The Ins and Outs of Pain

THE INS AND OUTS OF PAIN

Kyle P. Edmonds, MDFellow, Scripps Health & The Institute for Palliative Medicine at San Diego

Hospice

Adapted from the Palliative Care International Curriculum Series

Editor, Frank R. Ferris, MD

OBJECTIVES

• Review the definitions, pathophysiology & classifications of pain.

• Perform a standardized assessment of pain and state why it is important for team communication.

• State how Cmax and half-life relate to opioid dosing.

• Describe the hallmark of addiction and the low likelihood of occurrence in pain management.

International Association for the Study of Pain ( IASP ):

“An unpleasant sensory and emotional experience

associated withactual or potential tissue damage.”

PAIN

Margo McCaffery:

“Pain is whatever the person says it is…”

PAIN

TOTAL PAINCICELY SAUNDERS 1964

Patient

with Pain

Physical

Emotional

Existential

Social

MECHANISM OF PAIN- DESCARTES

NOCICEPTOR

• Nerve cell

• Activation• Thermal • Chemical• Mechanical

• Transmits signal

NOCICEPTION

• Activation of receptors

• Transmitting

• Processing

• Leads to pain perception

BASIC STEPS: PAIN PROCESSING

• Transduction

• Transmission

• Perception

• Modulation

Mechanical Thermal

Chemical

Judith A. Paice, AAHPM, 2008

Aδ or C fibers

PAIN TRANSDUCTION

TRANSMISSION

• Stimulus to cord

• Cord to brain stem

• Brain stem to higher cortex

Thalamus

Somatosensory Cortex

Associative Cortex

Judith A. Paice, AAHPM, 2008

TRANSMISSION

PERCEPTION

• Experience• Conscious

• Multidimensional

• Interaction of transmission/transduction

MODULATION

• Changing

• Inhibiting

• Spinal cord level

PAIN PROCESSING

• Transduction

• Transmission

• Modulation

• Perception

CLASSIFICATION OF PAIN

• Physiologic• Nociceptive

• Neuropathic

• Mixed

• Temporal• Acute

• Chronic

NOCICEPTIVE PAIN

• Somatic

• Visceral

• “Sharp” “Aching” “Throbbing”

NEUROPATHIC PAIN

• Damaged or dysfunctional nerves

• Central

• Peripheral

• “Burning” “Tingling” “Numbness” “Electric”

MIXED PAIN

• Experiencing • nociceptive

and

• neuropathic

CLASSIFICATION OF PAIN

• Physiologic• Nociceptive

• Neuropathic

• Mixed

• Temporal• Acute

• Chronic

TEMPORAL CLASSIFICATION: ACUTE

• Sudden or recent onset

• Identifiable cause

• Short duration

• Sympathetic response

TEMPORAL CLASSIFICATION: CHRONIC

• Persistent

• May have no obvious cause

• Prolonged functional impairment

• No sympathetic response

INTERVAL SUMMARY

Understanding the pathophysiologyleads to improved assessment and

targeted management that will improve outcomes

PAIN ASSESSMENT

1. Location2. Description (type)3. Change over time4. Severity (0 – 10)5. Effect of

treatments• Benefit (+)• Unwanted effects (-)

1. LOCATION

• Where is it ? • Does it move ?

2. DESCRIPTION

• What does the pain feel like ?

• Does it ever feel burning or shooting ?

• How does the pain impact your life ?

• Constant

• Breakthrough

• Intermittentacute

3. CHANGE OVER TIME

4. PAIN SEVERITY = 5TH VITAL SIGN

29

5. EFFECT OF TREATMENTS

• Therapies tried• What worked ?• What didn’t work ? • Any affects you

didn’t like ?

EXAMINATION

• General exam• Changes in behavior• Focused exam• Psychological exam

INTERDISCIPLINARY TEAM

• Physician•Assess•Diagnose•Prescribe•Monitor•Communicate

• Nurse•Assess•Deliver•Monitor•Teach•Communicate

• Pharmacist•Assess•Provide•Monitor•Teach•Communicate

INTERVAL SUMMARY

Assessment of pain requires a thoughtful history and physical. Standardizing the

process helps prevent miscommunication.

PAIN MANAGEMENT: DEFINITIONS

• Opioid: anything that binds the opioid receptor

• Opiate: derived from the opium poppy (Papaver somniferum)

• Narcotic: archaic term, associated with illicit use

35

PAIN MANAGEMENT PRINCIPLES

• Don’t delay control

• Unmanaged pain nervous system changes

• Treat underlying cause

WHO LADDER

1, Pain 1 – 3

2, Pain 4 – 6

3, Pain 7 – 10

Morphine

Hydromorphone

Fentanyl

Oxycodone

Methadone

Levorphanol

± Adjuvants

Codeine

Tramadol

A / Codeine

A / Hydrocodone

A / Oxycodone

A / Dihydrocodeine

± Adjuvants

ASA

Paracetamol / Acetaminophen

NSAID’s

± Adjuvants WHO. Geneva, 1996.

Pla

sma

Co

nce

ntr

atio

n

0 Time

AbsorptionExcretion

First Order KineticsWhen biological effect

follows plasma concentration

Pla

sma

Co

nce

ntr

atio

n

0

Maximum Concentration ( Cmax )

20

10

= maximum concentration during the dosage interval

Cmax

Time ( hours )4

Pla

sma

Co

nce

ntr

atio

n

0 Time ( hours )

Time to MaximumConcentration ( t Cmax )

20

10

1 4

= time it takes to get to maximum concentration

Cmax MorphinePO / PR

Cmax = 1 hour

Pla

sma

Con

cen

trat

ion

0 Half-life (t1/2) Time

IV

PO / PR

SC / IM

Cmax

Time to MaximumConcentration ( t Cmax )

Pla

sma

Co

nce

ntr

atio

n

0

Half-Life ( t ½ )

Morphineall routes

t ½ = 4 hours

20

10

= time it takes for the body to excrete half the dose

Time ( hours )4

CLEARANCE CONCERNSMORPHINE

Liver

•Morphine M3G . . .

M6G . . .

Analgesia CNS

+ +++

++++

Collins SL, et al. J Pain Symptom Manage. 1998.Mercadante S, Arcuri E. J Pain. 2004.

Urine90 – 95 %

PRINCIPLEFOR CONTINUOUS PAIN

For constant pain

• To achieve steady-state, dose routinely every

half-life ( t ½ )

CONTINUOUS PAIN PRINCIPLE

Pla

sma

Co

nce

ntr

atio

n

0

Dosing every half-life ( t ½ )Oral morphine = 4 hours

164 8 12Time ( hours )20 24

50%75%

87.5%93.75%

97%100%

Pla

sma

Co

nce

ntr

atio

n

0 Time

Steady state after 5 half-livesMorphine ≈ 20 hours

Peak

TroughConcentration

needed to control pain

Concentration where side-effects

start to occur

PRINCIPLEFOR BREAKTHROUGH PAIN

• Dose once every Time to Cmax

• PO 1 h

• Dose =10% of total 24 hr routine dose

Pla

sma

Con

cen

trat

ion

0 Time

Cmax

Breakthrough Pain

PO / PR≈ 1 hr

OPIOID ADVERSE EFFECTS

Uncommon

• Bad dreams / hallucinations

• Delirium

• Myoclonus / seizure

• Pruritis / urticarial

• Respiratory depression

• Urinary retention

Common

• Constipation

• Dry mouth

• Nausea

• Sedation

• Sweats

EQUIANALGESIC DOSES

Oral/Rectal Analgesic IV/SC/IM

150 Codeine --

15 Hydrocodone --

15 Morphine 5

10 Oxycodone --

3 Hydromorphone 1

51

MORPHINE PO OXYCODONE POMorphine 15 mg PO = Oxycodone 10 mg PO

• Patient is on Morphine ER 90mg BID PO

• Oral Morphine Equivalent?

• (90 mg x 2 = )180mg

• This equals how much Oxycodone?

• ( 180 mg x 15 / 10 =) 120mg

• How much Oxycodone ER?

• 60mg PO BID

MORPHINE PO HYDROMORPHONE IV

Morphine 15 mg PO = Morphine 5 mg IV = Hydromorphone 1 mg IV

• Patient is on Morphine IR 20mg q2hrs PO PRN

• Now can’t take PO, how much HM?

• ( 20mg / 3 then 6.67 mg / 5 =) 1.3mg IV

MORPHINE PO HYDROMORPHONE IV

Morphine 15 mg PO = Morphine 5 mg IV = Hydromorphone 1 mg IV

• Patient is on Morphine ER 90mg BID (OME 180mg)

• How much IV Hydromorphone in a day?

• ( 180mg / 3 then 60 mg / 5 =) 12mg IV / 24hrs

MORPHINE PO HYDROMORPHONE IV

Morphine 15 mg PO = Morphine 5 mg IV = Hydromorphone 1 mg IV

• Patient is getting 8mg IV Morphine hourly PRN without relief

• What is this equal to in Hydromorphone IV?

• ( 8 mg / 5 =) 1.6 mg

INTERVAL SUMMARY

Understanding the way these medications enter and leave the body can help you safely and effective treat pain. Always

have someone independently check your work when changing medications.

SARAH, 43 YO

• Metastatic colorectal CA

• Sacral plexus destruction

• Multiple opioid trials• Pain 6 / 10

• Drowsiness

• Confusion

58

“TOTAL PAIN”

ADJUVANT THERAPIES

• Pharmacological• Interventional Anesthesia

• Non-pharmacological• Acupuncture

• Biofeedback

• TENS

• Counseling

• Integrative therapies

ADJUVANT EVIDENCE

• Therapies extrapolated from non-cancer pain

• Few RCTs

• Very few comparative trials

GUIDING THERAPY

• Diagnosis

• Assessment

• Efficacy

• Safety / tolerability

• Ease of use

• Cost

OPIOIDS

• Nociceptive pain > neuropathic pain

• First-line for mod to severe neuropathic pain

• Titrate to effect or side-effect

METHADONE

• Long half-life

• NOT first order kinetics

• Experienced palliative care / pain experts

• Coanalgesic: 2.5 – 5+ mg

• Cost PO << parenteral

GABAPENTINOIDS

• Sodium channel antagonist

• Positive RCT’s

• NNT less favorable than TCAs

• First-line 2º safety

• Trial gabapentin

•Start 100-300 mg qhs

•Daily, increase 100 mg q8h

•Effective 900 - 1800 mg / 24 hr

•Max 3600 - 5400 mg / 24 hr

• If ineffective, pregabalin

•Start 25-75 mg q12h

•Increase 25 mg q12h

•Effective 100-150 mg / 24 hr

•Max 300 - 600 mg / 24 hr

GABAPENTINOIDS…

ANTIDEPRESSANTS

• 3º amine TCAs (amitriptyline)

• 2º amine TCAs (desipramine, nortriptyline)

• Mixed SNRIs (duloxetine, venlafaxine)

• SSRIs (citalopram, paroxetine)

OTHER ANTICONVULSANTS

• excitation

• Limited data, trial-and-error

• Newer drugs have better safety profiles

CORTICOSTEROIDS

• Limited data, widely used in • Bone pain

• Neuropathic pain

• Lymphedema

• Other conditions

• Dexamethasone• Start high dose 8+ mg daily

• Taper to lowest effective dose

OTHER OPTIONS

• Lidocaine (IV or SC)

• Sodium channel blockade

• Good evidence

• Ketamine (PO, IV, SC)

• NMDA blocker

• Dose-limiting psychological effects

SARAH, 43 YO, CA COLON

• Touch

• Simplify meds ( ! )

• Address total suffering

• Feb 14…Pain 6 / 10

INTERVAL SUMMARY

Sometimes the best long-acting medicine for a patient may not be an opioid. Poor

opiate-responsiveness is a sign that multimodal therapies may be necessary

to achieve pain relief.

CLARIFYINGADDICTION

TOLERANCE

• Reduced effectiveness over time

• Not clinically significant with chronic dosing

• Suspect disease progression

PHYSICAL DEPENDENCE

• Process of neuro-adaptation

• Abrupt cessation withdrawal

• Titrate down if stopping

• Avoid antagonists

DRUG DIVERSION

• Regulation

• Record keeping

• Accountability

PSEUDO-ADDICTION

• Most common cause of apparent drug ‘ failure ’ is under-dosing

• Behavior LOOKS like drug seeking

ADDICTION: CHARACTERISTICS

• Psychological dependence

• Compulsive use

• Loss of control over drugs

• Loss of interest in pleasurable activities

ADDICTION: HALLMARK

• Continued use of drugs in spite of harm

• Rare outcome of pain management

SUBSTANCE USERS

• Can have pain too

• Treat with compassion

• Consultation with pain or addiction specialists

INTERVAL SUMMARY

True addiction is rare in the management of pain and pain can occur in those with a

history of substance use.

SUMMARY

81

• Pain may be nociceptive, neuropathic or both and the history tells you which.

• A standardized approach to the assessment of pain helps prevent miscommunication.

• For constant pain, dose on the half-life (q4hrs). For breakthrough pain, dose on the Cmax (route-dependent).

• True addiction is uncommon in pain management.

THE INS AND OUTS OF PAIN

Kyle P. Edmonds, MDFaculty, UCSD Division of Palliative Medicine

928.853.1483

Kyle.p.edmonds@gmail.com

Kylepedmonds.com