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Progress in biomedical science has advanced our understanding of chronic pain



Though the magnitude of the problem is clear, many people are unfamiliar with the underlying drivers of chronic pain. Research has shown that several biochemical mediators, including prostaglandins, cytokines (TNFα, IL-1ß, IL-6), chemokines (CCL2, CXCL1, CXCL5), growth factors (NGF, BDNF), and neuropeptides (substance P, CGRP) play a key role in the pain pathway and in making chronic pain chronic.1-3

CCL2=C-C motif chemokine ligand 2; CGRP=calcitonin gene-related peptide; CV=cardiovascular; CXCL=C-X-C motif chemokine ligand; IL=interleukin; TNF=tumor necrosis factor.

Acute vs Chronic Pain:
Explore the Pain Pathway

Chronic pain is physiologically different from acute pain.1,6 Follow the pain signal through the pain pathway from the periphery to the central nervous system (CNS) to learn more about the role that different mediators, including prostaglandins, cytokines, and NGF,  play in chronic pain.

See Chronic Pain in Action

Gain a deeper understanding of the different mediators that contribute to chronic pain.

Throughout the world, 1 in 5 people suffer from moderate to severe chronic pain.

Chronic pain can have a significant negative impact on those afflicted, with effects including sleeplessness, decreased activity, and mood changes such as depression.

Acute pain and chronic pain can have different pathophysiologies.

In acute pain, nociceptors – pain receptors in peripheral nerves – are activated when the body experiences injury or inflammation.

The nerves in the periphery send pain signals through the dorsal root ganglia to the spinal cord and central nervous system, or CNS.

When pain is acute, signaling typically stops once the cause of pain is resolved.

However, when pain is chronic—lasting more than 3 months—repeated stimulation of these sensory nerves over time causes changes to the ways the pain signals are processed,

leading to a pathophysiological state where the nervous system is sensitized and the perception of pain becomes heightened.

Both the peripheral and the central nervous systems can become sensitized to pain signals.

In response to injury or inflammation, nociceptors in the periphery can become more sensitive to painful stimuli—a process called peripheral sensitization.

These sensitized nociceptors then send additional pain signals to the CNS, which can lead to the overstimulation of the CNS.

This results in central sensitization, which increases the perception of pain. As such, central sensitization leads to the perpetuation of pain.

In response to injury or inflammation, cells at the site of pain release a variety of biochemical mediators, including the neurotrophin NGF, the cytokine TNFα, the interleukins IL-1ß and IL-6, and prostaglandin E2.

These mediators bind to nociceptors in the periphery, leading to the sensitization of the pain pathway.

When the cause of pain continues over time, the persistent activation of the pain pathway leads to increased synthesis of glutamate and neuropeptides, such as Substance P, CGRP, and BDNF.

Substance P and CGRP enhance the sensitization of sensory nerves in the periphery. In the CNS, all 4 of these mediators can be released by the primary afferent neuron, subsequently binding to receptors in the dorsal horn of the spinal cord, contributing to the activation of key intracellular pathways that initiate central sensitization.

In conditions with features of chronic pain, such as osteoarthritis, ……rheumatoid arthritis……gout……or chronic low back pain, increased levels of neurotrophins and pain mediators can lead to the sensitization of nerves in both the peripheral and the central nervous system. 

Peripheral and central sensitisation can result in a heightened perception of pain. Such chronic pain can be difficult to manage effectively, but if inadequately controlled it could affect or restrict patient’s daily mobility and functioning….routine tasks… or domestic activities and hobbies.

Chronic pain can therefore have “ripple effects” beyond the patient themselves, for example on their family relationships.

In summary, peripheral and central sensitisation are important factors that can help us understand more about the management of chronic pain.  What happens here…

… changes what happens here.

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