The perception of pain

Ching-Liang Lu

What is pain?

• Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage

IASP – International Association for the Study of Pain 2009

What is pain?• Pain is

– subjective

• not a stimulus, but an experience

– protective (acute)

– modified by developmental, behavioural, personality and cultural factors

• Associated signs are crying, sweating, increased heart rate, blood pressure, behavioural changes etc

Pain

• Dimensions of the ‘PAIN”

– Sensory-discriminative

– Affective-motivate

– Cognitive

Nociceptive vs Neuropathic PainNociceptive

PainCaused by activity in

response to potentially tissue-damaging stimuli

Neuropathic Pain

Initiated or caused by primary lesion or dysfunction in the nervous system

Pospostoperative

pain

toperativepain

Mechanicallow arthritis, back pain

Sickle cellcrisis

Arthritis

Postherpeticneuralgia

Neuropathic low back pain

Phantom pain

Sports/e sports or exercise injuries xerciseinjuries

*Complex regional pain syndrome

Central post-stroke pain

Trigeminalneuralgia

Distalpolyneuropathy

(eg, diabetic, HIV)

Nociceptive pain: Tissue injury/inflammation

Postherpetic neuralgia

Acute vs Chronic Pain

Characteristic Acute Pain Chronic Pain

Cause Generally known Often unknown

Duration of pain Short,

well-characterized

Persists after healing,

3 months

Treatment

approach

Resolution of

underlying cause,

usually self-limited

Underlying cause and pain

disorder; outcome is often

pain control, not cure

What is Acute Pain?

• Physiologic response to tissue damage

• Warning signals damage/danger

• Helps locate problem source

• Has biologic value as a symptom

• Responds to traditional medical model

• Life temporarily disrupted (self limiting)

Acute pain is not that bad.

What is Chronic Pain?

• Chronic pain is persistent or recurrent pain, lasting beyond the usual course of acute illness or injury, or more than 3 - 6 months, and adversely affecting the patient’s well-being

• Pain that continues when it should not

Domains of Chronic Pain

Social Consequences

• Marital/family relations

• Intimacy/sexual activity

• Social isolation

Socioeconomic

Consequences

• Healthcare costs

• Disability

• Lost workdays

Quality of LifePhysical functioningAbility to perform

activities of daily living

WorkRecreation

Psychological MorbidityDepressionAnxiety, angerSleep disturbancesLoss of self-esteem

Pain measurement

Nociceptors

• 3 classes of nociceptors

–Mechanical: pinch, punctate, squeeze

–Thermal: above 45C or below 5C

–Polymodal: mechanical, thermal, chemical

Somatic receptor types

Thermosensation

HeatDRG • 45% small- to medium-diameter neurons: threshold of ∼42°C heat-sensitive C and type II Aδ fibres TRPV-1 receptor• 5-10% medium- to large-diameter cells: threshold of ∼51°C type I Aδ TRPV-2 receptor• TRPV-3 TRPV -4: warm range 31∼39°C

Thermosensation

Cold•TPRVM8 receptor: ∼26°C ; (cool to cold) express

in 10-20 % of small-diameter neuron• TRPA1: ∼17°C painful cold ?

TRP channel family

AFFERENT (SENSORY) NEURON

Nociceptive afferents

Compound Action Potential

First pain: Sharp, faster A-delta fibers

Second pain: Dull, slower C-fibers

Blocking each nerve blocks the sensation

Anita

註解

進入背根 隻候影響MOTOR

Referred pain

• Signals from muscles and viscera can be felt as pain elsewhere

• Example: myocardial infarction and angina can be felt in chest and left arm

• Mechanism: convergence of afferents muscle/ viscera afferents and somatic afferents.

• Convergence on the same projection neurons in the dorsal horn

• The brain cannot tell the difference

Neurotransmitters

• Excitatory neurotransmitters:glutamate, tachykinins

calcitonin gene-related peptide, vasoactive intestinal polypeptide, .

• Inhibitory neurotransmitters:gamma amino butyric acid (GABA)

• Neurotransmitters involved in Descending Pain Regulation:noradrenaline (norepinephrine)

serotonin

Opiates

Substance P in dorsal horn

Pain modulation below spinal level

1. PERIPHERAL

2. CENTRAL

1. Peripheral (Sensitization)

TISSUE INJURY

RELEASE OF SUBBSTANCE-P CHEMICAL MEDIATORS OF

AND GLUTAMATE INFLAMMATION

STIMULATE NOCICEPTORS IN

THE PERIPHERY

Peripheral Sensitization

NSAID

Peripheral sensitization

53C 30 sec at site A&D

• “Wind-up”

– Response to second stimulus is stronger than the response to the first one in C fiber

• Change in temporal integration

Central sensitization for chronic pain:

wind-up

40

30

20

10

0

0 10 20

ControlNMDA antagonist

Stimulus number

"Wind-up" is NMDA mediated. Response with and without an NMDA antagonist.

Ascending pathwaysSpinal cord ThalamusCortex

New pathway for visceral pain:

Dorsal column pathway

Brain Pain perception

Rene Descartes (1596-1650)

No Brain, No Pain

Lateral system: S1/2Discrimitive component

Thalamus

Medial system:Affective component

Neuroimaging of acute painMuscle pain

Visceral pain

Niddam et al., 2002

Insula

Amygdala

ACC

PCC

Vermis

Thalamus

PPC

PFC

ACC

PCC

PCC

Vermis

PFC

PPC

PFC

Insula Insula

Lu et al., 2004

Chen et al.

Lin et al. (preliminary)

Tooth pain

Cutaneous pain

Cortical neuronal correlates upon balloon distension in GI tract (volunteers)

Aziz Q. Gastroenerology 1997; 113:50

Lu CL Neurogastroenterol 2004;16:575Gastroenerology 2005; 128:1529

Esophagus Rectum Antrum Fundus

Mertz H. Gastroenerology2000; 118:8342

Ladabaum U. Gastroenerology 2001; 120:369

Pain modulation (inhibition)

• Gate control theory

• Descending inhibition

Gate control theory• P.D. Wall & R. Melzack (1965)

• “There is an interaction between pain fibres and touch fibre input at the spinal cord level in the form of a ‘gating mechanism’

Aβ fibres

Aδ, C fibres

Gate control theory

When pain fibre is stimulated, gate will be opened & pain is felt

pain

pain is felt

+

gate is opened

Gate control theory

When pain and touch fibres are stimulated together, gate will be closed & pain is not felt

pain is not felt

gate is closed

TOUCH

PAIN

Gate control theory• This theory provided basis for various

methods of pain relief

– Massaging a painful area

– Applying irritable substances to a painful area (counter-irritation)

– Transcutaneous Electrical Nerve Stimulation (TENS)

– Acupuncture ?

Descending inhibition

• Direct stimulation of PAG produces analgesia

– Inhibits firing of nociceptive neurons in lamina I and V

– Descending pathway recruited: PAG excites rostroventral medulla/nucleus raphe

magnus (5HT); Locus Ceruleus(NE)

• Role of Opioid receptor

– Opioid-induced analgesia via endogenous opioid receptors (-, δ-, κ-) in descending pathway (PAG, ventral medulla, superficial dorsal horn)

– Endogenous opioid peptide: enkephalins, β-endorphin, dynorphin

– Stress-Induced Analgesia (SIA)

Key points

• The pain experienced by patients is a result of the interaction between sensory and emotional experiences.

• Afferent fibers– Aδ fibres transmit rapid, sharp, localized pain. – C fibres transmit slow, diffuse, dull pain.

• Ascending pathway– Spinothalamic, spinoreticular, spinomesencephalic tracts

• Pain modulation – Gate control at dorsal horn of the spinal cord – Descending inhibitory pathways.