Pain Pathophysiology Overview - Peripheral Sensitization - Central Sensitization - Gate Control Theory of Pain

1. PAIN PATHOPHYSIOLOGY
AN OVERVIEW
Ade Wijaya, MD – December 2019

2. IASP Definition of Pain
◦ Pain
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or
described in terms of such damage.

5. Peripheral Sensitization
Peripheral sensitization indicates increased responsiveness and reduced threshold of nociceptive neurons in the
periphery to the stimulation, which usually occurs after peripheral tissue injury and inflammation
Si-Qi Wei, Zhuo-Ying Tao, Yang Xue and Dong-Yuan Cao (December 4th 2019). Peripheral Sensitization [Online First], IntechOpen

6. Peripheral sensitization
Tissue
irritation
Release
inflammatory
mediators
 Nociceptor
threshold
Allodinia
Hyperalgeusia
Recruitment of so-called silent nociceptors, which are not usually sensitive to painful stimuli or
inflammatory substrates such as prostaglandins or bradykinin.

7. Mechanism
◦ (1) early post-translational changes in the peripheral terminals of nociceptors, for example, the
phosphorylation of the ion channels prolongs depolarization and enhances response by lowering the open
threshold or prolonging the open time of channels;
◦ (2) altered gene expression, changing transcription or translation of certain protein. For instance, deletion or
silencing of calcitonin gene-related peptide alpha (αCGRP) gene expression drastically reduces TRPV1
potentiation in peptidergic nociceptors by abrogating its Ca2+-dependent exocytotic recruitment.
Si-Qi Wei, Zhuo-Ying Tao, Yang Xue and Dong-Yuan Cao (December 4th 2019). Peripheral Sensitization [Online First], IntechOpen

9. Central Sensitization
A condition of the nervous system that is associated with the development and maintenance of chronic pain
A change in functional state of neurons and nociceptive pathways throughout the neuraxis, caused by increased
membrane excitability and synaptic efficiency or by decreased inhibition on this system
Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature. 1983;306(5944):686-8.

10. Mechanism
◦ NEURONAL SENSITIZATION
◦ REDUCTION IN INHIBITORY INTERNEURON ACTIVITY
◦ MODULATION BY DESCENDING PATHWAYS

12. ◦ Intense electrical or noxious stimulation of C fibers can promote wide-dynamic-range (WDR) neuron
hyperexcitability in the dorsal horn
◦ Molecular mechanism of WDR: excitatory amino acids, tachykinins, and calcitonin gene–related peptide
(CGRP)
◦ These transmitters and neuromodulators affect dorsal horn neuron activity by directly increasing cation
fluxes, impinging on intracellular transduction mechanisms, and modulating receptor and transmitter gene
transcription.
◦ Synaptic transmission augmentation at NMDA receptors is the final common pathway

14. MODULATION BY DESCENDING
PATHWAYS

18. THANK YOU