Acute Pain: Mechanisms, Management, and Treatment Options

Acute Pain: Mechanisms, Management, and Treatment Options
ACUTE PAIN
IT WILL BE POTENTIAL TO KILL YOUR
PATIENTS
Mulyono Soedirman
FK UNHAS / RSPAD GATOT SOEBROTO
JAKARTA
Overview
Pain: Definition and Features
Physiologic Consequences of Acute Pain
JCAHO and Pain Management
Characteristics of Acute, Chronic, Peripheral
Neuropathic Pain
Assessment of Pain and Pain Relief
Pain Mechanisms
Role of Prostanoids in Pain
Treatment Options for Acute Pain
Other Approaches
Acute Pain Services
Pain
Definition and Features

Definition
“Pain is an unpleasant sensory and emotional experience

associated with actual or potential tissue damage or
described in terms of such damage.”
International Association for the Study of Pain. Pain. 1979;6:249.

Features of Acute Pain

• Onset
• Intensity
• Somatic vs visceral
• May be referred
Siddall PJ, Cousins MJ. In: Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia
and Management of Pain. 3rd ed; 1998:675–713.


• General stress response/neuroendocrine
• Respiratory
• Cardiovascular
• Gastrointestinal/urinary
• Musculoskeletal
Bonica JJ. The Management of Pain. 2nd ed. Vol. 1; 1990.

General Stress Response
Endocrine/Metabolic
• ↑ ACTH, cortison, catecholamines, interleukin-1
• ↓ insulin
Water/Electrolyte Flux
• H2O, Na+ retention
ACTH = adrenocorticotropic horrmone

Kehlet H. Reg Anesth.1996;21(6S):35–37.
Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.
Respiratory Effects
Acute
Pain
↓ Tidal ↓ Vital ↓ FRC ↓ Alveolar ↓ Mobility

volume capacity ventilation
Atelectasis
Hypostatic pneumonia
V/Q inequality
FRC = functional residual capacity; V/Q = ratio ventilation:perfusion of the lung

Craig DB. Anesth Analg. 1981;60:46.
Respiratory Effects (Cont’d)

Acute
Pain
Muscle spasm
Muscle splinting
Impaired
ventilation
Cough suppression
Lobular collapse Hypoxemia
Infection/pneumonia
Cardiovascular Effects
Acute
Pain
Coronary Sympathetic
vasoconstriction overactivity
↑ Anxiety, pain ↑ HR, ↑ PVR, ↑ BP, ↑ cardiac output

• Ischemia
• Angina
• MI Ischemia
MI = myocardial infarction; HR = heart rate; PVR = peripheral vascular resistance; BP = blood

pressure
Bowler DB, et al. In: Cousins MJ, Phillips GD, eds. Acute Pain Management; 1986:187–236.
Effects on Peripheral Circulation
Acute
Pain
↓ Limb blood flow1

↓ Venous emptying2
↑ Venous thrombosis/embolism3
1. Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.
2. Modig J, et al. Acta Anaesth Scand. 1980;24:305–309.
3. Modig J, et al. Anesth Analg. 1983;62:174–180.
Gastrointestinal and Urinary Effects
Acute
Gastrointestinal Pain Urinary
↑ Intestinal secretions
Sympathetic
↑ Smooth muscle ↑ Urinary sphincter
overactivity
sphincter tone activity
↓ Intestinal motility
Urinary retention
Nimmo WS. Br J Anaesth. 1984.56:29–37.
Musculoskeletal Effects
Acute
Pain
↑ Muscle
spasm
↑ Sensitivity of peripheral
Sympathetic
nociceptors
overactivity
Musculoskeletal Effects (Cont’d)
Acute
Pain
↓ Mobility
Reflex
vasoconstriction
• Impaired muscle
metabolism
• Muscle atrophy
• Delayed normal
muscle function
Effects on Pain-Signaling Systems
Acute
Pain
↑ Peripheral nociception ↑ Nerve excitability
• Hyperalgesia (1° + 2°)

Prolonged pain • Allodynia
Chronic pain Damaged spinal

pain-signaling systems
Psychologic Effects
Acute
Pain
Anxiety
Sleep deprivation
Depression
Other Effects of Acute Pain
• Wound repair
• Impaired immunocompetence
• Hypercoagulable state
Drucker W, et al. J Trauma. 1996;40(3):S116–122.

Jorgensen L, et al. Br J Anaesth. 1991;66:8–12.
Advantages of Effective Pain Management
• Patient comfort and satisfaction1,2,3

• Earlier mobilization4
• ↓ hospital stay3,4
• ↓ costs4
1. Eisenach JC, et al. Anesthesiology. 1988;68:444–448.

2. Harrison DM, et al. Anesthesiology. 1988;68:454–457.
3. Miaskowski C, et al. Pain. 1999;80:23–29.
4. Finley RJ, et al. Pain. 1984;2:S397.
JCAHO and Pain Management

Joint Commission on Accreditation

of Healthcare Organizations
• New standards in 2000–2001; scoring begins in 2001

• Record pain as the 5th vital sign
• Interdisciplinary management with needs assessment
• Patient’s right to pain assessment
• Monitor pain intervention responses
• Provide pain management education
Joint Commission on Accreditation of Healthcare Organizations. Jt Comm Perspect. 1999;19(5):6–8.

Sklar DP. Ann Emerg Med. 1996;27:412–413.
Pain: The Fifth Vital Sign
• Pain should be considered the “fifth vital sign”

• Patients should be assessed for pain every time pulse,
blood pressure, core temperature, and respiration are
measured
• Healthcare professionals should recognize a report of
unrelieved pain as a “red flag”
American Pain Society Quality Improvement Committee. JAMA. 1995;1847–1880.

JCAHO Revised Standards: The Patient’s Rights
• Patients have the right to appropriate assessment and

management of pain
• The patient’s right to pain management is respected and
supported
• Patients are involved in all aspects of their care,
including pain management

A Team Approach to Implementing the JCAHO

Revised Standards for Pain Management
Others Medical
Nursing
Pharmacy
Managers Dietetic
Rehabilitation
Characteristics of Acute, Chronic,

and Peripheral Neuropathic Pain
Characteristics of Acute Pain
• Sudden, sharp, intense, localized

• Usually self-limited
• May be associated with physiologic changes, eg,
sweating, ↑ HR, ↑ BP
Siddall PJ, et al. In: Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia and
Management of Pain; 1998:675–713.
Characteristics of Chronic Pain
• Gnawing, aching, diffuse

• No definite beginning or end
• Varies in intensity; may remit briefly
• Associated with psychological and social difficulties
• Acute pain may be superimposed
Siddall PJ, et al. In: Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia and
Management of Pain; 1998:675–713.
Characteristics of Peripheral Neuropathic Pain
• Caused by pathologic changes in peripheral nerves

• Spontaneous pain
• Burning, tingling, numbness
• Allodynia, hyperalgesia
Rathmell JP. Katz JA. In: Benzon H, et al, eds. Essentials of Pain Medicine and Regional Anesthesia;
1999:288–294.
Assessment of Pain and Pain Relief

Patient’s Perception of Pain
Pain is subjective and may be influenced by:

• Age1,2
• Gender1
• Culture2
• Communication/language skills
• Previous experience
1. Burns JW, et al. Anaesthesia. 1989;44:2–6.

2. Preble L, Sinatra R. In: Sinatra RS, et al, eds. Acute Pain Mechanisms and Management. St. Louis:
Mosby-Year Book; 1992:140–150.
Benefits of Patient Preparation
• Less postoperative pain1

• Fewer postoperative analgesic medications
• Reduced hospitalization2
1. Croog SH, et al. J Am Dent Assoc. 1994;125:1353–1359.

2. Boeke S, et al. Pain. 1991;45:293–297.
Example of Measurement Tool for Assessing Pain

Visual Analog Scale (VAS)
No pain Pain as bad as it could possibly be
Carr DB, et al. AHCPR Pub. No. 92–0032. 1992.

Frequency of Pain Assessment

and Documentation
• Preoperatively
• Routinely at regular intervals postoperatively
• With each new report of pain
• At suitable intervals after each analgesic intervention
Carr DB, et al. AHCPR Pub. No. 92-0032. 1992.

Pain Mechanisms
The Somatosensory System

Somatosensory
cortex
Frontal
cortex Thalamus
Hypothalamus
Descending
pathway Ascending tracts
Periaqueductal
gray matter Midbrain
Medulla
Dorsal horn area Spinal cord
Noxious stimuli activate receptors in periphery

Peripheral Sensitization
Cell Damage Inflammation Sympathetic

Terminals
Release of pain and inflammatory mediators

eg, bradykinin, H+, prostaglandins
High Threshold Nociceptor

• Central
sensitization
Low Threshold • Hyperalgesia
• Allodynia
Spinal cord
Central Sensitization
Peripheral
Sensitization Tissue Injury
• ↑ C-fiber output
• Hyperalgesia (1°, 2°)
• Allodynia
• Activation of NMDA
receptors
Spinal cord
Hyperalgesia
Primary
• Sensitization of primary neurons → ↓ threshold to noxious stimuli within site
of injury
• May include response to innocuous stimuli
• ↑ pain from suprathreshold stimuli
• Spontaneous pain
Secondary
• Sensitization of primary neurons in surrounding uninjured areas
• May involve:
– Peripheral sensitization
– Central sensitization
Raja SN, et al. In: Wall PB, Melzack R, eds. Textbook of Pain. 4th ed; 1999:11–57.
Allodynia
• Pain evoked by innocuous stimuli
• Central sensitization → pain produced by Aβ fibers1
• Possibly mediated by spinal NMDA receptors2
1. Woolf CJ. Drugs. 1994;47(suppl 5):1–9.

2. Dolan S, Nolan AM. Neuroreport. 1999;10(3):449–452.
Pain Mediators
Cell Damage
Brain
Aa K+ BK
PG
Nociceptor
Spinal cord
HISTAMINE
Mast Cell
Peptides, eg, SUBSTANCE P
SEROTONIN
Platelet
Aa = arachidonic acid; BK = bradykinin; PG = prostaglandin
Role of Neurotransmitters
Excitatory
• Glutamate, aspartate, ATP
• Mediate afferent synaptic transmission
Inhibitory
• GABA, glycine, norepinephrine, 5-HT, adenosine, Ach
• Analgesia at spinal and higher levels
• Altered function → hyperalgesia, neuropathic or chronic
pain
GABA = γ -aminobutyric acid; 5-HT = 5-hydroxytryptamine (serotonin); Ach = acetylcholine

Dougherty PM, Raja SN. In: Benzon HT, et al, eds. Essentials of Pain Medicine and Regional Anesthesia;
1999:7–9.
Role of Neuropeptides
Excitatory
• Substance P, neurokinin A
• ↑ Ca2+, induce sensitization, hyperalgesia
• Transsynaptic transmitters
Inhibitory
• Somatostatin, enkephalins, endorphins, dynorphins (?)
• Modulate intracellular cAMP, K+
• Act at µ , δ , κ opioid receptors
cAMP = cyclic adenosine monophosphate

Dougherty PM, Raja SN. In: Benzon HT, et al, eds. Essentials of Pain Medicine and Regional Anesthesia;
1999:7–9.
Role of Prostanoids in Pain

Prostanoid Production by Cyclooxygenase (COX)
Arachidonic acid
Cyclooxygenase activity of COX
PGG2
Peroxidase activity of COX
PGH2
PGD2 PGF2 PGE2 PGI2 TXA2

α
PG = prostaglandin; TX = thromboxane
Prostanoids and Their Physiologic Activities

Prostanoid
PGE2 Activities/Properties
• Produced in many organs, (eg, kidney,
intestinal tract)
• GI mucosal protection/repair
• Vasodilates
• Diuresis and natriuresis
• Inhibits inflammatory/ allergic cells
• ↑ platelet activation
• ↑ intravascular platelet aggregation
Thromboxane A2
• ↑ smooth muscle contraction in arteries and bronchi
• ↓ platelet aggregation
• Vasodilates
• ↑ renin release in kidney
Prostacyclin (PGI2)
Treatment Options for Acute Pain

WHO Analgesic Ladder

Fre
ed
Op can om fr
ioid ce om
to s for m r pain
± N evere oder
a
± Aon-op pain te
dju ioid
van
Pa
in
t 3
Op or pers
ioid inc i
for rea sting
mo m sin
d i l g
± N erat d to
e
± Aon-o pain
p
dj u i oi d
Pa van
in t
or p e
inc rsis 2
rea tin
sin g
No g
± n-op
Ad i
juv oid
an
t
World Health Organization, 1990. Used with permission.

Analgesic Options for Acute Pain Management
• Opioid analgesics
• Nonopioid analgesics
– acetaminophen
– tramadol
– anti-inflammatory agents
• Combination analgesic products
• Local anesthetics, nerve, neuraxial blocks
Opioid Analgesics
• Binding at µ , δ , κ receptors
• Highly efficacious
• May be combined with anti-inflammatory agents
• Effects may be reversed
• Side effects common
• Pain recurrence
Fishman SM, Borsook D. In: Benzon HT, et al, eds. Essentials of Pain Medicine and Regional
Anesthesia; 1999:51–54.
Adverse Effects of Opioids
• CNS depression, sedation

• Respiratory depression
• ↓ GI motility, nausea, vomiting
• Urinary retention
• Pruritus
Nonopioid Analgesics
Acetaminophen Tramadol
Mechanism ↑ pain threshold • µ -receptor binding

of action • inhibits re-uptake of
norepinephrine and
serotonin (5-HT3)
Adverse effects Hepatotoxic Opioid-like effects
Sisson CB. In: Benzon HT, et al, eds. Essentials of Pain Medicine and Regional Anesthesia; 1999:59–62.
Anti-inflammatory Agents
• Inhibit cyclooxygenase (COX), key enzyme in prostaglandin
synthesis
• Conventional anti-inflammatory analgesics inhibit both COX-
1 and COX-2 isoenzymes
• COX-1 inhibition → gastrotoxicity, ↓ platelet aggregation
• Some newer agents target COX-2 but do not inhibit COX-1 at
full therapeutic doses (specific cox-2 inhibitor, the COXIBS,
e.g. Celecoxib, the savest anti inflamatory agents in this
decade, that effective also as pain killer).
Combination Analgesic Products
• Usually two or more agents with different yet

complementary mechanisms of action
• Severity of dose-related side effects may be reduced,
since lower doses of each agent are utilized
• Range of side effects increased
Local Anesthetics, Nerve, Neuraxial Blocks
• Na+ channel blockade

• Possible interaction at pre- and postsynaptic junctions
• Tachyphylaxis
• Dose-related CNS, cardiovascular toxicity
Nonpharmacologic Treatment Options for Pain

Cognitive-Behavioral
• Relaxation
• Preparatory information
• Imagery
• Hypnosis
• Biofeedback
Physical Agents
• Application of superficial heat and cold
• Massage
• Exercise
• Immobilization (eg, to provide rest and maintain
alignment after musculoskeletal procedures)
• Electroanalgesia (eg, TENS)
• Chiropractic
• Acupuncture
Carr DB, et al. AHCPR Pub. No. 92-0032. 1992.

Other Approaches
Multimodal Analgesia
An Example
Morphine
• Reduced doses of each
analgesic
• Improved antinociception due
to synergistic/additive effects
Potentiation
• May reduce severity of side
effects of each drug
NSAID,
acetaminophen,
nerve blocks
Kehlet H, Dahl JB. Anesth Analg. 1993;77:1048–1056.

New Approaches to Treatment of Acute Pain
• Bradykinin receptor antagonist

• COX-2 specific inhibition
• Cytokine suppressive anti-inflammatory agents
(CSAIDs)
• Neuropeptide inhibitors
• Epibatidine analogues
Rang HP, Urban L. Br J Anaesth. 1995;75(2):145–156.

Acute Pain Services

Management of Surgical Pain

The Unmet Needs
• Pain is undertreated
• Inadequate knowledge of pain management
• Inadequate pain assessment
Rawal N. Anesth Pain Med. 1999;24(1):68–73.

Sinatra R. In: Cousins MJ, Bridenbaugh PO. Neural Blockade in Clinical Anesthesia and Management of
Pain; 1998:793–835.
American Pain Society Quality Improvement Committee. JAMA. 1995;1847–1880.
Acute Pain Services

Goals
• Improve management of surgical pain
• Promote continuing education and training of healthcare
providers
• Increase awareness of importance of effective pain
management
• Serve as clinical research center
Chin ML. In: Ashburn MA, Rice LJ, eds. The Management of Pain; 1998:537–545.

Acute Pain: Mechanisms, Management, and Treatment Options

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Acute Pain: Mechanisms, Management, and Treatment Options

Definition and Features

“Pain is an unpleasant sensory and emotional experience

International Association for the Study of Pain. Pain. 1979;6:249.

Features of Acute Pain

Physiologic Consequences of Acute Pain

Physiologic Consequences of Acute Pain

Bonica JJ. The Management of Pain. 2nd ed. Vol. 1; 1990.

General Stress Response

ACTH = adrenocorticotropic horrmone

↓ Tidal ↓ Vital ↓ FRC ↓ Alveolar ↓ Mobility

FRC = functional residual capacity; V/Q = ratio ventilation:perfusion of the lung

Respiratory Effects (Cont’d)

Lobular collapse Hypoxemia

↑ Anxiety, pain ↑ HR, ↑ PVR, ↑ BP, ↑ cardiac output

MI = myocardial infarction; HR = heart rate; PVR = peripheral vascular resistance; BP = blood

Effects on Peripheral Circulation

↓ Limb blood flow1

Gastrointestinal and Urinary Effects

Musculoskeletal Effects (Cont’d)

Effects on Pain-Signaling Systems

↑ Peripheral nociception ↑ Nerve excitability

• Hyperalgesia (1° + 2°)

Chronic pain Damaged spinal

Other Effects of Acute Pain

Drucker W, et al. J Trauma. 1996;40(3):S116–122.

Advantages of Effective Pain Management

• Patient comfort and satisfaction1,2,3

1. Eisenach JC, et al. Anesthesiology. 1988;68:444–448.

JCAHO and Pain Management

Joint Commission on Accreditation

• New standards in 2000–2001; scoring begins in 2001

Joint Commission on Accreditation of Healthcare Organizations. Jt Comm Perspect. 1999;19(5):6–8.

Pain: The Fifth Vital Sign

• Pain should be considered the “fifth vital sign”

American Pain Society Quality Improvement Committee. JAMA. 1995;1847–1880.

JCAHO Revised Standards: The Patient’s Rights

• Patients have the right to appropriate assessment and

Joint Commission on Accreditation of Healthcare Organizations. Jt Comm Perspect. 1999;19(5):6–8.

A Team Approach to Implementing the JCAHO

Characteristics of Acute, Chronic,

Characteristics of Acute Pain

• Sudden, sharp, intense, localized

Characteristics of Chronic Pain

• Gnawing, aching, diffuse

Characteristics of Peripheral Neuropathic Pain

• Caused by pathologic changes in peripheral nerves

Assessment of Pain and Pain Relief

Patient’s Perception of Pain

Pain is subjective and may be influenced by:

1. Burns JW, et al. Anaesthesia. 1989;44:2–6.

Benefits of Patient Preparation

• Less postoperative pain1

1. Croog SH, et al. J Am Dent Assoc. 1994;125:1353–1359.

Example of Measurement Tool for Assessing Pain

No pain Pain as bad as it could possibly be

Carr DB, et al. AHCPR Pub. No. 92–0032. 1992.

Frequency of Pain Assessment

Carr DB, et al. AHCPR Pub. No. 92-0032. 1992.

The Somatosensory System

Dorsal horn area Spinal cord

Noxious stimuli activate receptors in periphery