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“Stimuli become adequate as excitants of pain
when they are of such intensity as threatens damage to the skin.”
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The acute activation of small sensory afferent axons by high-intensity
thermal and mechanical stimuli evokes locally organized spinal motor
reflexes (nociceptive reflexes), autonomic responses, and pain behavior
in animals and humans. This effect is mediated by the local encoding
of afferent input at the level of the dorsal horn and the activation
of spinofugal projection neurons. These projection systems travel
both ipsilaterally and contralaterally in the ventrolateral aspect
of the spinal cord, projecting supraspinally into the medulla, mesencephalon,
and diencephalon. Medullary projections serve to activate spinobulbospinal
reflexes that influence autonomic tone. Other projections into the
mesencephalon and thalamus are assumed to contribute to the perceptual
and complex emotive and discriminative components of the pain state.
It is important to appreciate that the encoding by the sensory afferent
and the spinal dorsal horn of the nociceptive stimulus is the first
step in nociceptive processing, and this encoding process contributes properties
that are important to the understanding of the behavioral correlates
of nociception. The following sections consider aspects of the mechanisms
whereby injury leads to an ongoing pain state from the perspective
of the organization of the sensory afferents and the spinal dorsal
horn. Of particular importance is the appreciation that these linkages
have distinct pharmacologies and that these systems can be regulated
to display prominent increases (hyperalgesia) and decreases (analgesia)
in the input-output function.
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Sensory afferents represent the first link between the nervous
system and the peripheral milieu. Whether they are enteroceptive
organs such as viscera or blood vessels, the meninges, deep structures
such as muscle or joint, or the skin, all surfaces are innervated
by axons that transduce the local milieu to generate action potentials
that provide input to the neuraxis. These primary afferent axons
are constituted of the central (root) and peripheral (nerve) projections
and the dorsal root ganglion cell body that is connected to the
root by a sinuous glomerulus. With the exception of several cranial
nerves, all axons have their primary cell body in the dorsal root
ganglia that lie outside of the neuraxis proper.2
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Normal Sensory
Afferent Activity
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Classification
of Sensory Afferents
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These axons
may be classified according to the nature of the peripheral terminals,
their size (large or small), state of myelination (myelinated or
unmyelinated), and, functionally, according to their conduction
velocity (large axons are rapid; small axons are slower) and to
the modality of stimulation that most effectively results in activity
in the associated axon.
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It is important to emphasize that the peripheral afferent terminal
is an exceedingly specialized region. The terminal provides the
transduction properties that convert stimulus of a given modality
into a local sodium channel–mediated depolarization that ...