Chapter 27 Preemptive Analgesia Flashcards Preview

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Flashcards in Chapter 27 Preemptive Analgesia Deck (19):

Preemptive analgesia

an analgesic (antinociceptive) treatment that prevents the transmission of noxious afferent input to the central nervous system and/ or development of altered processing of the afferent input
that amplifies postoperative pain


Preventive analgesia

an antinociceptive treatment encompassing the entire period of highintensity noxious stimuli produced by the peripheral nervous system that can alter peripheral or central sensory processing.


Two Phases of Preventive analgesia

the primary phase during which the noxious stimuli is related to the surgical
injury itself; and the secondary phase during which the
ongoing noxious stimuli is produced by the release of
chemicals, including inflammatory mediators from damaged tissue. The secondary phase can begin duringthe intraoperative period and extend long into the postoperative recovery period.


peripheral and central sensitization

tissue injury resulting
from a noxious stimulus produces changes in the peripheral afferent and in the spinal cord, which leads to prolonged excitability. This hypersensitive state can persist for days to months, and contributes to acute and chronic postsurgical pain, a process referred to as peripheral and central


Peripheral sensitization

following tissue injury, a multitude of inflammatory
mediators are released and activate the peripheral
nociceptive afferent. The continued activation of these
afferents enhances the patient’s response to further stimuli. The inflammatory mediators can activate and increase the sensitivity of the nociceptors, thereby changing the nociceptive threshold of the afferent. Persistent activation can also lead to alterations in the neurophysiologic properties
of the primary afferent itself. Peripheral sensitization refers
to the summation of these processes.


Transient receptor potential vanilloid (TRPV) receptors

on small C-fibers are nonselective cation channels. TRPV receptors are known to play an important role in peripheral sensitization and, thus, are prime targets for novel analgesics. They are activated by repeated heat stimulation or exposure to acidic environments found in healing
tissues, which results in a painful burning sensation


Inflammatory mediators

prostaglandin E2, serotonin,
bradykinin, epinephrine, adenosine triphosphate,
interleukin-1b, interleukin-6, tumor necrosis factor, chemokines, and nerve growth factor, also sensitize TRPV


sensory neuron-specific sodium channels and TRPV
receptors can be phosphorylated by intracellular kinases (protein kinase C or tyrosine kinase), thereby potentiating

the release of excitatory amino acids and peptides from
sensory afferents and accentuating the pain.


The inflammatory
activation of TRPV receptors and sensory neuronspecific
sodium channels results in

vasodilatation and edema.


The neurogenic inflammation is mediated by

a calcitonin gene-related peptide, substance P, and neurokinin A, and can further sensitize the nociceptive afferents, leading to allodynia or hyperalgesia


Hypersensitivity and alterations that take place in the central nervous system, the spinal cord, and supraspinal structures as a result of a surgical injury

Following a tissue
injury, such as an incision through the skin fascia and
muscle, a subset of Ad- and C-fibers becomes spontaneously active,5 and barrages the second-order neurons in the
spinal cord. In turn, these neurons release excitatory neurotransmitters,
which increase the amplitude of the spinal cord neuron response and lower the response threshold
for further stimuli


the response of the dorsal
horn neurons to a particular stimulus

stimulus—be it noxious (hyperalgesia) and/or innocuous (allodynia)—is altered, and perception of the painful stimulus is increased in intensity
as well as duration


injury results in alterations of
dorsal horn neurons

neurons react to non-noxious
stimuli as if they were noxious (allodynia) and to noxious
stimuli (hyperalgesia) with an exaggerated response, but
they also begin to respond to stimuli outside their original
receptive field (secondary sites)


Central sensitization has two temporally distinct phases.

An early phase of hypersensitivity is triggered by changes in glutamate receptor phosphorylation and ion channel properties. The second phase (longer lasting) involves transcriptional changes that result in formation of new proteins
responsible for prolonged pain hypersensitivity



NMDA antagonist, Its major benefit is probably related to its
modulation of opioid-induced hyperalgesia. A decrease in
opioid-induced hyperalgesia has been associated with
lower postoperative pain scores and opioid consumption.


One class of oral medications that appears to have
a potential for inducing preemptive and preventive analgesia

gabapentinoids, gabapentin and


gabapentin and pregabalin side effects

cause postoperative
sedation or drowsiness


central sensitization and
persistent pain after surgical incision is predominantly maintained by

the incoming barrage of sensitized peripheral
pain fibers throughout the perioperative period27 and
extending into the postsurgical recovery period.



surgical incision does not produce a single, one-time noxious stimulus, but a continuous barrage of C-fiber and Ad-fiber input to the spinal cord. Hence, a single, preincisional analgesic intervention is not likely to block this assault throughout the postsurgical recovery period, thereby allowing nociceptive information to reach the spinal cord and resulting in hypersensitization. Likewise, the inflammatory
processes incited by the surgical incision also produce
central sensitization for a prolonged period following surgery

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