Ascending Projection Systems

Cells of Origin

STT cells have been identified in various mammals by using anatomical tracers that label neuronal cell bodies by retrograde transport from the thalamus ( , ). Comparable evidence was obtained in humans by examining chromatolytic spinal cells in autopsy material subsequent to cordotomy in terminal patients ( ). The STT is not a monolithic pathway; it originates in three distinct regions of the spinal gray matter ( Fig. 12-1 ):

• 1.

  The most superficial layer of the dorsal horn, called the marginal zone, or lamina I

• 2.

  The deep dorsal horn, or laminae IV–V

• 3.

  The intermediate zone and medial ventral horn, or laminae VII–VIII

Although minor differences exist between species, in primates almost half of STT cells are located in lamina I, about one-quarter are found in laminae IV–V, and the remaining quarter are in laminae VII–VIII. Approximately 85–90% of STT cells are found on the contralateral side, with 10–15% on the ipsilateral side. There are approximately 10,000 STT cells that project to the thalamus from one side. STT cells are most numerous in the cervical and lumbosacral enlargements. Another large population of STT cells is widely distributed bilaterally throughout the C1–2 segments.

Each of the three main populations of STT neurons is dominated by afferent input from a different constellation of primary afferent fibers. Accordingly, these populations of STT cells display different patterns of functional activity. This evidence is based on microelectrode recordings of single STT cells identified by antidromic activation from their axonal terminations in the thalamus.

Lamina I STT Cells

Lamina I cells, which are medium-sized neurons in the most superficial layer of the dorsal horn that arborize longitudinally in the horizontal plane, receive input from small-diameter (Aδ and C) primary afferent fibers that innervate all tissues of the body, including skin, muscle, joint, and viscera (and also specialized trigeminal structures). The fundamental role of lamina I seems to be distribution of modality-selective homeostatic afferent activity related to the physiological status of the tissues of the body, which includes specific activity related to pain, temperature, and itch sensations. Based on cutaneous stimulation, three major classes of modality-selective lamina I STT cells are recognized ( ):

• 1.

  Nociceptive-specific (NS) cells, dominated by monosynaptic Aδ-fiber input, have small receptive fields and respond to noxious mechanical or noxious thermal stimuli or both, but not to innocuous stimulation.

• 2.

  Polymodal nociceptive (HPC) cells, dominated by monosynaptic C-fiber input, respond to noxious heat, pinch, and noxious cold. (The first two classes of lamina I cells are associated with sharp [first] pain and burning [second] pain, respectively. These nociceptive cells may also receive convergent input from muscle, joint, or viscera, but there are NS and HPC lamina I cells that also respond selectively to such input.)

• 3.

  Thermoreceptive-specific lamina I STT cells are excited by innocuous cooling and inhibited by warming the skin (COOL cells), or vice versa (WARM cells) ( ).

In addition, there are histamine-selective (ITCH) and mustard oil–selective cells ( ) and cells selectively sensitive to low-threshold C-fiber tactile stimulation ( ). Lamina I cells of the three major classes have distinctive somatodendritic morphologies: NS cells are fusiform neurons (with unmyelinated axons), HPC cells are multipolar neurons, and COOL cells are pyramidal neurons. Each of these three classes forms approximately one-third of the population of lamina I STT cells.

Laminae IV–V Cells

Laminae IV–V cells, which are large neurons in the neck of the dorsal horn that have dorsally and mediolaterally radiating dendrites, receive input primarily from large-diameter (Aβ) fibers from the skin. Many receive monosynaptic input from nociceptive Aδ fibers and polysynaptic input from C fibers from skin, muscle, or viscera. Although some laminae IV–V STT cells respond predominantly to low-threshold (LT) or non-noxious mechanical cutaneous stimuli, such as brushing hair or graded pressure, others respond predominantly to high-threshold (HT) noxious stimuli such as pinch, heat, and deep squeeze—yet most are so-called wide–dynamic range (WDR) nociceptive cells because they respond to both LT and HT stimuli ( , ).

Individual neurons can have a graded discharge from the innocuous into the noxious range, or they may poorly reflect stimulus intensity; however, as a population, these STT cells reflect the “intensive trajectory” of somatic stimulation and apparently serve as cumulative integrators of the entire spectrum of somatic afferent inflow to the dorsal horn ( ). Cells with (polysynaptic) C-fiber input can respond to repetitive C-fiber activation with a “wind up” discharge (i.e., they rapidly increase to a sustained plateau level if the stimulation is delivered at a rate faster than 0.3 Hz). Lamina V STT cells often receive convergent deep and visceral input, and most have large excitatory and inhibitory receptive fields. They are organized musculotopically rather than somatotopically during development by movement-induced patterns of primary afferent activity, and they are intimately involved in motor reflex activity ( ). Evidence indicates that they respond tonically to multijoint limb position ( ), consistent with afferent input from group II slowly adapting muscle afferents ( ). Lamina I cells may also influence the activity of lamina V cells ( , ).

Laminae VII–VIII Cells

Laminae VII–VIII cells, which are very large neurons in the intermediate zone that have widely radiating dendrites ( ), generally receive convergent input from large-diameter skin and deep (muscle, joint) input, as well as other (polysynaptic) input. These complex cells respond to innocuous or noxious stimulation within large, bilateral, or widely separated somatic regions. They can have very large inhibitory fields and can be excited or inhibited by different modes of somatic stimulation, such as proprioceptive or visceral input ( ). These cells are thought to inform higher levels regarding the integrative state of spinal interneuron pools important for locomotion. Cells in the most medial intermediate zone, near the central canal (lamina X), also receive small-diameter visceral input.

Organization of Ascending STT Axons

The axons of STT cells generally cross in the dorsal and ventral spinal commissures to reach the white matter of the contralateral spinal cord within one or two segments rostral to the cells of origin. Ascending STT axons are concentrated in two locations: the middle of the lateral funiculus (the classic “lateral” spinothalamic tract) and the middle of the anterior (ventral) funiculus (the classic “anterior” spinothalamic tract) ( ). These bundles were first observed histologically by using silver stains for degenerating fibers in human autopsy and monkey material following spinal hemisection. report that the lateral STT originates predominantly from lamina I cells and the anterior STT originates from deeper laminae V and VII cells has been confirmed by recent observations. The lateral STT can be visualized with immunohistochemical staining for calbindin (a particular calcium-binding protein), which labels lamina I cells, as well as their terminations in the thalamus. There is considerable individual variability in the precise location and extent of the lateral STT.

The lateral STT is crudely organized somatotopically. The fibers that join the lateral STT at each segment laterally displace the axons ascending from more caudal levels, with the result being that axons from caudal body regions tend to be located more laterally (i.e., superficially) in the white matter whereas those from rostral body regions are located more medially (closer to midline). At the spinomedullary junction, the lateral and anterior STT bundles coalesce in the ventrolateral aspect of the medulla. Trigeminothalamic axons join the medial aspect of the STT at this level. At the caudal end of the pons the STT shifts dorsally and ascends at the lateral aspect of the parabrachial region (the superior cerebellar peduncle) and then occupies a position ventrolateral to the brachium of the inferior colliculus at the lateral aspect of the mesencephalon. The ascending STT axons show weak topographic organization as they ascend in this position to the thalamus.

STT Projection Sites

Based on anterograde tracing experiments in primates and silver-stained degeneration subsequent to cordotomy in humans, it is known that the STT terminates in six distinct regions of the thalamus, which are represented in Figure 12-2 ( , ). Using nomenclature common to the primate brain, these regions are

• 1.

  The posterior portion of the ventral medial nucleus (VMpo)

• 2.

  The ventral posterior nuclei (VPL, VPM, and VPI)

• 3.

  The ventral lateral nucleus (VL)

• 4.

  The central lateral nucleus (CL)

• 5.

  The parafascicular nucleus (Pf)

• 6.

  The ventral caudal portion of the medial dorsal nucleus (MDvc)

These regions are similarly named in the human, but atlases vary significantly ( ). In the human, the VPM and VPL nuclei have been called the internal and external portions of the ventral caudal (Vc) nucleus, and the VPI has been called the parvicellular part of the ventral caudal nuclei (Vcpc). The recently recognized VMpo nucleus ( ), which is located at the posterior–inferior aspect of VP (or Vc) thalamus, was previously included in the caudal VP, the Vc portae, or the posterior complex.