This presentation details how to conduct a comprehensive pain assessment, considerations when prescribing analgesics, and when opioids may be appropriate.

1. Pain Management in the Context of an Opioid Epidemic:
Considerations and Tools for Success

2. CME Provider Information
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Physicians
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Statement – Amedco LLC designates this live activity for a maximum of 1 AMA PRA Category 1 CreditTM.
Physicians should claim only the credit commensurate with the extent of their participation in the activity.

3. Objectives
• Incorporate a comprehensive pain assessment
• Describe four different types of pain
• Appreciate pain physiology and how it relates to pain management
• Identify non-opioid treatments as part of a comprehensive plan
• Detail three tools to incorporate to help manage patients on opioids

4. Reductions in Prescribed Opioids Has Not Led
to Reductions in Opioid-related Deaths
*Provisional data for the 12-month period Jan. 2020–Jan. 2021 https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm
2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020
Overdose deaths: 94,134* Opioid prescriptions 143,390,9511 (44.4% decrease since 2011)
1

5. Opioid Deaths by Opioid Type
https://www.cdc.gov/nchs/images/databriefs/401-450/db428-fig4.png, https://www.cdc.gov/nchs/products/databriefs/db428.htm
Heroin Fentanyl

6. Benefits and Risks Associated With Opioids
Benefits
• Analgesia
• Option for patients with
contraindications for
non-opioid analgesics
• Relieves suffering
• May improve function and
quality of life
Risks
• Life-threatening respiratory
depression/overdose
• Development of SUD/OUD
• Diversion
• Inadvertent exposure to
family and pets
• Interactions with other
meds and substances
• Neonatal abstinence syndrome
• Physiologic dependence and withdrawal

7. Terminology
Misuse Use of a medication in a way other than how it is prescribed.
Abuse Use of a substance with the intent of getting high.
Tolerance Increased dosage needed to produce a specific effect.
Dependence State in which an organism only functions normally in the presence of a substance.
Diversion
Transfer of a legally controlled substance, prescribed to one person, to another
person for illicit (forbidden by law) use.
Common Term Preferred Term
Addiction Substance Use Disorder
Drug Seeking, Aberrant, Problematic Behavior Using Medication Not as Prescribed
Addict Person With Substance Use Disorder (SUD)

8. Important Considerations
• Pain is often multifactorial and
uniquely impacts individuals, and
benefits from non-pharmacologic and
pharmacologic approach
• Establishing a positive patient-
physician partnership provides
an important foundation that will
optimize treatment outcomes
– Develop a mutual understanding
of treatment goals/expectations
– Build rapport and trust
– Encourage patients take on an
active role in managing their pain
• Substantial improvement in function and
quality of life can be anticipated even
if pain is not eliminated
• Persistent pain is treatable, but it
is not curable

9. Multifaceted Pain Assessment
Self and Proxy Report
• NRS
• VDS
• FPS
Potential Contributors
• History – medical, psychological
social, spiritual, and family
• Physical exam
Behavior Assessment
• Direct observation
• At rest and with activity
Analgesic Trial

10. Acute or Chronic Pain
Acute
• Acute and duration of
< 1 month
• Sudden onset, self-limiting
• Ideally resolves
with healing
• Triggered by tissue
damage and inflammation
• Has protective value
• Inflammatory mediation
• Subacute, pain that
continues for 1-3 months,
can become chronic
“An unpleasant sensory and
emotional experience associated
with, or resembling that associated
with, actual or potential
tissue damage.”
—IASP (July 2020)
Chronic
• Lasting 3 months
or longer
• Generally steady-
state or worsening
• Persists beyond
normal healing period
• Serves no value
• Peripheral and
central sensitization

11. Pain Assessment: Self-report
Heapy A, Kerns RD. Psychological and behavioral assessment. In: Raj's Practical Management of Pain. 4th ed. 2008:279-295; Zacharoff KL, et al.
Managing Chronic Pain with Opioids in Primary Care. 2nd ed. Newton, MA: Inflexion, Inc.; 2010.
• Description of pain
PQRST= Palliative/Provocative Factors, Quality/Quantity, Region/Radiation,
Severity, Temporal factors
• What relieves the pain?
• What causes or increases
the pain
Location Intensity Onset duration Variations/
patterns/rhythms
Quality
• Effects of pain on physical, emotional,
and psychosocial function?
• Patient’s current level of
pain and function

12. Pain Intensity and Functional Interference
Cleeland C and Wang S (1999) Oncology NCCN Proceedings
• As pain intensity increases, so does
the degree of functional interference
• The figure on the right shows
the relationship in persons with
cancer pain
• Studies of patients with AIDS and
chronic non-cancer pain show
similar interferences with function
with increasing pain
As pain intensity increases,
so does the degree of functional interference
relate
walk
sleep
active
mood
work
enjoy
walk
sleep
active
mood
work
enjoy
sleep
active
mood
work
enjoy
sleep
active
mood
work
enjoy
work
enjoy
enjoy
3 4 5 6 7 8
Worst Pain (0-10 scale)

13. Proxy Pain Report
• Healthcare Professionals
– Physicians
– APPs
– Nurses
– Nursing assistants
• Families

14. Potential Contributors and Treatment
• Conditions with focus on those
attributable to pain
– Medical: osteoarthritis, gout,
spinal stenosis, post-herpetic
neuralgia, cancer, etc.
– Post-surgical: hip fracture with
repair, joint replacement,
other surgeries
• Conditions that may impact metabolism
or ability to tolerate analgesics
– Liver, renal, pulmonary, cognitive,
gastrointestinal (nausea and constipation)
• Identify previous treatments, including
effectiveness and adverse effects
– Query the state Prescription Drug
Monitoring Program (PDMP)
– Corroborate patient/family report
– Past medical records as appropriate
• Assess barriers, such as the cost of
treatment, childcare, transportation,
attitudes, and health-care literacy

15. Prescription Drug Monitoring Program
• Reports on scheduled drugs
including opioids that are filled
• Nearly all available 24/7/365
with 54 operational within
the US
– No national DPMP exists
• Requirements mandating
use vary by state
– Know your state law
• Multiple benefits have been reported
– Lower rates of opioid-prescription
ED visits and hospitalizations
– Reduction in high-dose
prescriptions and over-prescribing
– Reduction in doctor shopping
• Identify drugs that increase overdose
risk when taken together (such as
benzodiazepines, gabapentinoids,
opioids, and other sedatives)

16. Psychological, Social, and Family History
• Social history
– Employment, cultural background,
social network, relationship
history, legal history, and other
behavioral patterns
• Psychological history
– Mental health diagnoses,
depression, anxiety,
OCD, and PTSD
– Alcohol, tobacco, THC, and
recreational drug use
• History of adverse childhood
experiences (ACES)
• Family history of substance use
disorder and/or psychiatric disorder
Depression and anxiety can be
predictors of chronic pain.

17. Behavioral Assessment: Non-verbal Pain Indicators
Changes in interpersonal interactions
• Combative, disruptive, resisting
care, decreased social
interactions, withdrawn
Changes in mental status
• Confusion, irritability,
agitation, crying
Changes in usual activity
• Refusing food/appetite change,
increased wandering, change
in sleep habits
Facial expressions
• Grimacing, slight frown,
rapid blinking, sad/frightened,
any distortion
Vocalizations (crying,
moaning, groaning)
• Crying, moaning, groaning,
grunting, calling out, noisy
breathing, a5ng for help
Body movements (guarding)
• Guarding, rigid, tense posture,
fidgeting, pacing, rocking,
limping, resistance to moving

18. Types of Pain
Nociceptive Pain
Nociplastic
Neuropathic
Pain in response to
an injury or stimuli;
typically acute
Pain that arises from
altered nociceptive
function; typically
chronic
Pain that develops
when the nervous
system is damaged;
typically chronic
Fibromyalgia, irritable
bowel syndrome, non-
specific low back pain
Mixed pain syndromes (nociceptive and neuropathic)
Postoperative pain, sports
injuries, arthritis, sickle cell
disease, mechanical low
back pain
Post-herpetic neuralgia,
trigeminal neuralgia, distal
polyneuropathy, CRPS,
neuropathic low back pain,
diabetic peripheral neuropathy

19. Neuropathic Pain
• Neuropathic pain involves injury or
alteration of the normal sensory and
modulatory nervous system
• Multiple processes are capable of
producing sufficient neural alteration
to produce neuropathic pain
– Abnormal nerve regeneration
– Increased expression of
membrane sodium channels
– Disinhibition of modulatory processes
– Decreased expression of
mu-opioid receptors
• Pain occurs because injured nerves
(CNS or periphery) react abnormally
to stimuli or discharge spontaneously

20. Nociceptive Pain
American Pain Society, Principles of Analgesic Use, 7th Ed.
• Nociceptors = pain receptors in our tissues
– Nerve endings that process stimuli
(noxious and innocuous)
– Skin, GI tract, skeletal muscle,
joints, arteries, head, heart
• Nociceptive pain – arises from actual
or threatened damage to nonneural
tissue, due to activation of nociceptors
• Direction stimulation of afferent nerves
due to tissue injury or tumor infiltration
of skin, soft tissue, or viscera
• Proportionate to the stimulation
of the nociceptor
– More tissue damage = more pain

21. Pain Pathways
Dorsal Horns
Brainstem Dorsal Root
Ganglion
Afferent Pain Fiber
Thalamus

22. Transduction
Mechanical Thermal
Chemical
Action
Potential

23. Mediators of Peripheral Nociception
With thanks to Allan Basbaum and David Julius, University of California, San Francisco
Feeling physical pain
is vital for survival;
pain is the body’s early
warning system.

24. Pharmacologic Therapies
• Corticosteroids
– Dexamethasone has least
mineralocorticoid effect
– All can produce glucocorticoid effects
– Substantial side effects with
ongoing term use (psychosis,
proximal muscle wasting, and
bone loss)
• Nonsteroidal Anti-inflammatory
Drugs (NSAIDS)
– Analgesic, antipyretic, anti-inflammatory
– GI bleeding, bleeding, renal
dysfunction, cardiovascular effects
• Capsaicin

25. + + + + + - - - - - + + + + + +
- - - - - + + + + + - - - - - -
+ + + + + - - - - - + + + + + +
- - - - - + + + + + - - - - - -
Action Potential
Na+ Na+ Na+
K+
Na+ Na+ Na+
K+
Neuron
Conduction

26. Conduction
• C-fibers: small, unmyelinated, slow-conducting
– Transmits: dull, poorly localized,
diffuse, burning, aching pain
– Sensitive to: mechanical, thermal,
or chemical stimuli
• A-delta fibers: large, myelinated,
fast-conducting
– Transmits: well-localized, sharp pain
– Sensitive to: mechanical and
thermal stimuli
Impulse sent
along nociceptor
C fibers
A delta fibers
Spinal
Cord

27. + + + + + + + + + + + + + + + +
- - - - - - - - - - - - - - - -
Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+
K+
+ + + + + + + + + + + + + + + +
- - - - - - - - - - - - - - - -
r r r r r r r r r r
r
K+
r
K+
r
K+
r
Action Potential Blocked
r
r r r r r r r r r r
Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+
Neuron
Anticonvulsants/Anesthetics

28. Pharmacologic Therapies
• Lidocaine
– PHN and diverse group
peripheral NP conditions
– Mild skin reactions –
rash and erythema
– Blood level minimal up
to 4 patches/day
– Caution in hepatic failure and
other class I antiarrhythmics
– 12 hours on and 12 hours off
• Antiepileptic
– Carbamazepine/oxcarbazepine
efficacy in trigeminal neuralgia
– Lamotrigine, topiramate, valproic
acid, and phenytoin positive and
negative trials, more negative
than positive
– None considered first line except
carbamazepine and trigeminal
neuralgia

29. Dorsal Horn
Afferent
Pain Fiber
Spinothalamic
Tract
Transmission

30. Substance P
Spinothalamic
Tract Neuron
Primary
Afferent
Neuron

31. Opiate
Binding
Spinothalamic
Tract Neuron
Primary
Afferent
Neuron
Action of
Opiate Binding

32. Opioid Receptor Location

33. Opioids
• Potential benefits outweigh risks
• Patient has failed to adequately
respond to non-opioid and non-
pharmacological interventions
• Patient has moderate to severe
nociceptive or neuropathic pain
• Initiate a therapeutic trial
• Morphine
• Oxycodone
• Hydromorphone
• Fentanyl
• Oxymorphone
• Hydrocodone
• Codeine
• Oral
• Rectal
• Intravenous - PCA
• Subcutaneous
• Epidural - PCEA
• Intrathecal
• Transdermal
• Buccal
• Intramuscular

34. 2022 CDC Guideline
• Clinician recommendations
for patients aged ≥18 years
• Summary of current research
• Flexible; encourages patient-
centered decision-making
• Emphasizes the importance
of the individual and
clinical judgement
• This is a clinical tool, not a
law, regulation, or policy
https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm

35. Opioid Side Effect and Adverse Effects
Side Effects Adverse Events
Respiratory depression Death
Opiod-induced constipation (OIC)
(most common)
Addiction
Myoclonus (twitching or jerking) Overdose
Sedation, cognitive impairment Hospitalization
Sweating, miosis, urinary retention Disability or permanent damage
Allergic reactions Falls or fractures
Hypogonadism
Tolerance, physical dependence,
hyperalgesia

36. Opioid Risk Tool
• Opioid Risk Tool identifies persons
at higher risk of substance use
disorder and may be used to
identify patients that necessitate
additional monitoring
Scoring:
• ≤ 2: low risk
• ≥ 3: high risk
Opioid Risk Tool – OUD (ORT-OUD)
This tool should be administered to patients upon an initial visit prior to
beginning or continuing opioid therapy for pain management. A score
of 2 or lower indicates low risk for future opioid use discover; a score
of >/= 3 indicates high risk for opioid use disorder.
Mark each box that applies YES NO
Family history of substance abuse
Alcohol 1 0
Illegal drugs 1 0
Rx drugs 1 0
Personal history of substance abuse
Alcohol 1 0
Illegal drugs 1 0
Rx drugs 1 0
Age between 16-45 years 1 0
Psychological disease
ADD, OCD, bipolar, schizophrenia 1 0
Depression 1 0
Scoring totals

37. Informed Consent
• When initiating a pain treatment plan,
confirm patient understanding of
informed consent to establish:
– Analgesic and functional goals
of treatments
• Expectations
• Potential risks
• Alternatives
• Patient understanding
• Patient’s decision

38. Patient Provider Agreement
Reinforce Expectations for Appropriate and Safe Opioid Use
• Clarify treatment plans and goals
• One prescriber
• Consider one pharmacy
• Safeguards
– Do not store in medicine cabinet
– Keep locked (medication safe)
– Do not share or sell
• Prescriber notification for any
event resulting in a pain
medication prescription
• Follow-up plan
• Monitoring
– Pill counts
• Refill procedure
• Identify behaviors indicating
need for discontinuation
• Exit strategy
• Signed by patient, clinician
who goes over the form, and
the physician

39. Opioid Use Disorder DSM-5
1. Tolerance*
2. Withdrawal*
Loss Of Control
3. Using larger amounts and/
or for longer periods
4. Inability to cut down
on or control use
5. Increased time spent
obtaining, using,
or recovering
6. Craving/compulsion
Use Despite Negative Consequences
7. Role failure at work, home, school
8. Social, interpersonal problems
9. Reducing social, work,
recreational activity
10. Physical hazards
11. Physical or psychological harm
2 – 3 = mild | 4 – 5 = moderate | ≥ 6 = severe

40. Opioid Receptors in the Brain: Relationship
to Analgesia, OUD, and Withdrawal

41. The Cycle Of Substance Use Disorder
Neurotransmitters
•Dopamine
•Opioid peptides
•Corticotropin-
releasing factor
•Dynorphin
•Glutamate
Rewarding
euphoric
effect; limbic
system
Continue to take
drug; avoid
withdrawal
OUD Established,
preoccupation, and
craving; prefrontal cortex
impaired- impulsive
Binge/
Intoxication
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42. Everyone Is Vulnerable, But Who Is MOST Vulnerable
to Opioid Misuse or OUD?
• Those with low hedonic tone —
reduced capacity experience pleasure
• Those with psychiatric comorbidities
• Those with a genetic predisposition
to substance abuse (family history)
• The probability of long-term opioid
use increases most sharply in the
first days of therapy, particularly
after 5 days or 1 month of
opioids prescribed
19% of people with mental health
disorders in the US receive
51% of the prescribed opioids.

43. Differential Considerations
• Under-treated pain, including
disease progression, sometimes
termed “pseudoaddiction”
– Often benefit from co-analgesics
• Opioid induced hyperalgesia
• Paradoxical response where
increased opioids for pain treatment
actually creates increased pain
sensitivity/increase pain report
• Typically diffuse and less
defined quality
• Non-medical use of opioids
sometimes termed
“chemical coping”
• Used to treat anxiety,
insomnia, and existential suffering
• Misuse, abuse, or diversion

44. Opioid Misuse, Abuse, and Diversion
• Incorporate as part of the initial and
subsequent assessments
– Include patient, family
caregivers, frequent visitors
• Ongoing evaluation process
by IDG
• Regularly consider especially
when “red flag” situations arise:
– Pill counts “off”
– Repeated requests
for early refills
including after-hours
– Repeated requests for
dosing adjustments
because “it isn’t working”
– Conversations are
focused on opioids
– Caregivers are never
the same and/or won’t
identify themselves

45. Glutamate
Primary
Afferent
Neuron
­ NMDA Receptor Activation
­ Excitotoxicity
­
Ca++

46. Glutamate
NMDA Receptor
Antagonist
Spinothalamic
Tract Neuron
Primary
Afferent
Neuron

47. NMDA Receptor Antagonists
• Methadone
– Opioid receptor agonist and
NMDA receptor antagonist
• Ketamine
– Opioid sparing and deceases
pain intensity
– Side effects include nausea,
sedation, delirium, hallucinations,
psychotomimetic phenomena,
hypersalivation, and tachycardia
• Urinary and hepatobiliary toxicity
– Oral test dose (20mg po)
– Frequency every 6 to 8 hours
– Usually administer 100mg over
course of day and can increase
100mg daily to 800mg

48. Gabapentinoids
• Gabapentin and pregabalin
• Voltage-gated calcium channel
binder, decreases glutamate,
norepinephrine, and substance
leading to decreased
presynaptic release of
excitatory neurotransmitters
• Increased descending inhibition
• Efficacy in a variety of peripheral
nerve conditions and fibromyalgia
• Often used to be opioid sparing
• Generally well tolerated –
dizziness, sedation, and
peripheral edema
• Increased risk respiratory
depression and death with
concomitant use opioids
• Renal dosing

49. Anti-Spasm Drugs
• Baclofen
– 5-20 mg po TID
– Drowsiness,
dizziness, hallucinations
• Tizanidine
– 2 mg po TID
– Drowsiness
• Clonazepam
– 0.5 mg po BID – QID
– Sedating

50. Perception
Thalamus
Somatosensory Cortex
Associative Cortex

51. Cognitive and Behavioral Interventions
• Relaxation
• Guided imagery
• Distraction
• Cognitive reframing
• Support groups
• Pastoral counseling/prayer

52. Modulation
Serotonin (5HT)
Norephrinephrin (NE)
Brainstem
x

53. 5HT
+
NE
Antidepressants
Mechanism of Action
of Antidepressants

54. Antidepressants: Tricyclics
• Central and peripheral neuropathic pain
• Most studied agent, amitriptyline, has
substantial anticholinergic effects
• Alternate agents: nortriptyline, desipramine
• Usually sedating, administer at night
• Start low, 10mg at night titrate
gradually every 2 or 3 days, max
dose 150mg (cardiac)
• Cardiac toxicity (sinus tach and
vent ectopy)

55. Antidepressants: SNRI
• Venlafaxine
– Peripheral neuropathic pain
– Start low 37.5–75 po qd;
titrate gradually every
3-4 days; 150-225 mg/day
– Nausea (take with food)
– Cardiac disease
(EKG changes) and HTN
• Duloxetine
– Peripheral neuropathic pain
– FDA Approval fibromyalgia and
chronic musculoskeletal pain
(arthritis and low back pain)
– Reduce dose with renal disorder,
may be contraindicated with
hepatic impairment
– Nausea, dry mouth,
drowsiness, and dizziness

56. Afferent
Pain Fiber
Brainstem
Cognitive
Behavior
Therapy
NSAIDs/DEX
LA/Anticonvulsants
Opioids/NMDA/α
2-δ Ca Channel
TCA/SNRIs

57. Pharmacologic Management by Pain Etiology
Nociceptive Pain
Nociplastic
Neuropathic
Antihistamine
Acetaminophen
Opioids and NMDA blockers
Nerve blocks
NSAIDs
Topical/transdermal treatments
Anticholinergic
Anticonvulsants
TCAs and SNRIs
Other serotonin agents
Anticonvulsants
Opioids and NMDA blockers
Nerve blocks
TCAs and SNRIs
Generally not
opioid responsive

58. Important Considerations
• Pain is often multifactorial and
uniquely impacts each individual, and
benefits from non-pharmacologic and
pharmacologic approach.
• Establishing a positive patient-
physician partnership provides an
important foundation that will
optimize treatment outcomes.
– Develop a mutual understanding
of treatment goals/expectations.
– Build rapport and trust.
– Encourage patients take on an
active role in managing their pain.
• Substantial improvement
in function and quality of life
can be anticipated even
if pain is not eliminated.
• Persistent pain is treatable,
but it is not curable.