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Traditionally, the opioid analgesics and the nonsteroidal anti-inflammatory
drugs have been the mainstay for primary analgesia. Numerous other
agents, however, are available in our vast pharmacopeia that are
beneficial as primary or adjuvant analgesics, particularly for chronic
nonmalignant pain that is neuropathic in origin. This vast array
of drugs includes the antidepressants, the anticonvulsants, systemic
local anesthetics, psychostimulants, neuroleptics, autonomic drugs,
calcium channel blockers, skeletal muscle relaxants, N-methyl-d-aspartate
(NMDA) receptor antagonists, corticosteroids, capsaicin, cannabinoids,
and various other miscellaneous agents (e.g., tramadol, lithium,
magnesium, neuronal nicotinic acetylcholine receptor ligands, butyl-p-amino benzoate,
bupivacaine microspheres, and SNX-111).
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Classically, the nociceptive pathway consists of a three neuron
chain, dual-ascending system, which can transmit pain signals from
the periphery to the cerebral cortex. The cell bodies for the first-,
second-, and third-order neurons reside in the dorsal root ganglion,
dorsal horn, and thalamus, respectively. The dual-ascending system
runs in parallel and consists of the Aδ and C fibers. The thinly
myelinated Aδ fibers transmit “first pain,” which
tends to be sharp, stinging, and discriminatory in nature. The unmyelinated
C fibers transmit “second pain,” which is more
diffuse, has a persistent burning quality, and carries an affective-motivational
component to it. Injury to this neuronal pathway is believed to
precipitate neuropathic pain. Examples of chronic neuropathic pain
are listed in Table 62-1, and surgical procedures associated with
neuropathic pain are shown in Table 62-2.
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The pathophysiologic mechanisms that theoretically underlie neuropathic
pain are numerous and may involve ectopic impulses, neurogenic inflammation,
changes in protein expression associated with gene-regulated c-fos,
neuropeptide changes, ephaptic connections, sympathetic dysfunction, death
of inhibitory spinal neurons, peripheral and central neuronal sprouting,
central sensitization, and inflammation of nervi nevorum.1 On
physical examination, patients with neuropathic pain classically
display allodynia, hyperalgesia, and hyperpathia.
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Attenuation of nociceptive transmission can be accomplished at
various points along this pain pathway, which includes transduction,
transmission, modulation, and perception. The purpose of this chapter
is to discuss the numerous drugs available to achieve this. The
goal is to tailor the patient’s analgesic regimen by administering
the appropriate drug, in the correct dose, and by the most appropriate
route of administration so as to maximize analgesia and minimize
side effects. Frequently, additive or even synergistic effects can
be obtained by combining different types of drugs. Drug combinations
may allow ...