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Preemptive analgesia as a concept began over 90 years ago, when Crile
and Lower proposed that blocking noxious signals prior to a surgical
incision may lead to some degree of central nervous system (CNS) protection
against postoperative pain, though at that time the mechanism remained
unclear.1 Crile believed that a combination of
locoregional blocks and general anesthesia (GA), especially when the blocks
were performed in advance of the painful stimulus, favorably influenced
postoperative recovery compared with GA alone. Crile concluded that
“patients given inhalational anesthesia still need to be protected by
regional anesthesia otherwise they might incur persistent central nervous
system changes and enhanced postoperative pain.”2 The
notion that the CNS “modulates” afferent pain signals before being
perceived by the individual was furthered in 1965 when Melzack and Wall
proposed their gate theory.3 This landmark paper suggested
that incoming pain signals are subject to inhibition by either competing
nonpainful afferent input at the same spinal level or from supraspinal
descending pathways. For example, rubbing one's foot after stubbing your toe
lessens the perception of pain due to the “closure” of a theoretical gate
in the substantia gelatinosa that allows for only one type of afferent
impulse to be transmitted to the CNS. However, this theory did not
incorporate long-term changes in the CNS following nociceptive input and to
other external factors that impinge on the individual. It is now recognized
that nociceptor function is dynamic and may be altered following tissue
injury. Repetitive stimulation of small-diameter primary afferent fibers
generates a progressive increase in action potential discharge and increased
excitability of both peripheral and CNS neurons, an event termed
sensitization or “wind-up.” This is the mechanism by which pain may be prolonged beyond
the duration normally expected with an acute insult. Furthermore, this
increased excitability in the CNS has the capacity to permanently alter
spinal cord function leading to the development of chronic pain following an
acute injury. Preemptive analgesia has been proposed as a method of
decreasing postoperative pain by the prevention or attenuation of this
wind-up phenomenon.
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Physiology of Central & Peripheral Sensitization
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The perception of pain is not a hard-wired mechanism, wherein stimuli
are always transmitted and processed in an identical manner each time. In
fact the CNS exhibits a great deal of plasticity. The processing of pain
signals is now recognized to be a complex physiologic cascade that involves
dozens of different neurotransmitters and chemical substrates at several
different anatomic locations. Operative procedures produce an initial
afferent barrage of pain signals and generate a secondary inflammatory
response, both of which contribute substantially to postoperative pain. The
signals have the capacity to initiate prolonged changes in both the
peripheral and central nervous system that will lead to the amplification
and prolongation of postoperative pain. Peripheral sensitization, a
reduction in the threshold of nociceptor afferent peripheral terminals, is a
result of inflammation at the site of surgical trauma.4...