Pain syndromes are important to understand as a neurologist as 1 in 10 people in the U.S. suffers from chronic pain! Also, this topic is covered on neurology examinations. Here you will review the pathophysiology of pain with appropriate depth for RITE® and board examinations, and become familiar with the most commonly tested pain syndromes.
Authors: Brian Hanrahan MD, Steven Gangloff MD
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Table of Contents
Pathophysiology of Pain
- Pain perception is both a function of the peripheral and central nervous system via both excitatory and inhibitory pathways.
- Glutamate and substance P are the neurotransmitters most involved in promoting pain sensation, while norepinephrine, serotonin, and endogenous opioids like enkephalin inhibit pain sensation.
Ascending pain pathway
- Noxious stimuli applied to skin → Travels along aδ (fast) and C (slow) nerve fibers within afferent first-order neurons → synapses in substantia gelatinosa (Rexed lamina I and II) within the dorsal horn of spinal cord→ ascends through the tract of Lissauer up 3 spinal levels and decussates to contralateral side → ascends through spinothalamic tract (second-order neuron) → synapses on ventral posterior lateral (VPL) nucleus of thalamus → travels along third-order neurons to the somatosensory cortex.
- Before the thalamus, spinoreticular fibers branch off to the reticular formation and contribute to emotional components of pain.
- While the somatosensory cortex functions to localize pain, the amygdala, insula, anterior cingulate cortex, prefrontal cortex, and thalamus aid in the perception of pain.
Descending (modulatory/inhibitory) pain pathway
- Pain perception is modulated and regulated by fibers within the periaqueductal gray, as well as the locus coeruleus.
- After a pain response is received, fibers from the locus coeruleus descend to transmit norepinephrine back to the dorsal horn to attenuate that pain response.
- The periaqueductal grey (and rostral ventromedial medulla) contain opioid receptors and use the endogenous opioid enkephalin in the descending pathway to blunt pain response.
- Enkephalin inhibits GABA and in turn, allows for serotonin levels to increase.
- Norepinephrine and serotonin function in this descending inhibitory pathway as the main neurotransmitters for pain inhibition.