Nociception and Pain Modulation

Dr Sadia Fatima
 Objectives
• Define Pain, Sensitization, Hyperalgesia and
Allodynia
• Classify pain based on different modalities
• Discuss nociceptor (TRPV) and factors
affecting it
 Pain: Definition
• An unpleasant sensory and emotional experience
associated with actual or potential tissue damage.

• Pain is whatever the experiencing person says it is.

• May not be directly proportional to amount of tissue

injury.

• Highly subjective, leading to under treatment

 Major Categories of Pain

Duration Speed

First/ Second/
Acute Chronic Fast Slow

Character Nature

Localized Diffuse Nociceptive Neuropathic

• Somatic • Nerve
• Visceral • Nervous system

Mechanical, Thermal, Chemical

Nociceptors [Hurt]
Noxious stimuli
 Classification of nerve fibers

• A delta= Glutamate • C= Substance P

• Skin
• Mechanical (pressure, Type I Aδ)
• Thermal (menthol and cold / capsaicin
and hot) (>45 <5°C) Type II Aδ)
• Responsive to analgesic
• Deep tissue, Viscera and Skin
• Polymodal- Silent Nociceptors
(high intensity all modalities)
• Nonresponsive to analgesic
If you hit your thumb with a hammer,
what will happen?
Transient receptor Potential (TRP) channel or
Capsaicin or Vanilloid receptor

• Resemble Voltage gated Na or K

channels
• 6 transmembrane domain with a
pore between domain 5 and 6
• Closed at rest
• TRPV1= Capsaicin, heat,
endovanilloids
• TRPV4= Peizo2; environmental
chemical irritants
• ASIC3 (acid sensing ion
channels)= muscle [skeletal and
cardiac]; pH changes due to
ischemia
TRPV1 channel or Capsaicin or Vanilloid receptor

Nav1.7= A delta fibers (Mutations can lead to loss hyperexcitability)

Nav 1.8 = C fibers
Local Anesthetics
Activation of Nociceptors by Noxious Stimulus

National Institute for Physiological Sciences

Nobel Prize in Physiology or Medicine
 Activation of Nociceptors by Chemical Stimulus

Why are Non-steroidal anti-inflammatories, such as ibuprofen, effective in

minimizing pain?
Somatosensory pathways

Classical pathways
Glutamate
AMPA
NMDA

• Spinothalamic
• Spinoreticular
• Spinomesencephalic
• Cervicothalamic
• Spinohypothalamic

From: Møller, 2005

 Somatosensory pathways

Non-classical pathways
Pain pathways

Limbic system Association cortex

SII

"WHAT" "WHERE"
SI cortex

Thalamus
dorsal
Thalamus
ventral

Medial
lemniscus

Reticular formation

AROUSAL

Anterior
lateral tract

Fig 3.3
From: Møller, 2005
 Referred Pain

V, Aδ, Aß, C fibers.

Dynamic range neurons
 The abnormal neural activity that
causes symptoms not generated at the
location where the symptoms are felt
Examples:
• Phantom pain
Gate theory Endogenous Opioids

Descending fibers also

release substances such as
norepinephrine and
serotonin (referred to as
endogenous opioids or
endorphins) which have
the capability of
inhibiting the
transmission of noxious
stimuli.
Questions