From 2001 to 2013 there was a 4-fold increase in the total number of deaths.
National Overdose Deaths—Number of Deaths from Rx Opioid Pain Relievers. The figure above is a bar chart showing the total number of US overdose deaths involving opioid pain relievers from 2001 to 2013. The chart is overlayed by a line graph showing the number of deaths by females and males. From 2001 to 2013 there was a 3-fold increase in the total number of deaths.
National Overdose Deaths—Number of Deaths from Prescription Drugs. The figure above is a bar chart showing the total number of US overdose deaths involving opioid prescription drugs from 2001 to 2013. The chart is overlayed by a line graph showing the number of deaths by females and males. From 2001 to 2013 there was a 2.5-fold increase in the total number of deaths.
2015: Pain Management - A Practical and Functional Approach-Lakkaraju
Ravi Lakkaraju, MD
Poway Spine and Pain
The International Association for the Study of
Pain (IASP) defines pain as “an unpleasant
sensory and emotional experience associated
with actual or potential tissue damage”
Pain is the single most common reason for
patients to seek medical attention
2000 – 13.1% of population over 65
2030 – 20% of population over 65
25-50% of community elders suffer chronic
pain of some kind
45-50% of Nursing home residents suffer
Chronic pain effects approx. 100 million
Roughly cost $635 billions annually
Incidence greater than Diabetes, heart disease
and cancer combined.
- sensitization of nociceptors
- Nerve damage
- Release of sensitizing humoral mediators
In some conditions, nociception due to tissue
damage may occur, but the patient may not
perceive, or feel it
i.e., diabetic peripheral neuropathy
Conversely, the patient may perceive severe
pain with no demonstrable evidence of tissue
i.e., trigeminal neuralgia
The process by which afferent nerve endings
participate in translating noxious stimuli (e.g.,
a pinprick) into nociceptive impulses
Noxious stimulation is first carried by the
faster A-delta fibers and then by the slower C
Local injury can cause nociceptors to become
hypersensitive to noxious stimuli, thereby
creating a condition called sensitization
• The process by which impulses are
sent to the dorsal horn of the spinal
cord and the brain
• Noxious stimulation is first carried
by the faster A-delta fibers and then
by the slower C fibers
• The process of dampening or amplifying pain-
related neural signals
• A variety of modalities can modulate these
• Systemic or neuro-axial injection of opioids
• Electric stimulation, TENS, Acupuncture, Massage.
• TCA’S, AED’s
• Stress, Anxiety
Refers to the subjective experience of pain
Results from the interaction of transduction,
Dependent on the psychological aspects of the
Neuropathic pain is pain due to damaged or
The pathophysiology of neuropathic pain can have
both peripheral and central mechanisms
it is doubtful that a single mechanism can account
for all cases
The end result is pain that is experienced without
evidence of noxious stimulus
- Enhanced pain intensity
- Enlargement of pain areas
- Widespread hyperalgesia
- Enhanced disability
- sensitization of central neural structures
- Dysfunction of endogenous pain modulation
- Psychophysical Assessments
- Objective Assessments
- Measuring spread of pain and referred pain
- Measurement of endogenous modulation
- Measurement of Temporal Summation
Can be classified mostly into 3 broad groups:
- Curative/Disease modifying
Simplest and preferred when the identifiable
pathophysiological process is present and
becomes the target of treatment.
Typically pain should resolve once the
underlying process resolves
Examples – ORIF, Appendectomy, Angioplasty
Difficult to treat ‘upstream’ pathophysiologic
Appropriate when 2 conditions apply
- the curative model is not appropriate
- major goal of treatment is improving patient’s
ability to function
- Examples – multidisciplinary pain rehabilitation
(PT, OT, counselling, biofeedback, CAM,
vocational rehab, etc.,)
Combination of Medication management to
Less demanding rehabilitative therapies
Low levels of pain can cause high functional
Although pain threshold increases with age,
tolerance for pain decreases.
Multiple pain complaints, multiple medical
problems, poor communication/under-
Cognitive decline, depression, anxiety,
Poor nutrition, poor tolerance to tests and
Can be more reliable than just pain reporting,
especially in low cognitive patients.
Changes in interpersonal interactions
Changes in activity patterns or routine
Mental status changes
Decreased renal function (decrease in
glomeruli, decrease in renal excretion, low
GFR, higher serum drug levels)
Decreased hepatic function (decreased
Cyt.P450 oxidation causing higher serum drug
Decreased serum protein, decreased functional
binding to proteins – Less unbound drug,
increased CNS effect.
Two metabolites – M3G, M6G (6 is more active
and leads to sedation, as this is renally
Elimination by hepatic metabolism to
T1/2 is 2-4 hrs. may be elevated in elderly up
to 15 hrs.
Metabolized to normeperidine
Not reversible by naloxone
This leads to respiratory depression and
excitatory neurotoxicity, anti-cholinergic
effects, urinary retention
Blocks reuptake of NE and HT, can cause fatal
reaction with concomitant SSRI (Fluoxetine)
Decreased nerve conduction velocity (loss of
myelin on axons, decrease axonal synapses)
Elderly adults rely on C-fiber input when
reporting pain ; whereas, younger patients use
C and A-delta.
TENS, heat, acupuncture, relaxation
Exercise – targeted therapies with realistic
achievable goals, should be integrated into
daily routine and ADL’s, progress slowly as
function and strength improve.
PT / OT , custom adaptive equipment as
needed to decrease pain and improve function.
NSAIDS – exercise caution due to renal, GI and
Anti-depressants and Anti-convulsants -
adjunctive role in chronic pain especially
neuropathic pain states. Dosing limited by side
Topical anesthetic / NSAID patches – limited
penetration into the tissues, effective only at
Equalizing the ‘Pain Pendulum’
‘Balance’ pain relief with risks associated with
(Not too much…not too little…just enough !!)
Always administer tools for risk assessment
(COMM, DIRE, ORT, SOAPP, SOAPP-R)
Have a clear written agreements / documentation
/ ‘opioid contract’
All opioid contracts should be simple and written
at ‘6th or 7th’ grade level or even lower !
Written consent from patient that ‘contract’ was
read and clearly understood by the patient.
Opioid contract/Agreement sets precedence to
‘Rules/responsibilities on patients and reviews
risks involved. Not a binding agreement but a
good practice for every provider.
Templates of medication agreements can be downloaded from www.SanDiego-
Create function based treatment plans with
goals, e.g, begin PT, document improvement in
ADL’s and daily routine. Review partner or
care-giver input apart from patients self report.
Review therapy notes.
Must have a good collaboration between
patient and clinician
Apart from pain scores, goals should be
realistic, meaningful and verifiable.
Treatment plan should be periodically re-
assessed, modified based on goals and
Always have a ‘Exit strategy’ or plan
termination that is mutually agreed upon by
works on 3 receptors- mu, kappa, delta.
Exerts 3 actions – 1.inhibits transmission of
nociceptive input from the periphery to the
spinal cord, 2.activation of descending
inhibitory pathways that modulate
transmission in the spinal cord (pain
“dampening”), 3. Alteration of limbic system
Thus, opioids modify sensory and affective
aspects of pain.
Start at lowest possible dose for opioid –naïve
patients – ‘start low go slow’
Opioid tolerant patients – select dose and
medication on case by case basis. When
converting from other opioid start at 50%
equianalgesic dose and titrate per response.
May use ER/LA therapy alone, SA only, or a
combination of ER/LA with a SA opioid.
Recommend not to use more than one SA
SA opioids typically have rapid onset (10-60 min)
and relatively short duration (2-4 hrs)
ER/LA opioids have relatively slow onset
(between 30 to 90 min) and relatively long
duration of action (4 to 72 hrs)
Combination with non-opioid adjunctives can be
beneficial and can have opioid sparing effects. But
monitor for non-opioid drug toxicity.
No ‘ceiling’ effect for opioid analgesic dosing.
Selecting ‘Abuse-Deterrent’ formulations may
minimize the opioid abuse.
Morphine dose is used as a ‘standard’ for dose
comparison of other opioids. Morphine
equivalent daily dose (MEDD)
Recommend not to exceed >100 mg/day
exercise caution with morphine and Demerol
use in renal insufficiency patients. Most other
opioids eliminated by hepatic metabolism.
Codeine is a prodrug and not all patients
convert it to an active form.
When treating chronic pain with opioids, also
be prepared to proactively treat side effects.
Common side effects include respiratory
depression, sedation, mental clouding or
confusion, nausea, vomiting, constipation,
pruritus and urinary retention.
Side effects tend to subside with time with the
“exception” of Constipation.
Periodic urine drug screens (should be performed
for the duration of COT)
244 un-intentional Rx drug related deaths in San Diego county in 2014, 5723 ER
discharges related to pain killers in 2013
Utilizing ‘CURES’/PDMP system for monitoring
and surveillance (CONTROLLED SUBSTANCE UTILIZATION REVIEW AND
EVALUATION SYSTEM). Register by Jan 1st, 2016.
Can complete registration online at https://pmp.doj.ca.gov/pmpreg
Perform Pill counts at each visit, especially in high
July 2012, FDA released ‘final’ guidelines to
REMS for ER/LA formulations.
2014-2015 – Government move to initiate an
action plan to formulate ‘National Pain
Urine drug screens typically done every 1-3
More frequently done in high risk patients, e.g,
Prior history of addiction, past abuse, aberrant behavior, occupations demanding
mental acuity, elderly, unstable or dysfunctional social environment, comorbid
psychiatric or medical conditions
Sometimes daily or weekly monitoring may be necessary for patients at very high
risk of adverse outcomes.
Urine specimens can be adulterated and should be aware.
Oral swab tests more easy to administer and can be more valuable than urine drug
Screen for hypogonadism in patients on COT,
especially with signs and symptoms of fatigue, mood changes, decreased libido,
loss of muscle mass and osteoporosis.
Perform opioid rotation if lack of efficacy, side-
effects of one opioid class, altered pharmaco-
kinetics, changes in absorption.
CHRONIC PAIN PATIENT ADDICTED PATIENT
Medication use is not out of control
Medication use improves quality of life
Wants to decrease medication if adverse effects
Is concerned about the physical problem being
treated with the drug
Follows the practitioner-patient agreement for
use of the opioid.
May have left over medication
medication use is out of control
Medication use impairs quality of life
Medication use continues or increases despite
Unaware of or in denial about any problems that
develop as a result of drug treatment
Does not follow opioid agreement
Does not have left over medication. Loses
prescriptions. Always has a story about why
more drug is needed.
Tolerance – decreased efficacy over time
Dependence – tolerance +withdrawal
Addiction – ‘neurobiological disease’. Strong
genetic influence. Preoccupied with continued
use despite harm
Pseudoaddiction – happens when pain is
undertreated. “drug seeking” or “clock
watching”. Usually resolves with effective pain
Total Female Male
Source: National Center for Health Statistics, CDC Wonder
18,000 Total Female Male
Source: National Center for Health Statistics, CDC Wonder
Total Female Male
Source: National Center for Health Statistics, CDC Wonder
Reasons to terminate may include (healing or recovery
from the treatment condition, intolerable side-effects, lack of response, discovery of
abuse or misuse or addiction)
Typically 10% dose reduction per week. Slower
taper will minimize unpleasant withdrawal
Clonidine can be used. 0.1 – 0.2mg PO every 6
hrs daily or patch at 0.1mg/24 hours.
Drug rehab - Methadone
Respiratory depression usually preceded by
warning signs and can be prevented with
Take home Naloxone Rx for patients with high
risk for overdose
. In 2014 FDA approved hand held auto-
injector (Evzio) and can be used at home by
family members or caregivers.
Mu-1 agonist and NMDA antagonist
Analgesic duration of 4-6 hrs
Elimination t1/2 15-60 hrs
Can cause QT prolongation, Torsade de pointes
Has been long used to treat addiction.
Long plasma elimination half life, relatively
short analgesic half life makes it optimal for
Has opioid and non-opioid receptor effects
causing varied effects – ‘Broad spectrum
Metabolized by liver enzymes that differ from
those associated with most other opioids,
leading to drug-drug interactions.
Significant genetic variations in the liver
enzymes that metabolize methadone
Metabolism effected by cigarette smoking and
Lowest possible dose titration should be
followed even for opioid tolerant patients.
1 provider and 1 pharmacy for all controlled
Use medication agreements when prescribing
Don’t mix opioids and CNS
depressants/sedatives. Monitor polypharmacy
Implement multidisciplinary approach to treat