Accurate Education – Pain Anatomy and Physiology

Pain – Anatomy and Physiology



Understanding Pain:

Neurobiology of Pain


Neuropathic (Nerve) Pain

Central Sensitization

Pain Definitions and Terms


Key to Links:

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“The whole purpose of education is to turn mirrors into windows.”

 – Sydney Harris


Pain Anatomy and Physiology

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Pain Pathways:

The following is largely taken from:

“Role of buprenorphine in acute postoperative pain”

J. Alcázar-Castro, O. Carrillo-Torres∗, P. González-Navarro Anaesthesiology Department, ‘‘Eduardo Liceaga’’

General Hospital of Mexico, Mexico City, Mexico June 2016



 The Pain Train

After pain receptors called nociceptors are stimulated by trauma or injury, primary mediators such as prostaglandins, leukotrienes, serotonin, and bradykinins are released from the nociceptors. These primary mediators stimulate the release of peptides such as calcitonin gene-related peptide (CGRP) and substance P from inflammatory cells including mast cells at the site of injury. Vasodilation is induced by histamine, the release of nerve growth factor, and the sympathetic effect reflex release of norepinephrine, known as ‘‘inflammatory soup.’’


The peripheral nociceptor impulses travel through delta and C synapse fibres in laminae II and V in the spinal cord. The C fibres also make synapses in spinal cord lamina I, known as second order neurons. There are two types of second order neurons in the spinal cord: the first, in lamina I, respond to impulses in the C fibres; the second, located in lamina V, respond to both harmful stimuli, mainly from A-delta fibers, and non- harmful stimuli. Neurotransmitters such as glutamate and aspartate present in lamina V cause fast synaptic transmission. This happens by binding to and activating kainate receptors (KAR), receptors regulating Na+ and K+, the influx of ions, and amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Both AMPA and KAR are nearly impermeable to Ca+ ions. Once the AMPA and KAR receptors are activated, NMDA priming begins.


The N-methyl-d-aspartate (NMDA) receptors are located post-synaptically in the posterior horn of the spinal cord. They are responsible for mediating the reaction caused by polysynaptic discharge of the primary nociceptive afferent fibers. Activating these NMDA receptors is related with transmission in nociceptive afferent fibres, possibly A-delta and C fibers.


The NMDA receptors are associated with learning and memory, neural development and plasticity, as well as states of acute and chronic pain. They intervene in initiating and maintaining central sensitisation, associated with damage or inflammation to peripheral tissues.


As for modulation, endogenous and exogenous opioids can act on the presynaptic terminals of primary afferent nociceptors via the mu opioid receptor which indirectly blocks the calcium channels and opens the potassium channels. Inhibiting calcium from entering the presynaptic terminals and releasing potassium results in hyperpolarisation and inhibits the release of pain neurotransmitters, and therefore in analgesia.


Activation of the cortical descending neural pathways involves releasing neurotransmitters: beta-endorphins, enkephalins, dynorphins. These peptides modulate pain, even in stressful situations. The activation of the descending pathways by endorphins takes place through specific receptors: opioids. This system is activated around the periaqueductal grey matter of the midbrain. These neurons are projected to the medullary reticular formation and the locus coeruleus where serotonin and norepinephrine are produced, respectively. The descending fibers are then projected to the dorsolateral funiculus of the spinal cord dorsal horn for synapsis with the primary afferent neuron.


The descending pain modulating neurons play the role of releasing neurotransmitters in the spinal cord, such as serotonin and norepinephrine. They activate interneurons that release opioids in the spinal dorsal horn. Releasing serotonin and norepinephrine inhibits the release of pain transmitters in the nociceptive afferent signals and inhibits cellular second order pain transmission. Administering opioids activates the opioid receptors in the midbrain. Moreover, activating the opioid receptors in the second order pain transmission cells prevents ascending transmission of the pain signal, activating the opioid receptors in the C fibre central terminals in the spinal cord prevents the release of pain neurotransmitters, and activating the peripheral opioid receptors inhibits the activation of nociceptors and inhibits the cells that release inflammatory mediators.

Role of buprenorphine in acute postoperative pain – 2016

Emphasis on Education


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