Pain Management

EO 004.12

Learning Objectives

• Describe the principles of pain management for acute and chronic pain that impact on patient care

• Select the most appropriate analgesic for an individual patient to maximize the benefits that can be expected from therapy

• Communicate important aspects of analgesic therapy to patients to improve the odds of therapy being successful

References

• Therapeutic Choices– Chapters 11,12

• Current Medical Diagnosis and Treatment– Chapters 20, 24

Outline

• Pain Definitions• Epidemiology• Pathophysiology• Pain Pathways• Drug Treatment

• Mild Analgesics• Opioid Analgesics• Adjuvant Analgesics• Miscellaneous Analgesics

• Cases

Pain Definitions

• What is pain?

• What purpose does pain serve?

• How can I assess an individual’s pain?

• What are the implications of poorly managed pain?

Analgesia, Anesthesia And Pain

• Analgesia• Anesthesia• Pain

1. Acute2. Chronic3. Neuropathic4. Bone5. Palliative Care

Acute And Chronic PainCharacteristic Acute Pain Chronic Pain Relief of Pain Highly

Desirable Highly

Desirable Dependence and

Tolerance to Medication Unusual Common

Psychological Component Usually Not Present

Often a Major Problem

Organic Cause Common Often Not Present

Environmental Contributions and Family

Involvement

Small

Significant

Insomnia Unusual Common Treatment Goal Cure Functionality

Somatic, Visceral And Neuropathic Pain

Characteristic Somatic Pain Visceral Pain Neuropathic Pain Location Localized Generalized Radiating or Specific

Patient Description Pin Prick or Stabbing or Sharp

Ache or Pressure or Sharp

Burning or Prickling or Tingling or Electric or Shock-like or

Lancinating Mechanism of Pain A-delta Fiber

Activity Located in the Periphery

C-Fiber Activity Involved Deeper

Innervation

Dematomal (peripheral) or non-dematomal (central)

Clinical Examples Superficial Laceration,

Superficial Burns, IM Injections,

Venous Access, Otitis Media, Stomatitis,

Extensive Abrasion

Periosteum, Joints, Muscles, Colic and

Muscle Spasm Pain, Sickle Cell,

Appendicitis, Kidney Stone

Trigeminal Neuralgia, Avulsion Neuralgia, Post-traumatic

Neuralgia, Peripheral Neuropathy (Diabetes, HIV), Limb

Amputation, Herpetic Neuralgia

Most Responsive Treatment

Cold Packes, Tactile Stimulation,

Acetaminophen, NSAIDs, Opioids, Local Anesthetics

(Topical or by Infiltration)

NSAIDs, Opioid Via Any Route, Intraspinal

Local Anesthetic Agents

Anticonvulsants, Tricyclic Antidepressants, Neural

Blockade

Pain Epidemiology - Overview

• Fifty million Americans are partially or totally disabled because of pain

• Fifty percent of seriously ill hospitalized patients report pain (15% had moderate to severe pain at least 50% of the time)

• Seventy percent of chronic pain patients in nursing homes had pain despite treatment

• Fifty percent of people in a British study of community-dwelling patients had pain (in 50% of those the pain was significant)

Epidemiology – Neuropathic Pain

Pain pathways

• Ascending stimulating pathways– Noxious stimulus activates afferent

neurons• A fibres – fast transmission, sharp stinging –

acute pain• C fibres – slow transmission, dull, aching –

chronic pain

– Stimulate the CNS via spinal interneurons• Substance P and Glutamate

Pain Pathways

• Descending inhibitory pathways– Originate in midbrain– Release inhibitory neurotransmitters

• Serotonin and norepinephrine• Enkephalins

• Gate hypothesis– Pain transmission up the ascending

pathway can be modulated by activity of other neurons

Pain Perception

• Nociceptive process

• Physiologic response

• Emotional response

• Psychological framework

Assessing Pain

• Provocative causes/Palliative aids

• Quality

• Radiation

• Severity

• Timing

An Approach To Acute PainPatient (pt) has

pain or is likely to have pain

Critical first step:detailed history and

focused physical exam

Determine mechanism of pain – pt may report more

than one type

Arrange diagnostic workup and treat

pain per information available

Next page

Pt reports

localized pin prick, sharp or stabbing pain

Pt reports

generalized ache or pressure

Pt reports radiating,

burning, tingling or lancinating

pain

Somatic Pain Visceral Pain Neuropathic Pain

Treatment Choices:

1. tactile stimulation

2. cold packs 3. acetaminophen 4. NSAIDs 5. opioids 6. local

anesthetics (topical or infiltration)

Treatment Choices:

1. opioids 2. NSAIDs 3. local

anesthetics (intraspinal)

Treatment Choices: 1. anticonvulsants 2. tricyclic antidepressants 3. neural blockade 4. opioids

See next page

Specific interventions: 1. Titrate medication dose up/down 2. Patient education 3. Further diagnostic workup 4. Specialty consult (surgery, etc.) 5. Procedures (neural blocks) 6. Behaviour and cognitive

interventions 7. Adjuvant therapy

Adequate pain relief?

Yes No Confident of pain

mechanism?

Yes

No

Revisit “critical

first steps”

Side effects?

No

Yes

Follow-up patient

instructions

Select an alternative treatment

Side effect management

End

An Approach To Chronic Pain

Approach To Chronic Pain

Knowledge Of Disease

Quality Of Pain Burning Lancinating Aching Movement-

related

Quantity Of Pain Pain Intensity

Scale Rated By Patient Rating Of 1-5

Diagnosis Of Etiology

Nerve Bone Soft

Tissue

See Next Page

Approach To Chronic Pain

Treatment Plan Guide Modified WHO

Analgesic Ladder

Mild Pain (1-2)

Moderate Pain (2-3)

Severe Pain (4-5)

Non-opioid +/-

Adjuvant

Weak Opioid +/- NSAID

+/- Adjuvant

Strong Opioid

+/- NSAID +/- Adjuvant

Reassess Relief And

Modify Plan If Needed

END

Assessing An Individual’s Pain

Assessing An Individual’s Pain

Analgesics• Mild

– Acetaminophen, ASA, NSAIDS

• Opiates– Moderate – codeine– Severe - morphine, meperidine and others

• Adjuvants– Tricyclic Antidepressants (TCAs)– Anti-Epileptic Drugs (AEDs)

• Miscellaneous– Local Anesthetics, Capsaicin, Cannabis

Acetaminophen

• Works by inhibiting the synthesis of prostaglandins in the central nervous system and peripherally by blocking pain impulse generation

• Has no significant anti-inflammatory effects• Is most responsive to somatic type pain of

mild to moderate intensity• Has an opioid sparing effect when used in

combination with narcotics

ASA• Works by irreversibly acetylating

cyclooxygenase (COX) to inhibit prostaglandin synthesis

• Similar efficacy, potency, and time-effect curve as acetaminophen

• Is most responsive to somatic type pain of mild to moderate intensity

• Largely replaced by equally or more effective but safer NSAIDs for most analgesic indications

NSAIDs• NSAIDs are indicated for mild to moderate pain,

especially if there is an inflammatory or boney component

• NSAIDs work by non-covalently binding to COX• There is a high inter-patient variability in response to

NSAIDs, so a trial of a different NSAID may be appropriate if a patient doesn’t respond to an initial course

• In single full doses, most NSAIDs are more effective than A.S.A. or acetaminophen and some have shown equal or even greater analgesic effect than usual doses of oral opioids

Mild Analgesics – Summary

Benefits:

1. Useful for mild to moderate somatic pain

2. Well tolerated

3. Available in many forms

4. Low abuse potential

Limitations:

1. Ceiling effect

2. Not useful for more severe pain, especially neuropathic or visceral type pain

3. Frequently require multiple daily doses for analgesia

Opioids - Background

• Opioids are used for all types of moderate to severe pain but are most effective for visceral and somatic pain – much less so for neuropathic pain, often necessitating adjuvant therapies

• Opioids do not decrease sensitivity to touch, sight or hearing at therapeutic doses

Opioids – SummaryOpioid Parenteral Dose

(mg) (IV/IM/SC)

Oral Dose (mg)

Interval (h)

Morphine 10 30 4 Morphine Controlled Release

10 30 8-12

Hydromorphone 1.5 7.5 4 Codeine 130 200 4

Oxycodone - 15-30 4 Oxycodone Controlled Release

- 15-30 8-12

Levorphanol 2 4 4 Meperidine 75 300 2-3 Methadone 5 5 6-8

Fentanyl 0.1-0.2 - 1-2 Transdermal Fentanyl – Rember 1:2:3

25mg/day morphine IV = 50 mcg/hr q72h fentanyl patch = 75mg/day morphine PO

Opioids –Benefits And Limitations

Benefits:

1. Useful for moderate to severe pain of somatic or visceral origin

2. No ceiling effect for most agents

3. Available in many forms, including extended release

4. Predictable adverse effect profile

Limitations:1. Not as efficacious vs.

neuropathic pain2. Titration required due to

physical tolerance3. Numerous adverse

effects including physical and psychological dependence

4. Special prescribing and dispensing practices may apply

TCAs – Background

• These medications are used as complementary therapy to primary analgesics in neuropathic pain

• Meta-analyses indicate TCAs are approximately 50% effective for patients with a number of painful neuropathic conditions

• TCAs are first line due to low cost and efficacy when the alternatives like AEDs are considered (although there are exceptions; notably trigeminal neuralgia)

TCAs - Indications

• Pain syndromes responsive to TCAs include:

1. Post-herpetic neuralgia2. Peripheral neuropathy (i.e. diabetic

neuropathy, HIV neuropathy, idiopathic neuropathy, etc)

3. Central pain (damage specifically to the brain or spinal cord from strokes, multiple sclerosis, limb amputations or trauma)

TCAs - MOA

• Postulated mechanisms include:1. Blockade of norepinephrine,

2. Antagonism of histamine and muscarinic cholinergic receptors,

3. Alpha-adrenergic blockade, or

4. Suppression of C-fiber afferent-evoked activity in the spinal cord

AEDs – Background

• These medications are used as complementary therapy to primary analgesics in neuropathic pain

• Meta-analyses indicate AEDs, although widely used in chronic pain (approximately 5% of all AEDs prescribed in the U.S. are for pain management), have surprisingly few trials to show analgesic effectiveness

AEDs – Background

• There is no evidence AEDs are effective for acute pain

• In chronic pain syndromes other than trigeminal neuralgia, AEDs should be withheld until other interventions are tried

• Number-needed-to-harm for major effects weren’t significant for any drug vs. placebo

• Number-needed-to-harm for minor effects ranged from 2.5 (confidence interval [CI] 2.0-3.2) for gabapentin to 3.7 (CI 2.4-7.8) for carbamazepine

AEDs - Indications

• AEDs have different indications• Carbamazepine is the intervention of choice

for trigeminal neuralgia• Pain syndromes AEDs are used in include:

1. Trigeminal neuralgia2. Peripheral neuropathy3. Central pain4. Post-herpetic neuralgia5. Complex regional pain syndrome (formerly reflex

sympathetic dystrophy)

AEDs - MOA

• The precise mechanism of action of AEDs remains uncertain

• The standard explanations include1. Enhanced gamma-aminobutyric acid

(GABA) suppression2. Stabilization of neural cell membranes or

possibly3. Action via N-methyl-D-aspartate (NMDA)

receptor sites

AEDs – SummaryAgent Indications Contra-

indications Most Common Side

Effects Carbamazepi

ne (Tegretol ®)

Central Pain (CP), Peripheral Neuropahty

(PN), Trigeminal Neuralgia

(TN)

Liver abnormalities, bone marrow suppression,

hypersensitivity to TCAs

Sedation, dizziness, ataxia, confusion,

nausea, liver toxicity, blod dyscrasias,

Stevens-Johnson Syndrome

Gabapentin (Neurontin ®)

Complex Regional Pain Syndrome (CRPS),

Post-Herpetic Neuralgia (PHN), PN,

Post-Stroke Pain, Spinal Cord Injury, TN

Hypersensitivity Sedation, dizziness, confusion, peripheral edema, weight gain

Phenytoin CP, PHN, PN Bradycardia 2°-3° heart block, hypersensitivity

Sedation, dizziness, ataxia, confusion, nausea, gingival

hyperplasia, peripheral

neuropathy, Stevens-Johnson

Syndrome

Adjuvant Analgesics – Summary

Benefits:1. May improve pain control

in conditions resistant to other analgesics

2. May allow for dosage reduction of other analgesics

3. Can be used in the long term management of chronic pain and associated conditions (i.e. depression)

Limitations:1. Not effective for acute

pain2. Not useful as

monotherapy3. Poor evidence

supporting use in many conditions

4. Adverse effects often occur before therapeutic effects

Local Anesthetics

• Can provide relief of acute or chronic pain• Are administered by injection (into the joints,

epidural or intrathecal space, along nerve routes or in a nerve plexus) or topically (ex. lidocaine jelly, eutectic mixtures of local anesthetics [EMLA ® = lidocaine and prilocaine])

• Work by blocking nociceptive transmission and interrupting sympathetic reflexes

• Are often combined with opioids for synergy

Local Anesthetics

• Disadvantages in the use of local anesthetics include:

1. Need for skillful technical application

2. Need for frequent administration

3. Need for highly specialized monitoring and follow-up procedures

Capsaicin

• Indicated in the topical treatment of pain associated with postherpetic neuralgia, arthritis, diabetic neuropathy and postsurgical pain

• May also be useful for psoriasis, chronic neuralgias unresponsive to other treatments and intractable pruritus

Capsaicin

• Commonly available as a cream of differing strengths:• Zostrix ® = 0.025%• Zostrix-HP ® = 0.075%

• Induces the release of substance P from peripheral neurons and after repeated application depletes substance P and prevents it’s reaccumulation

Capsaicin

• Onset of action = 14-28 days with regular application (3-4 times daily)

• Maximum effect may take up to 6 weeks• Duration of effect after an application =

several hours• Transient burning occurs in > 30% of

patients, which usually diminishes with repeated use

• Also causes itching, stinging, erythema and cough in 1-10% of patients

Cannabis

• Three quarters of British doctors surveyed in 1994 wanted cannabis available on prescription

• Humans have cannabinoid receptors in the central and peripheral nervous system

• Cannabinoids are analgesic and reduce signs of neuropathic pain in animal tests

• Some evidence suggests that cannabinoids may be analgesic in humans

Cannabis

• No studies have been conducted on smoked cannabis

• The predominant adverse effect was central nervous system depression which was common at higher doses

• Cardiovascular effects were generally mild and well tolerated

Cannabis

• The best that can be achieved with single dose cannabinoids is an analgesic effect equivalent to 60mg of codeine (or a number needed to treat of 16 patients for at least a 50% reduction in pain)

• Cannabinoids widespread introduction for pain management is therefore undesirable

Conclusion

A Bill Of Rights

I have the right to have my reports of pain accepted and acted on by health care professionals

I have the right to have my pain controlled, no matter what the cause or how severe it may be

I have the right to be treated with respect at all times. When I need medication for pain, I should not be treated like a drug abuser

Principles Of Pharmacotherapy

• Always ask the patient if pain is present and assess the characteristics of pain

• Identify the source of pain• Select the most effective analgesic with

the fewest adverse effects• Properly titrate the dose for each

individual and administer for an adequate duration

Principles Of Pharmacotherapy

• Always consider around-the-clock (ATC) regimens for acute and chronic pain

• Use as-needed (PRN) regimens for breakthrough pain or when acute pain displays great variability and/or has subsided greatly

• Assess for adverse effects, particularly the constipation seen with opioids

Principles Of Pharmacotherapy

• Avoid excessive sedation by titrating opioids effectively

• Adjust the route of administration to meet the needs of the patient

• Whenever possible use the oral route• When converting from one opioid to

another, use the equianalgesic dose and then titrate

Principles Of Pharmacotherapy

• Do not use placebo therapy to diagnose psychogenic pain

• Consider the use of capsaicin, tricyclic antidepressants and anticonvulsants when treating neuropathic pain

• Use a multidisciplinary approach and nonpharmacologic strategies when possible

Pitfalls In Analgesic Therapy

1. Overestimating the analgesic efficacy of a drug

2. Underestimating the analgesic requirement of the patient

3. Prejudice against the use of analgesics that may prevent objective therapy

4. Lack of knowledge in analgesic pharmacology

Pitfalls In Analgesic Therapy

5. Patient non-compliance because of fear of addiction

6. Patient not communicating with caregivers for fear of being labeled a drug addict

7. Patient wants to please by not complaining

8. Patient does not know how or is afraid to communicate with caregiver