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Gharagozloo. Mini-invasive Surg 2020;4:8 I http://dx.doi.org/10.20517/2574-1225.2019.62 Page 3 of 13

Consequently, stimulated nociceptors are upregulated and become more responsive to further stimuli.
Hyperalgesia refers to the phenomenon by which stimulated nociceptors become more sensitive to further
stimuli. In addition to upregulation from the original stimulus, several humoral pathways enhance the
effect of the painful stimulus. Tissue damage, such as with any incision, releases certain mediators, e.g.,
bradykinin, potassium, calcitonin gene-related peptide, and prostanoids such as prostaglandins and
[1]
leukotrienes . Substance P is also released. Substance P acts on mast cells to induce degranulation with the
resultant release of histamine. All these activate and sensitize nociceptors. Substance P also dilates blood
[4]
vessels, causing edema, and releasing more bradykinin . Combination of the humoral mediators results in
a decrease in the activation threshold and enhances the sensitivity of the nociceptors to further stimuli. In
addition, the “cascade” effect results in increased nerve sensitivity over a much wider field than the original
injury.

Understanding the peripheral pathways and the chemical mediators is important in devising techniques
for pain control. For example, peripheral opioid receptors are uncovered in response to inflammation.
These receptors are the target for endogenous opioids, which are released locally by the immune system.
[2]
Binding these opioid receptors acts to decrease nociceptor output . Furthermore, it has been shown that
a second group of nociceptors are stimulated only by inflammation and serve to increase pain perception
after the original tissue damage. Although unrelated to the original stimulus, decreasing inflammation
postoperatively helps to minimize the sensitization of these nociceptors.

Two central components in understanding pain in the postoperative patient are peripheral sensitization
and central sensitization.

Peripheral sensitization occurs as the result of the pathways outlined in the previous discussion. Once
a patient experiences pain, they can have an increased sensitivity to the same stimulus. This results in
hyperalgesia. Allodynia results when a previous stimulus that had at one time not caused pain now
does. New synapses are formed with dorsal horn cells that previously received nociceptive input and
this redistribution allows mechanoreceptors to activate pain pathways by stimuli that are normally non-
[5]
noxious, such as touch .
There is augmentation of the initial pain response after the peripheral nociceptors synapse with second-
order neurons in the dorsal horn of the spinal cord. This is the phenomenon of central sensitization. With
repeated stimulation by painful stimuli, the second-order neurons become hyper-responsive and exhibit
augmented sensitivity. This phenomenon is referred to as “wind up”. Chemical mediators such as excitatory
amino acids glutamate and aspartate at N-methyl-D-aspartate (NMDA) result in central hypersensitivity.
Repeated peripheral stimuli lead to changes in the dorsal horns of the spinal cord or neuroplasticity, which
[6]
contributes to increased hypersensitivity to peripheral stimuli . It is hypothesized that the irreversible
changes which occur in the dorsal horns of the spinal cord in response to repeated peripheral stimuli may
be the cause of chronic pain syndromes.

It is generally accepted that postoperative pain is related to many factors, including the amount of soft
tissue injury, resulting inflammation, and rib injury (as in the case of a thoracis surgical procedure). There
are other individual factors that need to be considered, including, but not limited to, preoperative tolerance
to medications, psychological and social factors, and other co-existing morbidities that may or may not
contribute to pain (an example of this is fibromyalgia).

PAIN AFTER ROBOTIC THORACIC SURGERY
Assessment and treatment of the patient undergoing robotic thoracic surgery should utilize the same
concepts of peripheral and central sensitization as in any patient experiencing pain after thoracic surgery.