**6. Pain circuits of the dorsal horn integrate information**

A cross section of a spinal cord reveals morphologically and biochemically distinct layers of gray matter – Laminae of Rexed after the scientist who first described them – that integrate input from a variety of ascending and descending sources (Figure 2) [35]. Each layer forms a functional compartment containing a dense network of primary afferents, secondary projec‐ tion neurons, descending fibers, and interneurons with unique patterns of connectivity. The most superficial layers of the dorsal horn, laminae I and II, receive peripheral input almost exclusively from Aδ and C fibers while Aβ fibers innervate more medial laminae (III-IV)[36]. Lamina V contains wide dynamic range polymodal projection neurons that receive direct input from Aδ and Aβ fibers as well as indirect input from C fibers [36]. Thus, it appears there is both anatomical segregation (laminae I-IV) and integration (laminae V) of painful and nonpainful stimuli at the level of the spinal cord, providing the substrate for distinct pathophy‐ siological mechanisms in the development of neuropathic pain.

Similarly, facilitation also results in a lowered activation threshold in second order neurons, but distinct from potentiation, the molecular changes occur in a nearby dendritic spine rather than the spine receiving the nociceptive input. If the nearby dendritic spine is a silent partner of an Aβ afferent, molecular changes that lower the threshold recruit this primary afferent into nociceptive circuitry resulting in the perception of pain from innocuous stimuli (i.e. allodynia).

Neuropathic Pain: From Mechanism to Clinical Application

http://dx.doi.org/10.5772/55277

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In addition to heterosynaptic strengthening, phenotypic changes or dendritic sprouting of Aβ fibers can lead to the incorporation of low threshold mechanoreceptors into pain circuitry.

**Figure 2. Neuronal architecture of the dorsal horn.** Laminae (represented by numerals I-VI) are morphologically and functionally distinct layers within the gray matter of the spinal cord. Lamina I primarily contains large projection neurons that send processes up the spinal cord towards higher brain regions. Lamina II, in contrast, is more heavily populated with interneurons, many of which supply inhibitory signals to lamina I projection neurons. Lamina V con‐ tains wide dynamic range neurons that receive primary input from multiple sensory modalities. Peripheral afferents project to distinct laminae. While Aδ and C fibers are associated with superficial laminae, Aβ fibers project more medi‐

ally. For a comprehensive review of dorsal horn circuitry see [36].

It should be noted that primary afferents originating from the orofacial region project to the trigeminal nucleus caudalis of the medulla rather than the dorsal horn of the spinal cord [37]. Similar organization, function, and pathophysiological mechanisms are observed in both nuclei, so they will not be considered separately.
