512 J.M. Walker and A.G. Hohmann
mechanical, heat, and chemical stimuli. Primary afferents have a unique morphol-
ogy. The cell bodies, which are found in the dorsal root ganglion, lack dendrites
and synapses and are encased in satellite cells that insulate them. The axon bi-
furcates, sending a branch to the spinal cord and branch to the periphery. Hence,
the sensory apparatus is found on an axon terminal, and indeed action potentials
in the peripheral nerve lead to secretion of neurotransmitter at both the periph-
eral and central terminals. The biochemical machinery of nociceptors includes
a variety of molecular transduction elements such as transient receptor potential
(TRP) channels, acid sensing channels, and P2X3 receptors, as well as particular
neurotransmitters including glutamate, substance P, and calcitonin gene-related
peptide (CGRP). On the central terminals are found presynaptic receptors that
modulate neurotransmitter release.
1.2
Ascending Pain Pathways
Upon activation of spinal neurons by nociceptors, information about noxious
stimuli is carried to the brain by ascending pathways. Multiple pathways have been
described (for review see Millan 1999, especially Table 4 therein).
1.2.1
Spinothalamic Tract
The classical ascending pathway (Fig. 1) is the spinothalamic tract, a contralaterally
projecting fiber bundle that ascends in the anterolateral aspect of the spinal white
matter to the ventral posterolateral thalamus with extensive collateralization to
brainstem structures prominent among these being the periaqueductal gray (PAG).
1.2.2
Dorsal Column Visceral Pain Pathway
The dorsal column pathway may be of major importance for visceral pain (Berkley
and Hubscher 1995; Willis et al. 1995). This pathway originates from the visceral
processing circuitry in the gray matter surrounding central canal of the spinal cord
and ascends ipsilaterally in the dorsal columns, the white matter areas adjacent to
the midline on the dorsal aspect of the spinal cord. The putative involvement of
the dorsal column in visceral pain is noteworthy for two reasons, the first being
that it supercedes the classical understanding of the dorsal columns as being the
trajectory for discriminative touch sensations, and second that it provides a new
understanding of complex neural pathways for visceral compared to somatosen-
sory pain. Rather than operating in isolation, the dorsal column and spinal routes
cooperate to produce the many perceptions of touch and pain (Berkley and Hub-
scher 1995). This ensemble view encourages the development of novel, integrative
pharmacotherapies and treatments (Berkley and Hubscher 1995).