“The whole purpose of education is to turn mirrors into windows.”
– Sydney Harris
Pain – Anatomy and Physiology
Understanding Pain:
Key to Links:
Grey text – handout
Red text – another page on this website
Blue text – journal publication
.
Pain Anatomy and Physiology
This page is under construction
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.’’
Stimulation of pain receptors results in depolarization of primary afferent nerve fibers that spreads to the dorsal horn of the spinal cord via 2 pathways. One pathway, corresponding to fast pain, is carried by A-delta fibers and allows for precise localization of a pain source. The signal is carried to the lateral thalamus by the neospinothalamic tract in the spinal cord. From the lateral thalamus, the signals are then transmitted to the sensory cortex (S1 and S2 areas).
The second way of pain transmission is carried by unmyelinated C fibers, responsible for slow and widespread but poorly localized pain . In the brain, pain signaling is carried to the medial thalamus, the limbic structures, the insula, the cingulate cortex, and the frontal cortex. The thalamus is an essential nociceptive (pain) relay, discriminating nociceptive signals and transmitting some of the signals from the spinal cord to the cortex, which triggers the conscious perception of pain sensation. The thalamus can also be influenced by the cortex as well as by the limbic system, where the pain is influenced memory and emotion.
Signals from the brain centers are also integrated in the periaqueductal gray area, which, via the rostral ventromedial medulla, modulates descending nerve pathways to the spinal cord dorsal horn to enhance or inhibit nociceptive input. Via these descending pathways, supraspinal nerve pathways impact the activity of spinal interneurons by releasing various neurotransmitters to modulate nociceptive signals ascending to the brain, exerting enhancing or inhibitory effects on the processing of pain signals.
In this network, mast cells are important gatekeepers of pain. Mast cells located on the brain side of the blood-brain barrier and in the leptomeninges, can interact with neurons, glia cells, microglia, and vascular endothelial cells by transmitting their mediators. Mast cell mediators can effectively spread through brain tissue and since 90% of thalamic histamine and up to 50% of total brain histamine is synthesized by mast cells, mast cells can significantly influence brain functions related to pain.
Neurotransmitters
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.
Emphasis on Education
Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.
For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.
Should you wish more information regarding any of the subjects listed – or not listed – here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.
For more information, please contact Accurate Clinic.
Supplements recommended by Dr. Ehlenberger may be purchased commercially online or at Accurate Clinic.
Please read about our statement regarding the sale of products recommended by Dr. Ehlenberger.
Accurate Supplement Prices
.